Publications Search - Abstract View

Title: Indoor wood combustion, carcinogenic exposure and esophageal cancer in southwest Kenya.
Authors: Mwachiro MM,  Pritchett N,  Calafat AM,  Parker RK,  Lando JO,  Murphy G,  Chepkwony R,  Burgert SL,  Abnet CC,  Topazian MD,  White RE,  Dawsey SM,  Etemadi A
Journal: Environ Int
Date: 2021 Jul
Branches: MEB
PubMed ID: 33689906
PMC ID: not available
Abstract: BACKGROUND: Exposure to polycyclic aromatic hydrocarbons (PAHs) is a risk factor for esophageal squamous cell carcinoma (ESCC) in high-incidence areas of China, Iran and Brazil, but PAH assessments have not been conducted in East Africa, another ESCC hot spot. OBJECTIVE: To evaluate demographic or lifestyle factors associated with the PAH biomarker concentrations in the study population, and whether PAH metabolite concentrations showed any associations with esophageal precancerous lesions. METHODS: We recruited a community-based sample of 289 asymptomatic adults from a rural area of Kenya and performed Lugol's chromoendoscopy to detect esophageal squamous dysplasia (ESD); participants completed a questionnaire and provided a spot urine specimen. We analyzed urine for seven hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene at the U.S. National Center for Environmental Health, and compared creatinine-corrected PAH metabolite concentrations with questionnaire data and the presence of ESD. RESULTS: PAH metabolite concentrations among never tobacco users in these rural Kenya residents were 2.4-28.1 times higher than those reported from never tobacco users in Iran, Brazil and the USA. Female sex, cooking indoors, having no post-primary education, and age <50, but not tobacco use, were positively and significantly associated with PAH metabolite concentrations. Almost all participants used wood as cooking fuel. Nine participants had advanced ESD. Adjusted logistic regression showed a significant association between 2-hydroxynaphthalene (OR = 4.19, 95%CI: 1.01-17.47) and advanced ESD. All other PAH metabolites had positive but non-significant associations with advanced ESD. CONCLUSIONS: Urinary PAH metabolite concentrations among never tobacco users are markedly higher in this group from Kenya than in other populations and are associated with indoor cooking with wood on open, unvented stoves. These metabolite concentrations were also associated with the presence of advanced esophageal dysplasia. Our findings underline the importance of assessing alternative cooking conditions to reduce PAH exposure in this population.
Title: A polymorphism in the promoter of FRAS1 is a candidate SNP associated with metastatic prostate cancer.
Authors: Wang V,  Geybels MS,  Jordahl KM,  Gerke T,  Hamid A,  Penney KL,  Markt SC,  Freedman M,  Pomerantz M,  Lee GM,  Rana H,  Börnigen D,  Rebbeck TR,  Huttenhower C,  Eeles RA,  Stanford JL,  Consortium P,  Berndt SI,  Claessens F,  Sørensen KD,  Park JY,  Vega A,  Usmani N,  Mucci L,  Sweeney CJ
Journal: Prostate
Date: 2021 Jul
Branches: OEEB
PubMed ID: 33956343
PMC ID: not available
Abstract: BACKGROUND: Inflammation and one of its mediators, NF-kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer). METHODS: Using a Bayesian approach leveraging NFκB biology with integration of publicly available datasets we used a previously defined genome-wide functional association network specific to NFκB and lethal prostate cancer. A dense-module-searching method identified modules enriched with significant genes from a genome-wide association study (GWAS) study in a discovery data set, Physicians' Health Study and Health Professionals Follow-up Study (PHS/HPFS). The top 48 candidate single nucleotide polymorphisms (SNPs) from the dense-module-searching method were then assessed in an independent prostate cancer cohort and the one SNP reproducibly associated with lethality was tested in a third cohort. Logistic regression models evaluated the association between each SNP and lethal prostate cancer. The candidate SNP was assessed for association with lethal prostate cancer in 6 of 28 studies in the prostate cancer association group to investigate cancer associated alterations in the genome (PRACTICAL) Consortium where there was some medical record review for death ascertainment which also had SNP data from the ONCOARRAY platform. All men self-identified as Caucasian. RESULTS: The rs1910301 SNP which was reproducibly associated with lethal disease was nominally associated with lethal disease (odds ratio [OR] = 1.40; p = .02) in the discovery cohort and the minor allele was also associated with lethal disease in two independent cohorts (OR = 1.35; p = .04 and OR = 1.35; p = .07). Fixed effects meta-analysis of all three cohorts found an association: OR = 1.37 (95% confidence interval [CI]: 1.15-1.62, p = .0003). This SNP is in the promoter region of FRAS1, a gene involved in epidermal-basement membrane adhesion and is present at a higher frequency in men with African ancestry. No association was found in the subset of studies from the PRACTICAL consortium studies which had a total of 106 deaths out total of 3263 patients and a median follow-up of 4.4 years. CONCLUSIONS: Through its connection with the NFκB pathway, a candidate SNP with a higher frequency in men of African ancestry without cancer was found to be associated with lethal prostate cancer across three well-annotated independent cohorts of Caucasian men.
Title: Utility of interim blood tests for cancer screening in Li-Fraumeni syndrome.
Authors: Oba L,  Best AF,  Mai PL,  Achatz MI,  Albert PS,  Savage SA,  Khincha PP
Journal: Fam Cancer
Date: 2021 Jun 2
Branches: BB, CGB, OD
PubMed ID: 34076823
PMC ID: not available
Abstract: Comprehensive annual screening reduces cancer-related mortality in Li-Fraumeni syndrome (LFS), a cancer-prone disorder caused by pathogenic germline TP53 variants. Blood tests at months 4 and 8 between annual screening are recommended but their effectiveness in early cancer detection has not been established. Interim blood counts and inflammatory biomarkers were evaluated in 132 individuals with LFS (112 adults, 87 female, median age 36 years [range 3-68], median follow-up 37 months [range 2-70]) and test abnormalities were observed in 225 (35%). Thirteen cancers in 12 individuals were diagnosed between annual screenings but only one cancer (colorectal adenocarcinoma) was diagnosed due to an abnormal interim blood test. Fisher's exact test and generalized estimating equation models found no statistical associations between cancer diagnoses and any test abnormality. Four- and 8-monthly interim screening blood tests may not be of independent benefit for cancer detection in LFS, but annual cancer screening and personalized follow-up remain essential.
Title: Tobacco Smoking and Risk of Second Primary Lung Cancer.
Authors: Aredo JV,  Luo SJ,  Gardner RM,  Sanyal N,  Choi E,  Hickey TP,  Riley TL,  Huang WY,  Kurian AW,  Leung AN,  Wilkens LR,  Robbins HA,  Riboli E,  Kaaks R,  Tjønneland A,  Vermeulen RCH,  Panico S,  Le Marchand L,  Amos CI,  Hung RJ,  Freedman ND,  Johansson M,  Cheng I,  Wakelee HA,  Han SS
Journal: J Thorac Oncol
Date: 2021 Jun
Branches: MEB
PubMed ID: 33722709
PMC ID: PMC8159872
Abstract: INTRODUCTION: Lung cancer survivors are at high risk of developing a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined the risk factors for SPLC across multiple epidemiologic cohorts and evaluated the impact of smoking cessation on reducing SPLC risk. METHODS: We analyzed data from 7059 participants in the Multiethnic Cohort (MEC) diagnosed with an initial primary lung cancer (IPLC) between 1993 and 2017. Cause-specific proportional hazards models estimated SPLC risk. We conducted validation studies using the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (N = 3423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (N = 4731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta-analysis. RESULTS: Overall, 163 MEC cases (2.3%) developed SPLC. Smoking pack-years (hazard ratio [HR] = 1.18 per 10 pack-years, p < 0.001) and smoking intensity (HR = 1.30 per 10 cigarettes per day, p < 0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force's screening criteria at IPLC diagnosis also had an increased SPLC risk (HR = 1.92; p < 0.001). Validation studies with the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and European Prospective Investigation into Cancer and Nutrition revealed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (pmeta < 0.001), 1.25 per 10 cigarettes per day (pmeta < 0.001), and 1.99 (pmeta < 0.001) for meeting the U.S. Preventive Services Task Force's criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR = 0.17; p < 0.001). CONCLUSIONS: Tobacco smoking is a risk factor for SPLC. Smoking cessation may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted.
Title: Genetically Inferred Telomere Length and Testicular Germ Cell Tumor Risk.
Authors: Brown DW,  Lan Q,  Rothman N,  Pluta J,  Almstrup K,  Dalgaard MD,  Greene MH,  Grotmol T,  Loveday C,  Schwartz SM,  Turnbull C,  Wiklund F,  Kanetsky PA,  Nathanson KL,  McGlynn KA,  Machiela MJ,  Testicular Cancer Consortium
Journal: Cancer Epidemiol Biomarkers Prev
Date: 2021 Jun
Branches: CGB, ITEB, MEB, OEEB
PubMed ID: 33737296
PMC ID: not available
Abstract: BACKGROUND: Studies evaluating the association between peripheral blood leukocyte telomere length (LTL) and testicular germ cell tumor (TGCT) risk have produced conflicting results. METHODS: Using available genotype data from the Testicular Cancer Consortium (TECAC), polygenic risk score and Mendelian randomization analyses of genetic variants previously associated with LTL were used to assess potential etiologic associations between telomere length and TGCT risk. RESULTS: Genetically inferred telomere length was not associated with TGCT risk among 2,049 cases and 6,921 controls with individual-level genotype data (OR, 1.02; 95% confidence interval, 0.97-1.07). Mendelian randomization analyses using summary statistic data further indicated no evidence for an association between telomere length and TGCT risk among all available TECAC participants (3,558 cases and 13,971 controls). CONCLUSIONS: Our analyses in the largest molecular genetic testicular cancer study to date provide no evidence for an association between genetically inferred peripheral blood LTL and TGCT risk. IMPACT: The lack of evidence for an overall association indicates that peripheral blood LTL is likely not a strong biomarker for TGCT risk.
Title: Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study.
Authors: Byrd DA,  Vogtmann E,  Wu Z,  Han Y,  Wan Y,  Clegg-Lamptey JN,  Yarney J,  Wiafe-Addai B,  Wiafe S,  Awuah B,  Ansong D,  Nyarko K,  Hullings AG,  Hua X,  Ahearn T,  Goedert JJ,  Shi J,  Knight R,  Figueroa JD,  Brinton LA,  Garcia-Closas M,  Sinha R
Journal: Int J Cancer
Date: 2021 Jun 1
Branches: BB, CGR, MEB, OD
PubMed ID: 33460452
PMC ID: not available
Abstract: The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray-Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease.
Title: Concentrations of Cotinine and 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol (NNAL) in U.S. Non-Daily Cigarette Smokers.
Authors: Gutiérrez-Torres DS,  Wang L,  Blount BC,  Xia B,  Sosnoff CS,  Shiels MS,  Inoue-Choi M,  Etemadi A,  Freedman ND
Journal: Cancer Epidemiol Biomarkers Prev
Date: 2021 Jun
Branches: IIB, MEB
PubMed ID: 33737303
PMC ID: not available
Abstract: BACKGROUND: Accumulating evidence suggests that non-daily smokers have higher disease and mortality risks than never smokers. Yet, the accuracy of self-reported non-daily cigarette smoking is poorly understood. METHODS: We examined the concordance between self-reported non-daily smoking and serum cotinine in 18,835 adult participants (20 years or older) of the 2007 to 2014 National Health and Nutrition Examination Surveys, in comparison with daily smokers and nonsmokers. We also analyzed concentrations of the urinary biomarker 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) by smoking status. RESULTS: In the study sample, 77.8% (14,660) reported currently not smoking (nonsmokers), 18.3% (3,446) smoked every day (daily smokers), and 3.9% (729) smoked on some days of the past month (non-daily smokers). Just 2.1% of nonsmokers had cotinine concentrations in the active smoking range (>10 ng/mL), compared with 70.4% of non-daily and 98.8% of daily smokers. Non-daily smokers reported smoking a median of 24 cigarettes per month [interquartile range (IQR) = 9-60] and had substantially higher concentrations of NNAL (median = 72.5; IQR = 14.8-211.0 pg/mL) than nonsmokers (median = 0.4; IQR = 0.4-2.1 pg/mL), although lower than daily smokers (median = 294.0; IQR = 148.0-542.0 pg/mL). Among non-daily smokers, concentrations of cotinine and NNAL were positively correlated with days and cigarettes smoked per month (P < 0.001). CONCLUSIONS: We observed excellent concordance between self-reported non-daily cigarette smoking and concentrations of serum cotinine. IMPACT: These results provide evidence for the validity of self-reported non-daily smoking and indicate that non-daily smokers are exposed to substantial concentrations of carcinogenic nitrosamines regardless of the low number of cigarettes they smoke per month.
Title: Additional SNPs improve risk stratification of a polygenic hazard score for prostate cancer.
Authors: Karunamuni RA,  Huynh-Le MP,  Fan CC,  Thompson W,  Eeles RA,  Kote-Jarai Z,  Muir K,  Lophatananon A,  UKGPCS collaborators,  Schleutker J,  Pashayan N,  Batra J,  APCB BioResource (Australian Prostate Cancer BioResource),  Grönberg H,  Walsh EI,  Turner EL,  Lane A,  Martin RM,  Neal DE,  Donovan JL,  Hamdy FC,  Nordestgaard BG,  Tangen CM,  MacInnis RJ,  Wolk A,  Albanes D,  Haiman CA,  Travis RC,  Stanford JL,  Mucci LA,  West CML,  Nielsen SF,  Kibel AS,  Wiklund F,  Cussenot O,  Berndt SI,  Koutros S,  Sørensen KD,  Cybulski C,  Grindedal EM,  Park JY,  Ingles SA,  Maier C,  Hamilton RJ,  Rosenstein BS,  Vega A,  IMPACT Study Steering Committee and Collaborators,  Kogevinas M,  Penney KL,  Teixeira MR,  Brenner H,  John EM,  Kaneva R,  Logothetis CJ,  Neuhausen SL,  Razack A,  Newcomb LF,  Canary PASS Investigators,  Gamulin M,  Usmani N,  Claessens F,  Gago-Dominguez M,  Townsend PA,  Roobol MJ,  Zheng W,  Profile Study Steering Committee,  Mills IG,  Andreassen OA,  Dale AM,  Seibert TM,  PRACTICAL Consortium
Journal: Prostate Cancer Prostatic Dis
Date: 2021 Jun
Branches: MEB, OEEB
PubMed ID: 33420416
PMC ID: PMC8157993
Abstract: BACKGROUND: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). MATERIALS AND METHOD: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy. RESULTS: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer. CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.
Title: Trends in oral contraceptive and intrauterine device use among reproductive-aged women in the US from 1999 to 2017.
Authors: King LA,  Michels KA,  Graubard BI,  Trabert B
Journal: Cancer Causes Control
Date: 2021 Jun
Branches: BB, MEB
PubMed ID: 33689082
PMC ID: not available
Abstract: PURPOSE: Since the 1960s, increasing oral contraceptive (OC) use has mirrored decreasing ovarian cancer incidence. The impact of intrauterine devices (IUDs) on cancer risk is less well established. With improved access and increased options, we must consider how changing usage can affect cancer risks. METHODS: Nationally representative data from the National Health and Nutrition Examination Survey (NHANES, 1999-2016) and the National Survey for Family Growth (NSFG, 2006-2017) were used to evaluate contraceptive use over time in premenopausal women (NHANES n = 13,179; NSFG n = 26,262). Trends were assessed overall and by race, age, pregnancy history, education, and body mass index. RESULTS: The average annual absolute increase in self-reported IUD use was 0.81% (NSFG), while OC use decreased 0.49% in NSFG and 0.47% in NHANES. This represents a significant decrease in OC use in NSFG [annual percent change (APC) - 2.2% (95% CI - 3.4, - 1.0%), p < 0.01]. Trends in OC use varied somewhat by pregnancy history in NHANES (p-interaction = 0.054). In contrast, IUD use increased 6.2% annually [(1.4, 11.2%), p = 0.03] and varied significantly by pregnancy history (p-interaction < 0.01). Nulligravid women increased IUD use 11.0% annually [(2.6, 20.1%), p = 0.02] compared to women with prior pregnancy at 5.2% [(0.4, 10.2%), p = 0.04]. In 2015-2017, IUD use was 76.5% hormonal (71.1, 81.8%) and 22.9% copper (17.4, 28.3%) with greater hormonal IUD use in obese women [89.4%, (82.9, 95.9%)]. CONCLUSION: Increasing IUD use outpaced declining OC use in premenopausal US women. There may be a resulting decreased gynecologic cancer risk as more women gain access to potentially risk-reducing contraceptives.
Title: Endogenous Progestogens and Colorectal Cancer Risk among Postmenopausal Women.
Authors: Michels KA,  Geczik AM,  Bauer DC,  Brinton LA,  Buist DSM,  Cauley JA,  Dallal CM,  Falk RT,  Hue TF,  Lacey JV Jr,  LaCroix AZ,  Tice JA,  Xu X,  Trabert B
Journal: Cancer Epidemiol Biomarkers Prev
Date: 2021 Jun
Branches: MEB
PubMed ID: 33827983
PMC ID: not available
Abstract: BACKGROUND: The role of progestogens in colorectal cancer development is poorly characterized. To address this, our group developed a highly sensitive assay to measure concentrations of seven markers of endogenous progestogen metabolism among postmenopausal women. METHODS: The markers were measured in baseline serum collected from postmenopausal women in a case-cohort study within the breast and bone follow-up to the fracture intervention trial (B∼FIT). We followed women not using exogenous hormones at baseline (1992-1993) for up to 12 years: 187 women with incident colorectal cancer diagnosed during follow-up and a subcohort of 495 women selected on strata of age and clinical center. We used adjusted Cox regression models with robust variance to estimate risk for colorectal cancer [hazard ratios (HR), 95% confidence intervals (CI)]. RESULTS: High concentrations of pregnenolone and progesterone were not associated with colorectal cancer [quintile(Q)5 versus Q1: pregnenolone HR, 0.71, 95% CI, 0.40-1.25; progesterone HR, 1.25; 95% CI, 0.71-2.22]. A trend of increasing risk was suggested, but statistically imprecise across quintiles of 17-hydroxypregnenolone (Q2 to Q5 HRs, 0.75-1.44; Ptrend, 0.06). CONCLUSIONS: We used sensitive and reliable assays to measure multiple circulating markers of progestogen metabolism. Progestogens were generally unassociated with colorectal cancer risk in postmenopausal women. IMPACT: Our findings are consistent with most prior research on circulating endogenous sex hormones, which taken together suggest that sex hormones may not be major drivers of colorectal carcinogenesis in postmenopausal women.
Title: Health-related and cancer risk concerns among siblings of childhood cancer survivors: a report from the Childhood Cancer Survivor Study (CCSS).
Authors: Morales S,  Salehabadi SM,  Srivastava D,  Gibson TM,  Leisenring WM,  Alderfer MA,  Lown EA,  Zeltzer LK,  Armstrong GT,  Krull KR,  Buchbinder D
Journal: J Cancer Surviv
Date: 2021 Jun 1
Branches: REB
PubMed ID: 34075534
PMC ID: not available
Abstract: OBJECTIVE: To characterize the prevalence and predictors of concerns regarding future health and cancer risk among siblings of childhood cancer survivors. METHODS: This study reports longitudinal data (baseline and follow-up) from 3969 adult siblings (median age = 29 [range 18-56] years) of long-term survivors of childhood cancer (median time since diagnosis 19.6 [9.6-33.8] years). Self-reported future health and cancer risk concerns (concerned vs not concerned) were assessed. Demographics and health data reported by both the siblings and their matched cancer survivors were examined as risk factors for health concerns using multivariable logistic regression. RESULTS: Percentage of siblings reporting future health and cancer risk concerns, respectively, decreased across decade of survivors' diagnosis: 1970s (73.3%; 63.9%), 1980s (67.2%; 62.6%), and 1990s (45.7%; 52.3%). Risk factors associated with future health concerns included sibling chronic health conditions (grade 2 Odds Ratio [OR]=1.57, 95% CI: 1.12-2.20; grades 3-4 OR=1.86, 95% CI: 1.18-2.94; compared to less than grade 2). Risk factors associated with future cancer concerns included sibling chronic health conditions (grade 2 OR=1.43, 95% CI: 1.05-1.94; grades 3-4 OR=1.64, 95% CI: 1.09-2.47; compared to less than grade 2). CONCLUSIONS: Sibling concerns regarding future health and cancer have diminished in recent decades. There are subgroups of siblings that are at-risk for future health and cancer risk concerns. IMPLICATIONS FOR CANCER SURVIVORS: Routine screening of concerns in at-risk siblings of survivors of childhood cancer may benefit the siblings of cancer survivors. These individuals may benefit from early interventions during diagnosis and treatment of their siblings.
Title: Genital powder use and risk of uterine cancer: A pooled analysis of prospective studies.
Authors: O'Brien KM,  Tworoger SS,  Harris HR,  Trabert B,  Weinberg CR,  Fortner RT,  D'Aloisio AA,  Kaunitz AM,  Wentzensen N,  Sandler DP
Journal: Int J Cancer
Date: 2021 Jun 1
Branches: CGB, MEB
PubMed ID: 33433939
PMC ID: PMC8106926
Abstract: When powder is applied to the genital area, it has the potential to reach internal reproductive organs and promote carcinogenesis by irritating and inflaming exposed tissues. Although many studies have considered the association between genital powder use and ovarian cancer risk, the relationship between genital powder use and uterine cancer is less well-studied. We pooled data from four large, prospective cohorts (the Nurses' Health Study, the Nurses' Health Study II, the Sister Study and the Women's Health Initiative - Observational Study). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for prespecified confounders. In total, 209 185 women were included, with 37% reporting ever genital powder use. Over a mean 14.5 years of follow-up, 3272 invasive uterine cancers were diagnosed. There was no overall association between ever genital powder use and uterine cancer (HR = 1.01, 95% CI: 0.94-1.09), with little difference observed for frequent (≥1 times/week) vs never use (HR = 1.05, 95% CI: 0.95-1.16; P-for-trend = .46). Long-term use (>20 years; HR = 1.12, 95% CI: 0.96-1.31; P-for-trend = 0.14) was associated with a small, but not statistically significant, increase in risk, compared to never use. There were not clear differences by uterine cancer histologic subtypes or across strata of relevant covariates, including race/ethnicity, follow-up time, menopausal status and body mass index. The results of this large, pooled analysis do not support a relationship between the use of genital powder and uterine cancer, although the positive associations observed for long-term use may merit further consideration.
Title: Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.
Authors: Tsilidis KK,  Papadimitriou N,  Dimou N,  Gill D,  Lewis SJ,  Martin RM,  Murphy N,  Markozannes G,  Zuber V,  Cross AJ,  Burrows K,  Lopez DS,  Key TJ,  Travis RC,  Perez-Cornago A,  Hunter DJ,  van Duijnhoven FJB,  Albanes D,  Arndt V,  Berndt SI,  Bézieau S,  Bishop DT,  Boehm J,  Brenner H,  Burnett-Hartman A,  Campbell PT,  Casey G,  Castellví-Bel S,  Chan AT,  Chang-Claude J,  de la Chapelle A,  Figueiredo JC,  Gallinger SJ,  Giles GG,  Goodman PJ,  Gsur A,  Hampe J,  Hampel H,  Hoffmeister M,  Jenkins MA,  Keku TO,  Kweon SS,  Larsson SC,  Le Marchand L,  Li CI,  Li L,  Lindblom A,  Martín V,  Milne RL,  Moreno V,  Nan H,  Nassir R,  Newcomb PA,  Offit K,  Pharoah PDP,  Platz EA,  Potter JD,  Qi L,  Rennert G,  Sakoda LC,  Schafmayer C,  Slattery ML,  Snetselaar L,  Schenk J,  Thibodeau SN,  Ulrich CM,  Van Guelpen B,  Harlid S,  Visvanathan K,  Vodickova L,  Wang H,  White E,  Wolk A,  Woods MO,  Wu AH,  Zheng W,  Bueno-de-Mesquita B,  Boutron-Ruault MC,  Hughes DJ,  Jakszyn P,  Kühn T,  Palli D,  Riboli E,  Giovannucci EL,  Banbury BL,  Gruber SB,  Peters U,  Gunter MJ
Journal: Am J Clin Nutr
Date: 2021 Jun 1
Branches: MEB, OEEB
PubMed ID: 33740060
PMC ID: not available
Abstract: BACKGROUND: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. OBJECTIVES: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). METHODS: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. RESULTS: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. CONCLUSIONS: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
Title: Gastroesophageal reflux disease: A risk factor for laryngeal squamous cell carcinoma and esophageal squamous cell carcinoma in the NIH-AARP Diet and Health Study cohort.
Authors: Wang SM,  Freedman ND,  Katki HA,  Matthews C,  Graubard BI,  Kahle LL,  Abnet CC
Journal: Cancer
Date: 2021 Jun 1
Branches: BB, MEB
PubMed ID: 33615447
PMC ID: not available
Abstract: BACKGROUND: Prior studies have suggested that gastroesophageal reflux disease (GERD) may be associated with risk of squamous cancers of the larynx and esophagus; however, most of these studies have had methodological limitations or insufficient control for potential confounders. METHODS: We prospectively examined the association between GERD and esophageal adenocarcinoma (EADC), esophageal squamous cell carcinoma (ESCC), and laryngeal squamous cell carcinoma (LSCC) in 490,605 participants of the NIH-AARP Diet and Health Study cohort who were 50-71 years of age at baseline. Exposure to risk factors were obtained from the baseline questionnaire. GERD diagnosis was extracted among eligible participants via linkage to Medicare diagnoses codes and then multiply imputed for non-Medicare-eligible participants. Hazard ratios (HRs) and 95% CIs of GERD were computed using Cox regression. RESULTS: From 1995 to 2011, we accrued 931 cases of EADC, 876 cases of LSCC, and 301 cases of ESCC in this cohort and estimated multivariable-adjusted HRs of 2.23 (95% CI, 1.72-2.90), 1.91 (95% CI, 1.24-2.94), and 1.99 (95% CI, 1.39-2.84) for EADC, LSCC, and ESCC, respectively. The associations were independent of sex, smoking status, alcohol intake, and follow-up time periods. We estimated that among the general population in the United States, 22.04% of people aged 50-71 years suffered from GERD. Using risk factor distributions for the United States from national survey data, 16.92% of LSCC cases and 17.32% of ESCC cases among individuals aged 50-71 years were estimated to be associated with GERD. CONCLUSION: GERD is a common gastrointestinal disorder, but future prospective studies are needed to replicate our findings. If replicated, they may inform clinical surveillance of GERD patients and suggest new avenues for prevention of these malignancies.
Title: Differences in risk factors for molecular subtypes of clear cell renal cell carcinoma.
Authors: Purdue MP,  Rhee J,  Moore L,  Gao X,  Sun X,  Kirk E,  Bencko V,  Janout V,  Mates D,  Zaridze D,  Petruzella S,  Hakimi AA,  Linehan WM,  Chanock SJ,  Brennan P,  Furberg H,  Troester M,  Rothman N
Journal: Int J Cancer
Date: 2021 May 31
Branches: LGS, OD, OEEB
PubMed ID: 34058014
PMC ID: not available
Abstract: The ccA and ccB molecular subtypes of clear cell renal cell carcinoma (ccRCC) have well-characterized prognostic relevance. However, it is not known whether they possess distinct etiologies. We investigated the relationships between these subtypes and RCC risk factors within a case-control study conducted in Eastern Europe. We analyzed risk factor data for ccA (n=144) and ccB (n=106) cases and 1,476 controls through case-only and case-control comparisons to assess risk factor differences across subtypes using logistic and polytomous regression models. We also performed a meta-analysis summarizing case-only results from our study and three patient cohorts. Patients with ccB tumors had poorer survival than those with ccA tumors and were more likely to be male [case-only odds ratio (OR) 2.68, 95% confidence interval (CI) 1.43-5.03]. In case-control analyses, body mass index was significantly associated with ccA tumors (OR 2.45, 95% CI 1.18-5.10 for ≥35 vs. <25 kg/m2 ) but not with ccB tumors (1.52, 0.56-4.12), while trichloroethylene was associated with ccB but not ccA (OR 3.09, 95% CI 1.11-8.65 and 1.25, 0.36-4.39 respectively for ≥1.58 ppm-years vs. unexposed). A polygenic risk score of genetic variants identified from genome-wide association studies was associated with both ccA and, in particular, ccB (OR 1.82, 1.11-2.99 and 2.87, 95% CI 1.64-5.01 respectively for 90th vs. 10th percentile). In a meta-analysis of case-only results including three patient cohorts we still observed the ccB excess for male sex and the ccA excess for obesity. In conclusion, our findings suggest the existence of etiologic heterogeneity across ccRCC molecular subtypes for several risk factors. This article is protected by copyright. All rights reserved.
Title: Rare Germline Variants in Chordoma-Related Genes and Chordoma Susceptibility.
Authors: Yepes S,  Shah NN,  Bai J,  Koka H,  Li C,  Gui S,  McMaster ML,  Xiao Y,  Jones K,  Wang M,  Vogt A,  Zhu B,  Zhu B,  Hutchinson A,  Yeager M,  Hicks B,  Carter B,  Freedman ND,  Beane-Freeman L,  Chanock SJ,  Zhang Y,  Parry DM,  Yang XR,  Goldstein AM
Journal: Cancers (Basel)
Date: 2021 May 30
Branches: BB, CGB, CGR, ITEB, LGS, MEB, OD, OEEB
PubMed ID: 34070849
PMC ID: not available
Abstract: BACKGROUND: Chordoma is a rare bone cancer with an unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have been associated with chordoma susceptibility in familial and sporadic chordoma. However, the genetic susceptibility of chordoma remains largely unknown. In this study, we investigated rare germline genetic variants in genes involved in TBXT/chordoma-related signaling pathways and other biological processes in chordoma patients from North America and China. METHODS: We identified variants that were very rare in general population and internal control datasets and showed evidence for pathogenicity in 265 genes in a whole exome sequencing (WES) dataset of 138 chordoma patients of European ancestry and in a whole genome sequencing (WGS) dataset of 80 Chinese patients with skull base chordoma. RESULTS: Rare and likely pathogenic variants were identified in 32 of 138 European ancestry patients (23%), including genes that are part of notochord development, PI3K/AKT/mTOR, Sonic Hedgehog, SWI/SNF complex and mesoderm development pathways. Rare pathogenic variants in COL2A1, EXT1, PDK1, LRP2, TBXT and TSC2, among others, were also observed in Chinese patients. CONCLUSION: We identified several rare loss-of-function and predicted deleterious missense variants in germline DNA from patients with chordoma, which may influence chordoma predisposition and reflect a complex susceptibility, warranting further investigation in large studies.
Title: Lymphoma and multiple myeloma in cohorts of persons exposed to ionising radiation at a young age.
Authors: Little MP,  Wakeford R,  Zablotska LB,  Borrego D,  Griffin KT,  Allodji RS,  de Vathaire F,  Lee C,  Brenner AV,  Miller JS,  Campbell D,  Sadetzki S,  Doody MM,  Holmberg E,  Lundell M,  Adams MJ,  French B,  Linet MS,  de Gonzalez AB
Journal: Leukemia
Date: 2021 May 28
Branches: REB
PubMed ID: 34050261
PMC ID: not available
Abstract: There is limited evidence that non-leukaemic lymphoid malignancies are radiogenic. As radiation-related cancer risks are generally higher after childhood exposure, we analysed pooled lymphoid neoplasm data in nine cohorts first exposed to external radiation aged <21 years using active bone marrow (ABM) and, where available, lymphoid system doses, and harmonised outcome classification. Relative and absolute risk models were fitted. Years of entry spanned 1916-1981. At the end of follow-up (mean 42.1 years) there were 593 lymphoma (422 non-Hodgkin (NHL), 107 Hodgkin (HL), 64 uncertain subtype), 66 chronic lymphocytic leukaemia (CLL) and 122 multiple myeloma (MM) deaths and incident cases among 143,136 persons, with mean ABM dose 0.14 Gy (range 0-5.95 Gy) and mean age at first exposure 6.93 years. Excess relative risk (ERR) was not significantly increased for lymphoma (ERR/Gy = -0.001; 95% CI: -0.255, 0.279), HL (ERR/Gy = -0.113; 95% CI: -0.669, 0.709), NHL + CLL (ERR/Gy = 0.099; 95% CI: -0.149, 0.433), NHL (ERR/Gy = 0.068; 95% CI: -0.253, 0.421), CLL (ERR/Gy = 0.320; 95% CI: -0.678, 1.712), or MM (ERR/Gy = 0.149; 95% CI: -0.513, 1.063) (all p-trend > 0.4). In six cohorts with estimates of lymphatic tissue dose, borderline significant increased risks (p-trend = 0.02-0.07) were observed for NHL + CLL, NHL, and CLL. Further pooled epidemiological studies are needed with longer follow-up, central outcome review by expert hematopathologists, and assessment of radiation doses to lymphoid tissues.
Title: Sensitivity of Psychosocial Distress Screening to Identify Cancer Patients at Risk for Financial Hardship During Care Delivery.
Authors: Maldonado JA,  Fu S,  Chen YS,  Acquati C,  Yabroff KR,  Banegas MP,  Chang S,  Conti RM,  Checka CM,  Peterson SK,  Advani P,  Ku K,  Jagsi R,  Giordano SH,  Volk RJ,  Shih YT,  Smith GL
Journal: JCO Oncol Pract
Date: 2021 May 27
Branches: REB
PubMed ID: 34043452
PMC ID: not available
Abstract: PURPOSE: Patients with cancer frequently encounter financial hardship, yet systematic strategies to identify at-risk patients are not established in care delivery. We assessed sensitivity of distress-based screening to identify patients with cancer-related financial hardship and associated care delivery outcomes. METHODS: A survey of 225 patients at a large cancer center assessed cancer-related financial hardship (0-10 Likert scale; highest quintile scores ≥ 5 defined severe hardship). Responses were linked to electronic medical records identifying patients' distress screening scores 6 months presurvey (0-10 scale) and outcomes of missed cancer care visits and bad debt charges (unrecovered patient charges) within 6 months postsurvey. A positive screen for distress was defined as score ≥ 4. We analyzed screening test characteristics for identifying severe financial hardship within 6 months and associations between financial hardship and outcomes using logistic models. RESULTS: Although patients with positive distress screens were more likely to report financial hardship (odds ratio [OR], 1.21; 1.08-1.37; P < .001), a positive distress screen was only 48% sensitive and 70% specific for identifying severe financial hardship. Patients with worse financial hardship scores were more likely to miss oncology care visits within 6 months (for every additional point in financial hardship score from 0 to 10, OR, 1.28; 1.12-1.47; P < .001). Of patients with severe hardship, 72% missed oncology visits versus 35% without severe hardship (P = .006). Patients with worse hardship were more likely to incur any bad debt charges within 6 months (OR, 1.32; 1.13-1.54; P < .001). CONCLUSION: Systematic financial hardship screening is needed to help mitigate adverse care delivery outcomes. Existing distress-based screening lacks sensitivity.
Title: Cervical cancer incidence stratified by age in women living with HIV compared with the general population in the United States, 2002-2016.
Authors: Stier EA,  Engels E,  Horner MJ,  Robinson B,  Qiao B,  Hayes J,  Bayakly R,  Anderson BJ,  Gonsalves L,  Pawlish KS,  Zavala D,  Monterosso A,  Shiels MS
Journal: AIDS
Date: 2021 May 27
Branches: IIB
PubMed ID: 34049357
PMC ID: not available
Abstract: OBJECTIVE: Recommendations for the age of initiating screening for cervical cancer in women living with HIV (WLHIV) in the United States have not changed since 1995 when all women (regardless of immune status) were screened for cervical cancer from the age of onset of sexual activity, which often occurs in adolescence. By 2009, recognizing the lack of benefit as well as harms in screening young women, guidelines were revised to initiate cervical cancer screening for the general population at age 21. By comparing cervical cancer incidence in young WLHIV to that of the general population, we assessed the potential for increasing the recommended age of initiating cervical cancer screening in WLHIV. DESIGN: We compared age-specific invasive cervical cancer (ICC) rates among WLHIV to the general population in the United States HIV/AIDS Cancer Match Study. METHODS: We estimated standardized incidence ratios as the observed number of cervical cancer cases among WLHIV divided by the expected number, standardized to the general population by age, race/ethnicity, registry and calendar year. RESULTS: ICC rates among WLHIV were elevated across all age groups between ages 25-54 (SIR=3.80; 95%CI 3.48, 4.15), but there were zero cases among ages <25. CONCLUSIONS: The absence of ICC among WLHIV <25 years supports initiating cervical cancer screening at age 21, rather than adolescence, to prevent cancers in WLHIV at ages with higher risk of ICC.
Title: Bile acid synthesis, modulation, and dementia: A metabolomic, transcriptomic, and pharmacoepidemiologic study.
Authors: Varma VR,  Wang Y,  An Y,  Varma S,  Bilgel M,  Doshi J,  Legido-Quigley C,  Delgado JC,  Oommen AM,  Roberts JA,  Wong DF,  Davatzikos C,  Resnick SM,  Troncoso JC,  Pletnikova O,  O'Brien R,  Hak E,  Baak BN,  Pfeiffer R,  Baloni P,  Mohmoudiandehkordi S,  Nho K,  Kaddurah-Daouk R,  Bennett DA,  Gadalla SM,  Thambisetty M
Journal: PLoS Med
Date: 2021 May
Branches: BB, CGB
PubMed ID: 34043628
PMC ID: not available
Abstract: BACKGROUND: While Alzheimer disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association are unclear. We tested whether dysregulation of cholesterol catabolism, through its conversion to primary bile acids (BAs), was associated with dementia pathogenesis. METHODS AND FINDINGS: We used a 3-step study design to examine the role of the primary BAs, cholic acid (CA), and chenodeoxycholic acid (CDCA) as well as their principal biosynthetic precursor, 7α-hydroxycholesterol (7α-OHC), in dementia. In Step 1, we tested whether serum markers of cholesterol catabolism were associated with brain amyloid accumulation, white matter lesions (WMLs), and brain atrophy. In Step 2, we tested whether exposure to bile acid sequestrants (BAS) was associated with risk of dementia. In Step 3, we examined plausible mechanisms underlying these findings by testing whether brain levels of primary BAs and gene expression of their principal receptors are altered in AD. Step 1: We assayed serum concentrations CA, CDCA, and 7α-OHC and used linear regression and mixed effects models to test their associations with brain amyloid accumulation (N = 141), WMLs, and brain atrophy (N = 134) in the Baltimore Longitudinal Study of Aging (BLSA). The BLSA is an ongoing, community-based cohort study that began in 1958. Participants in the BLSA neuroimaging sample were approximately 46% male with a mean age of 76 years; longitudinal analyses included an average of 2.5 follow-up magnetic resonance imaging (MRI) visits. We used the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 1,666) to validate longitudinal neuroimaging results in BLSA. ADNI is an ongoing, community-based cohort study that began in 2003. Participants were approximately 55% male with a mean age of 74 years; longitudinal analyses included an average of 5.2 follow-up MRI visits. Lower serum concentrations of 7α-OHC, CA, and CDCA were associated with higher brain amyloid deposition (p = 0.041), faster WML accumulation (p = 0.050), and faster brain atrophy mainly (false discovery rate [FDR] p = <0.001-0.013) in males in BLSA. In ADNI, we found a modest sex-specific effect indicating that lower serum concentrations of CA and CDCA were associated with faster brain atrophy (FDR p = 0.049) in males.Step 2: In the Clinical Practice Research Datalink (CPRD) dataset, covering >4 million registrants from general practice clinics in the United Kingdom, we tested whether patients using BAS (BAS users; 3,208 with ≥2 prescriptions), which reduce circulating BAs and increase cholesterol catabolism, had altered dementia risk compared to those on non-statin lipid-modifying therapies (LMT users; 23,483 with ≥2 prescriptions). Patients in the study (BAS/LMT) were approximately 34%/38% male and with a mean age of 65/68 years; follow-up time was 4.7/5.7 years. We found that BAS use was not significantly associated with risk of all-cause dementia (hazard ratio (HR) = 1.03, 95% confidence interval (CI) = 0.72-1.46, p = 0.88) or its subtypes. We found a significant difference between the risk of VaD in males compared to females (p = 0.040) and a significant dose-response relationship between BAS use and risk of VaD (p-trend = 0.045) in males.Step 3: We assayed brain tissue concentrations of CA and CDCA comparing AD and control (CON) samples in the BLSA autopsy cohort (N = 29). Participants in the BLSA autopsy cohort (AD/CON) were approximately 50%/77% male with a mean age of 87/82 years. We analyzed single-cell RNA sequencing (scRNA-Seq) data to compare brain BA receptor gene expression between AD and CON samples from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort (N = 46). ROSMAP is an ongoing, community-based cohort study that began in 1994. Participants (AD/CON) were approximately 56%/36% male with a mean age of 85/85 years. In BLSA, we found that CA and CDCA were detectable in postmortem brain tissue samples and were marginally higher in AD samples compared to CON. In ROSMAP, we found sex-specific differences in altered neuronal gene expression of BA receptors in AD. Study limitations include the small sample sizes in the BLSA cohort and likely inaccuracies in the clinical diagnosis of dementia subtypes in primary care settings. CONCLUSIONS: We combined targeted metabolomics in serum and amyloid positron emission tomography (PET) and MRI of the brain with pharmacoepidemiologic analysis to implicate dysregulation of cholesterol catabolism in dementia pathogenesis. We observed that lower serum BA concentration mainly in males is associated with neuroimaging markers of dementia, and pharmacological lowering of BA levels may be associated with higher risk of VaD in males. We hypothesize that dysregulation of BA signaling pathways in the brain may represent a plausible biologic mechanism underlying these results. Together, our observations suggest a novel mechanism relating abnormalities in cholesterol catabolism to risk of dementia.
Title: Cancer incidence and mortality in the USA Astronaut Corps, 1959-2017.
Authors: Reynolds R,  Little MP,  Day S,  Charvat J,  Blattnig S,  Huff J,  Patel ZS
Journal: Occup Environ Med
Date: 2021 May 26
Branches: REB
PubMed ID: 34039755
PMC ID: not available
Abstract: OBJECTIVES: Cancer incidence and mortality are important outcomes in the surveillance of long-term astronaut health. We compare cancer incidence rates, cancer-specific mortality rates, and cancer case-fatality ratios in US astronauts with those in the US general population. METHODS: We use standardised incidence ratios (SIRs) and standardised mortality ratios (SMRs) to index the incidence and mortality of various cancers against rates in the US general population, from the US astronaut cohort inception in April 1959 through 31 December 2017. We compare the lethality of these cancers using the relative case-fatality ratio. RESULTS: Overall cancer incidence and mortality were slightly lower than expected from national rates with SIR 82 (95% CI 63 to 104) and SMR 72 (95% CI 44 to 111) with a modest 14% reduction in case-fatality ratio. Prostate cancer and melanoma skin cancer had significant increases in incidence, with SIR of 162 (95% CI 109 to 232) and 252 (95% CI 126 to 452), respectively, though only melanoma had a significant increase in mortality, with SMR 508 (95% CI 105 to 1485). Lung cancer had a significant deficit of both cases and deaths, while colon cancer had sizeable (but not significant) reductions in incidence and mortality. CONCLUSIONS: The increase in incidence of melanoma is consistent with that observed in aircraft pilots, suggesting this may be associated with ultraviolet radiation or lifestyle factors rather than any astronaut-specific exposure. Reductions in lung cancer incidence and mortality, and trends towards such reductions in colon cancer, may be explained in part by healthy lifestyle, as well as differential screening among astronauts.
Title: Elevated Alu retroelement copy number among workers exposed to diesel engine exhaust.
Authors: Wong JYY,  Cawthon R,  Dai Y,  Vermeulen R,  Bassig BA,  Hu W,  Duan H,  Niu Y,  Downward GS,  Leng S,  Ji BT,  Fu W,  Xu J,  Meliefste K,  Zhou B,  Yang J,  Ren D,  Ye M,  Jia X,  Meng T,  Bin P,  Hosgood Iii HD,  Silverman DT,  Rothman N,  Zheng Y,  Lan Q
Journal: Occup Environ Med
Date: 2021 May 26
Branches: OEEB
PubMed ID: 34039759
PMC ID: not available
Abstract: BACKGROUND: Millions of workers worldwide are exposed to diesel engine exhaust (DEE), a known genotoxic carcinogen. Alu retroelements are repetitive DNA sequences that can multiply and compromise genomic stability. There is some evidence linking altered Alu repeats to cancer and elevated mortality risks. However, whether Alu repeats are influenced by environmental pollutants is unexplored. In an occupational setting with high DEE exposure levels, we investigated associations with Alu repeat copy number. METHODS: A cross-sectional study of 54 male DEE-exposed workers from an engine testing facility and a comparison group of 55 male unexposed controls was conducted in China. Personal air samples were assessed for elemental carbon, a DEE surrogate, using NIOSH Method 5040. Quantitative PCR (qPCR) was used to measure Alu repeat copy number relative to albumin (Alb) single-gene copy number in leucocyte DNA. The unitless Alu/Alb ratio reflects the average quantity of Alu repeats per cell. Linear regression models adjusted for age and smoking status were used to estimate relations between DEE-exposed workers versus unexposed controls, DEE tertiles (6.1-39.0, 39.1-54.5 and 54.6-107.7 µg/m3) and Alu/Alb ratio. RESULTS: DEE-exposed workers had a higher average Alu/Alb ratio than the unexposed controls (p=0.03). Further, we found a positive exposure-response relationship (p=0.02). The Alu/Alb ratio was highest among workers exposed to the top tertile of DEE versus the unexposed controls (1.12±0.08 SD vs 1.06±0.07 SD, p=0.01). CONCLUSION: Our findings suggest that DEE exposure may contribute to genomic instability. Further investigations of environmental pollutants, Alu copy number and carcinogenesis are warranted.
Title: Joint IARC/NCI International Cancer Seminar Series Report: Expert consensus on future directions for ovarian carcinoma research.
Authors: Virani S,  Baiocchi G,  Bowtell D,  Cabasag CJ,  Cho KR,  Fortner RT,  Fujiwara K,  Kim JW,  Köbel M,  Kurtz JE,  Levine DA,  Menon U,  Norquist BM,  Pharoah PDP,  Sood AK,  Tworoger ST,  Wentzensen N,  Chanock SJ,  Brennan P,  Trabert B
Journal: Carcinogenesis
Date: 2021 May 25
Branches: CGB, LGS, MEB, OD
PubMed ID: 34037709
PMC ID: not available
Abstract: Recently, ovarian cancer research has evolved considerably because of the emerging recognition that rather than a single disease, ovarian carcinomas comprise several different histotypes that vary by etiologic origin, risk factors, molecular profiles, therapeutic approaches, and clinical outcome. Despite significant progress in our understanding of the etiologic heterogeneity of ovarian cancer, as well as important clinical advances, it remains the eighth most frequently diagnosed cancer in women worldwide and the most fatal gynecologic cancer. The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) jointly convened an expert panel on ovarian carcinoma to develop consensus research priorities based on evolving scientific discoveries. Expertise ranged from etiology, prevention, early detection, pathology, model systems, molecular characterization, and treatment/clinical management. This report summarizes the current state of knowledge and highlights expert consensus on future directions to continue advancing etiologic, epidemiologic, and prognostic research on ovarian carcinoma.
Title: ABO genotypes and the risk of esophageal and gastric cancers.
Authors: Chen Y,  Hu N,  Liao L,  Yu K,  Shu XO,  Zheng W,  Yuan JM,  Koh WP,  Qiao YL,  Fan JH,  Dawsey SM,  Freedman ND,  Taylor PR,  Goldstein AM,  Abnet CC
Journal: BMC Cancer
Date: 2021 May 22
Branches: BB, CGB, MEB
PubMed ID: 34022824
PMC ID: PMC8141232
Abstract: BACKGROUND: Blood type has been associated with the risk of gastric cancer, but few studies have examined the association with esophageal squamous cell carcinoma (ESCC). METHODS: We conducted a case-control study using genotyping data of Chinese individuals, including cases of 2022 ESCC, 1189 gastric cardia adenocarcinoma, 1161 gastric noncardia adenocarcinoma, and 2696 controls. Genetic blood type was imputed using three single nucleotide polymorphisms. We used logistic regression to examine the association between blood type and the risk of each cancer. RESULTS: Compared to blood type O, the risk of ESCC was significantly elevated for blood type B and AB, with the highest risk for type AB (OR, 95%CI: 1.34, 1.07-1.67). Analysis of genotype suggested that the association of ESCC was from carrying the B allele. Similarly, blood type was significantly associated with gastric noncardia adenocarcinoma (P < 0.001) with risk significantly elevated in type A (1.37, 1.14-1.65) and AB (1.44, 1.10-1.89) compared to type O. Blood type was not associated with gastric cardia adenocarcinoma (P = 0.13). CONCLUSIONS: This study provides novel insights into the association between blood type and the risk of ESCC and restricted previously observed association to only gastric noncardia cancer, providing important evidence to clarify the pattern of association and suggesting mechanisms of action.
Title: RTEL1 influences the abundance and localization of TERRA RNA.
Authors: Ghisays F,  Garzia A,  Wang H,  Canasto-Chibuque C,  Hohl M,  Savage SA,  Tuschl T,  Petrini JHJ
Journal: Nat Commun
Date: 2021 May 21
Branches: CGB, OD
PubMed ID: 34021146
PMC ID: not available
Abstract: Telomere repeat containing RNAs (TERRAs) are a family of long non-coding RNAs transcribed from the subtelomeric regions of eukaryotic chromosomes. TERRA transcripts can form R-loops at chromosome ends; however the importance of these structures or the regulation of TERRA expression and retention in telomeric R-loops remain unclear. Here, we show that the RTEL1 (Regulator of Telomere Length 1) helicase influences the abundance and localization of TERRA in human cells. Depletion of RTEL1 leads to increased levels of TERRA RNA while reducing TERRA-containing R loops at telomeres. In vitro, RTEL1 shows a strong preference for binding G-quadruplex structures which form in TERRA. This binding is mediated by the C-terminal region of RTEL1, and is independent of the RTEL1 helicase domain. RTEL1 binding to TERRA appears to be essential for cell viability, underscoring the importance of this function. Degradation of TERRA-containing R-loops by overexpression of RNAse H1 partially recapitulates the increased TERRA levels and telomeric instability associated with RTEL1 deficiency. Collectively, these data suggest that regulation of TERRA is a key function of the RTEL1 helicase, and that loss of that function may contribute to the disease phenotypes of patients with RTEL1 mutations.
Title: Gynaecological and reproductive health of women with telomere biology disorders.
Authors: Giri N,  Alter BP,  Savage SA,  Stratton P
Journal: Br J Haematol
Date: 2021 May 21
Branches: CGB, OD
PubMed ID: 34019708
PMC ID: not available
Abstract: Reproductive health may be adversely impacted in women with dyskeratosis congenita (DC) and related telomere biology disorders (TBD). We evaluated gynaecological problems, fertility, and pregnancy outcomes in 39 females aged 10-81 years who were followed longitudinally in our DC/TBD cohort. Twenty-six had bone marrow failure and 12 underwent haematopoietic cell transplantation. All attained menarche at a normal age. Thirteen women reported menorrhagia; ten used hormonal contraception to reduce bleeding. Nine experienced natural normal-aged menopause. Gynaecological problems (endometriosis = 3, pelvic varicosities = 1, cervical intraepithelial neoplasia = 1, and uterine prolapse = 2) resulted in surgical menopause in seven. Twenty-five of 26 women attempting fertility carried 80 pregnancies with 49 (61%) resulting in livebirths. Ten (38%) women experienced 28 (35%) miscarriages, notably recurrent pregnancy loss in five (19%). Preeclampsia (n = 6, 24%) and progressive cytopenias (n = 10, 40%) resulted in maternal-fetal compromise, including preterm (n = 5) and caesarean deliveries (n = 18, 37%). Gynaecological/reproductive problems were noted mainly in women with autosomal-dominant inheritance; others were still young or died early. Although women with TBDs had normal menarche, fertility, and menopause, gynaecological problems and pregnancy complications leading to caesarean section, preterm delivery, or transfusion support were frequent. Women with TBDs will benefit from multidisciplinary, coordinated care by haematology, gynaecology and maternal-fetal medicine.
Title: Associations of circulating choline and its related metabolites with cardiometabolic biomarkers: an international pooled analysis.
Authors: Pan XF,  Yang JJ,  Shu XO,  Moore SC,  Palmer ND,  Guasch-Ferré M,  Herrington DM,  Harada S,  Eliassen H,  Wang TJ,  Gerszten RE,  Albanes D,  Tzoulaki I,  Karaman I,  Elliott P,  Zhu H,  Wagenknecht LE,  Zheng W,  Cai H,  Cai Q,  Matthews CE,  Menni C,  Meyer KA,  Lipworth LP,  Ose J,  Fornage M,  Ulrich CM,  Yu D
Journal: Am J Clin Nutr
Date: 2021 May 21
Branches: MEB
PubMed ID: 34020444
PMC ID: not available
Abstract: BACKGROUND: Choline is an essential nutrient; however, the associations of choline and its related metabolites with cardiometabolic risk remain unclear. OBJECTIVE: We examined the associations of circulating choline, betaine, carnitine, and dimethylglycine (DMG) with cardiometabolic biomarkers and their potential dietary and nondietary determinants. METHODS: The cross-sectional analyses included 32,853 participants from 17 studies, who were free of cancer, cardiovascular diseases, chronic kidney diseases, and inflammatory bowel disease. In each study, metabolites and biomarkers were log-transformed and standardized by means and SDs, and linear regression coefficients (β) and 95% CIs were estimated with adjustments for potential confounders. Study-specific results were combined by random-effects meta-analyses. A false discovery rate <0.05 was considered significant. RESULTS: We observed moderate positive associations of circulating choline, carnitine, and DMG with creatinine [β (95% CI): 0.136 (0.084, 0.188), 0.106 (0.045, 0.168), and 0.128 (0.087, 0.169), respectively, for each SD increase in biomarkers on the log scale], carnitine with triglycerides (β = 0.076; 95% CI: 0.042, 0.109), homocysteine (β = 0.064; 95% CI: 0.033, 0.095), and LDL cholesterol (β = 0.055; 95% CI: 0.013, 0.096), DMG with homocysteine (β = 0.068; 95% CI: 0.023, 0.114), insulin (β = 0.068; 95% CI: 0.043, 0.093), and IL-6 (β = 0.060; 95% CI: 0.027, 0.094), but moderate inverse associations of betaine with triglycerides (β = -0.146; 95% CI: -0.188, -0.104), insulin (β = -0.106; 95% CI: -0.130, -0.082), homocysteine (β = -0.097; 95% CI: -0.149, -0.045), and total cholesterol (β = -0.074; 95% CI: -0.102, -0.047). In the whole pooled population, no dietary factor was associated with circulating choline; red meat intake was associated with circulating carnitine [β = 0.092 (0.042, 0.142) for a 1 serving/d increase], whereas plant protein was associated with circulating betaine [β = 0.249 (0.110, 0.388) for a 5% energy increase]. Demographics, lifestyle, and metabolic disease history showed differential associations with these metabolites. CONCLUSIONS: Circulating choline, carnitine, and DMG were associated with unfavorable cardiometabolic risk profiles, whereas circulating betaine was associated with a favorable cardiometabolic risk profile. Future prospective studies are needed to examine the associations of these metabolites with incident cardiovascular events.
Title: Thoughts on "AIDS and COVID-19: A Tale of Two Pandemics and the Role of Statisticians" by Susan S. Ellenberg and Jeffrey S. Morris.
Authors: Gail MH
Journal: Stat Med
Date: 2021 May 20
Branches: BB
PubMed ID: 33963588
PMC ID: not available
Abstract: Human immunodeficiency virus and Covid-19 (or SARS-CoV-2) differ in their incubation distributions and in their susceptibility to immunologic defense. These features affect our ability to predict the course of these epidemics and to control them.
Title: ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG).
Authors: Miller DT,  Lee K,  Chung WK,  Gordon AS,  Herman GE,  Klein TE,  Stewart DR,  Amendola LM,  Adelman K,  Bale SJ,  Gollob MH,  Harrison SM,  Hershberger RE,  McKelvey K,  Richards CS,  Vlangos CN,  Watson MS,  Martin CL,  ACMG Secondary Findings Working Group
Journal: Genet Med
Date: 2021 May 20
Branches: CGB
PubMed ID: 34012068
PMC ID: not available
Abstract:
Title: Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG).
Authors: Miller DT,  Lee K,  Gordon AS,  Amendola LM,  Adelman K,  Bale SJ,  Chung WK,  Gollob MH,  Harrison SM,  Herman GE,  Hershberger RE,  Klein TE,  McKelvey K,  Richards CS,  Vlangos CN,  Stewart DR,  Watson MS,  Martin CL,  ACMG Secondary Findings Working Group
Journal: Genet Med
Date: 2021 May 20
Branches: CGB
PubMed ID: 34012069
PMC ID: not available
Abstract:
Title: Novel Biomarkers of Habitual Alcohol Intake and Associations with Risk of Pancreatic and Liver Cancers and Liver Disease Mortality.
Authors: Loftfield E,  Stepien M,  Viallon V,  Trijsburg L,  Rothwell JA,  Robinot N,  Biessy C,  Bergdahl IA,  Bodén S,  Schulze MB,  Bergman M,  Weiderpass E,  Schmidt JA,  Zamora-Ros R,  Nøst TH,  Sandanger TM,  Sonestedt E,  Ohlsson B,  Katzke V,  Kaaks R,  Ricceri F,  Tjønneland A,  Dahm CC,  Sánchez MJ,  Trichopoulou A,  Tumino R,  Chirlaque MD,  Masala G,  Ardanaz E,  Vermeulen R,  Brennan P,  Albanes D,  Weinstein SJ,  Scalbert A,  Freedman ND,  Gunter MJ,  Jenab M,  Sinha R,  Keski-Rahkonen P,  Ferrari P
Journal: J Natl Cancer Inst
Date: 2021 May 19
Branches: MEB
PubMed ID: 34010397
PMC ID: not available
Abstract: BACKGROUND: Alcohol is an established risk factor for several cancers, but modest alcohol-cancer associations may be missed due to measurement error in self-reported assessments. Biomarkers of habitual alcohol intake may provide novel insight into the relationship between alcohol and cancer risk. METHODS: Untargeted metabolomics was used to identify metabolites correlated with self-reported habitual alcohol intake in a discovery dataset from the European Prospective Investigation into Cancer and Nutrition (EPIC; n = 454). Statistically significant correlations were tested in independent datasets of controls from case-control studies nested within EPIC (n = 280) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC; n = 438) study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of alcohol-associated metabolites and self-reported alcohol intake with risk of pancreatic cancer, hepatocellular carcinoma (HCC), liver cancer, and liver disease mortality in the contributing studies. RESULTS: Two metabolites displayed a dose-response association with self-reported alcohol intake 2-hydroxy-3-methylbutyric acid and an unidentified compound. A 1-SD (log2) increase in levels of 2-hydroxy-3-methylbutyric acid was associated with risk of HCC (OR = 2.54; 95% CI = 1.51-4.27) and pancreatic cancer (OR = 1.43; 95% CI = 1.03-1.99) in EPIC and liver cancer (OR = 2.00; 95% CI = 1.44-2.77) and liver disease mortality (OR = 2.16; 95% CI = 1.63-2.86) in ATBC. Conversely, a 1-SD (log2) increase in questionnaire-derived alcohol intake was not associated with HCC or pancreatic cancer in EPIC or liver cancer in ATBC but was associated with liver disease mortality (OR = 2.19; 95% CI = 1.60-2.98) in ATBC. CONCLUSIONS: 2-Hydroxy-3-methylbutyric acid is a candidate biomarker of habitual alcohol intake that may advance the study of alcohol and cancer risk in population-based studies.
Title: Safety and efficacy of rituximab in Malawi: a case for multicentre oncology clinical trials in Africa?
Authors: Mbulaiteye SM
Journal: Lancet Glob Health
Date: 2021 May 19
Branches: IIB
PubMed ID: 34022151
PMC ID: not available
Abstract:
Title: Simultaneous modeling of detection rate and exposure concentration using semi-continuous models to identify exposure determinants when left-censored data may be a true zero.
Authors: Friesen MC,  Choo-Wosoba H,  Sarazin P,  Hwang J,  Dopart P,  Russ DE,  Deziel NC,  Lavoué J,  Albert PS,  Zhu B
Journal: J Expo Sci Environ Epidemiol
Date: 2021 May 18
Branches: BB, OEEB
PubMed ID: 34006962
PMC ID: not available
Abstract: BACKGROUND: Most methods for treating left-censored data assume the analyte is present but not quantified. Biased estimates may result if the analyte is absent such that the unobserved data represents a mixed exposure distribution with an unknown proportion clustered at zero. OBJECTIVE: We used semi-continuous models to identify time and industry trends in 52,457 OSHA inspection lead sample results. METHOD: The first component of the semi-continuous model predicted the probability of detecting concentrations ≥ 0.007 mg/m3 (highest estimated detection limit, 62% of measurements). The second component predicted the median concentration of measurements ≥ 0.007 mg/m3. Both components included a random-effect for industry and fixed-effects for year, industry group, analytical method, and other variables. We used the two components together to predict median industry- and time-specific lead concentrations. RESULTS: The probabilities of detectable concentrations and the median detected concentrations decreased with year; both were also lower for measurements analyzed for multiple (vs. one) metals and for those analyzed by inductively-coupled plasma (vs. atomic absorption spectroscopy). The covariance was 0.30 (standard error = 0.06), confirming the two components were correlated. SIGNIFICANCE: We identified determinants of exposure in data with over 60% left-censored, while accounting for correlated relationships and without assuming a distribution for the censored data.
Title: Correction: Comparative performance of lung cancer risk models to define lung screening eligibility in the United Kingdom.
Authors: Robbins HA,  Alcala K,  Swerdlow AJ,  Schoemaker MJ,  Wareham N,  Travis RC,  Crosbie PAJ,  Callister M,  Baldwin DR,  Landy R,  Johansson M
Journal: Br J Cancer
Date: 2021 May 17
Branches: CGB
PubMed ID: 34002041
PMC ID: not available
Abstract:
Title: Using lipid profiling to better characterize metabolic differences in apolipoprotein E (APOE) genotype among community-dwelling older Black men.
Authors: Marron MM,  Moore SC,  Wendell SG,  Boudreau RM,  Miljkovic I,  Sekikawa A,  Newman AB
Journal: Geroscience
Date: 2021 May 15
Branches: MEB
PubMed ID: 33991295
PMC ID: not available
Abstract: Apolipoprotein E (APOE) allelic variation is associated with differences in overall circulating lipids and risks of major health outcomes. Lipid profiling provides the opportunity for a more detailed description of lipids that differ by APOE, to potentially inform therapeutic targets for mitigating higher morbidity and mortality associated with certain APOE genotypes. Here, we sought to identify lipids, lipid-like molecules, and important mediators of fatty acid metabolism that differ by APOE among 278 Black men ages 70-81. Using liquid chromatography-mass spectrometry methods, 222 plasma metabolites classified as lipids, lipid-like molecules, or essential in fatty acid metabolism were detected. We applied principal factor analyses to calculate a factor score for each main lipid category. APOE was categorized as ε4 carriers (n = 83; ε3ε4 or ε4ε4), ε2 carriers (n = 58; ε2ε3 or ε2ε2), or ε3 homozygotes (n = 137; ε3ε3). Using analysis of variance, the monoacylglycerol factor, cholesterol ester factor, the factor for triacylglycerols that consist mostly of polyunsaturated fatty acids, sphingosine, and free carnitine significantly differed by APOE (p < 0.05, false discovery rate < 0.30). The monoacylglycerol factor, cholesterol ester factor, and sphingosine were lower, whereas the factor for triacylglycerols that consisted mostly of polyunsaturated fatty acids was higher among ε2 carriers than remaining participants. Free carnitine was lower among ε4 carriers than ε3 homozygotes. Lower monoacylglycerols and cholesteryl esters and higher triacylglycerols that consist mostly of polyunsaturated fatty acids may be protective metabolic characteristics of APOE ε2 carriers, whereas lower carnitine may reflect altered mitochondrial functioning among ε4 carriers in this cohort of older Black men.
Title: Author Correction: A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.
Authors: Coignard J,  Lush M,  Beesley J,  O'Mara TA,  Dennis J,  Tyrer JP,  Barnes DR,  McGuffog L,  Leslie G,  Bolla MK,  Adank MA,  Agata S,  Ahearn T,  Aittomäki K,  Andrulis IL,  Anton-Culver H,  Arndt V,  Arnold N,  Aronson KJ,  Arun BK,  Augustinsson A,  Azzollini J,  Barrowdale D,  Baynes C,  Becher H,  Bermisheva M,  Bernstein L,  Białkowska K,  Blomqvist C,  Bojesen SE,  Bonanni B,  Borg A,  Brauch H,  Brenner H,  Burwinkel B,  Buys SS,  Caldés T,  Caligo MA,  Campa D,  Carter BD,  Castelao JE,  Chang-Claude J,  Chanock SJ,  Chung WK,  Claes KBM,  Clarke CL,  GEMO Study Collaborators,  EMBRACE Collaborators,  Collée JM,  Conroy DM,  Czene K,  Daly MB,  Devilee P,  Diez O,  Ding YC,  Domchek SM,  Dörk T,  Dos-Santos-Silva I,  Dunning AM,  Dwek M,  Eccles DM,  Eliassen AH,  Engel C,  Eriksson M,  Evans DG,  Fasching PA,  Flyger H,  Fostira F,  Friedman E,  Fritschi L,  Frost D,  Gago-Dominguez M,  Gapstur SM,  Garber J,  Garcia-Barberan V,  García-Closas M,  García-Sáenz JA,  Gaudet MM,  Gayther SA,  Gehrig A,  Georgoulias V,  Giles GG,  Godwin AK,  Goldberg MS,  Goldgar DE,  González-Neira A,  Greene MH,  Guénel P,  Haeberle L,  Hahnen E,  Haiman CA,  HÃ¥kansson N,  Hall P,  Hamann U,  Harrington PA,  Hart SN,  He W,  Hogervorst FBL,  Hollestelle A,  Hopper JL,  Horcasitas DJ,  Hulick PJ,  Hunter DJ,  Imyanitov EN,  KConFab Investigators,  HEBON Investigators,  ABCTB Investigators,  Jager A,  Jakubowska A,  James PA,  Jensen UB,  John EM,  Jones ME,  Kaaks R,  Kapoor PM,  Karlan BY,  Keeman R,  Khusnutdinova E,  Kiiski JI,  Ko YD,  Kosma VM,  Kraft P,  Kurian AW,  Laitman Y,  Lambrechts D,  Le Marchand L,  Lester J,  Lesueur F,  Lindstrom T,  Lopez-Fernández A,  Loud JT,  Luccarini C,  Mannermaa A,  Manoukian S,  Margolin S,  Martens JWM,  Mebirouk N,  Meindl A,  Miller A,  Milne RL,  Montagna M,  Nathanson KL,  Neuhausen SL,  Nevanlinna H,  Nielsen FC,  O'Brien KM,  Olopade OI,  Olson JE,  Olsson H,  Osorio A,  Ottini L,  Park-Simon TW,  Parsons MT,  Pedersen IS,  Peshkin B,  Peterlongo P,  Peto J,  Pharoah PDP,  Phillips KA,  Polley EC,  Poppe B,  Presneau N,  Pujana MA,  Punie K,  Radice P,  Rantala J,  Rashid MU,  Rennert G,  Rennert HS,  Robson M,  Romero A,  Rossing M,  Saloustros E,  Sandler DP,  Santella R,  Scheuner MT,  Schmidt MK,  Schmidt G,  Scott C,  Sharma P,  Soucy P,  Southey MC,  Spinelli JJ,  Steinsnyder Z,  Stone J,  Stoppa-Lyonnet D,  Swerdlow A,  Tamimi RM,  Tapper WJ,  Taylor JA,  Terry MB,  Teulé A,  Thull DL,  Tischkowitz M,  Toland AE,  Torres D,  Trainer AH,  Truong T,  Tung N,  Vachon CM,  Vega A,  Vijai J,  Wang Q,  Wappenschmidt B,  Weinberg CR,  Weitzel JN,  Wendt C,  Wolk A,  Yadav S,  Yang XR,  Yannoukakos D,  Zheng W,  Ziogas A,  Zorn KK,  Park SK,  Thomassen M,  Offit K,  Schmutzler RK,  Couch FJ,  Simard J,  Chenevix-Trench G,  Easton DF,  Andrieu N,  Antoniou AC
Journal: Nat Commun
Date: 2021 May 14
Branches: CGB, LGS, OD, TDRP
PubMed ID: 33990587
PMC ID: not available
Abstract: A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-23162-4.
Title: Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident.
Authors: Yeager M,  Machiela MJ,  Kothiyal P,  Dean M,  Bodelon C,  Suman S,  Wang M,  Mirabello L,  Nelson CW,  Zhou W,  Palmer C,  Ballew B,  Colli LM,  Freedman ND,  Dagnall C,  Hutchinson A,  Vij V,  Maruvka Y,  Hatch M,  Illienko I,  Belayev Y,  Nakamura N,  Chumak V,  Bakhanova E,  Belyi D,  Kryuchkov V,  Golovanov I,  Gudzenko N,  Cahoon EK,  Albert P,  Drozdovitch V,  Little MP,  Mabuchi K,  Stewart C,  Getz G,  Bazyka D,  Berrington de Gonzalez A,  Chanock SJ
Journal: Science
Date: 2021 May 14
Branches: BB, CGB, CGR, ITEB, LGS, LTG, MEB, OD, REB, TDRP
PubMed ID: 33888597
PMC ID: not available
Abstract: Effects of radiation exposure from the Chernobyl nuclear accident remain a topic of interest. We investigated germline de novo mutations (DNMs) in children born to parents employed as cleanup workers or exposed to occupational and environmental ionizing radiation after the accident. Whole-genome sequencing of 130 children (born 1987-2002) and their parents did not reveal an increase in the rates, distributions, or types of DNMs relative to the results of previous studies. We find no elevation in total DNMs, regardless of cumulative preconception gonadal paternal [mean = 365 milligrays (mGy), range = 0 to 4080 mGy] or maternal (mean = 19 mGy, range = 0 to 550 mGy) exposure to ionizing radiation. Thus, we conclude that, over this exposure range, evidence is lacking for a substantial effect on germline DNMs in humans, suggesting minimal impact from transgenerational genetic effects.
Title: Conversion factors to derive organ doses for canine subjects undergoing CT examinations.
Authors: Yoon J,  Lee C
Journal: Vet Radiol Ultrasound
Date: 2021 May 14
Branches: REB
PubMed ID: 33987905
PMC ID: not available
Abstract: Although a large number of CT scans are being conducted on small animals, especially in Western countries, little is known of absorbed dose from veterinary CT scans. In the current retrospective analytical study, we estimated the radiation dose delivered to dogs from CT scans with various scan protocols and compared the results with those of human patients. We adopted a total of three computerized canine models with three sizes combined with a computer simulation model of a CT scanner. The eyes of the dog model received the greatest dose, 1.10 mGy/mGy, in the head scan, followed by a brain dose of 0.85 mGy/mGy. In the chest, abdomen-pelvis (AP), chest-abdomen-pelvis, and head-chest-abdomen-pelvis scans, the heart wall (0.93 mGy/mGy), ovaries (0.99 mGy/mGy), lungs (1.12 mGy/mGy), and thyroid (1.23 mGy/mGy) received the greatest organ doses, respectively. The smallest dog model received up to 1.4-fold greater organ doses than the largest dog in both the chest and AP scans. Overall, the medium-size canine model received organ doses comparable to those of the 1-year-old child model in the head scan, the 5-year-old child in chest scan, and the 10-year-old child in AP scan. The organ dose conversion factors derived from this study should help evaluate absorbed dose for canine patients undergoing CT exams.
Title: Racial/ethnic disparities in use of surveillance mammogram among breast cancer survivors: a systematic review.
Authors: Advani P,  Advani S,  Nayak P,  VonVille HM,  Diamond P,  Burnett J,  Brewster AM,  Vernon SW
Journal: J Cancer Surviv
Date: 2021 May 13
Branches: REB
PubMed ID: 33982233
PMC ID: not available
Abstract: BACKGROUND: Increasing number of breast cancer survivors in the USA have led to greater focus on the long-term health outcomes and surveillance care among these women. However limited evidence exists of use of surveillance mammography among breast cancer survivors and how it varies across racial/ethnic groups. METHODS: We conducted a systematic review of the literature to explore disparities in use of surveillance mammogram among women breast cancer survivors by searching for relevant studies published between 2000 and 2020 from Medline (Ovid), PubMed (National Library of Medicine), and PsycINFO (Ovid) bibliographic databases. Two authors independently screened titles, abstracts, and full texts of all articles that reported surveillance mammography use across racial/ethnic groups. Data on study design, screening eligibility, sample size, operational definition, and/or measure of the use of a surveillance mammogram among breast cancer survivors and the association between race/ethnicity and use of a surveillance mammogram were summarized in the evidence tables. RESULTS: We identified 1544 records from the three databases, and 30 studies examined the use of surveillance mammograms among breast cancer survivors across race/ethnic groups. Of these, 21 provided adjusted estimates of racial/ethnic disparities in use of surveillance mammograms, and 15 of these reported statistically significant disparities. In summary, most studies reported that non-white women (mainly Blacks and Hispanics) were less likely to receive a timely surveillance mammogram compared to White. CONCLUSION: This study extends the evidence of racial/ethnic disparities beyond completion of initial treatment by finding similar disparities in receipt of surveillance mammograms among breast cancer survivors. IMPLICATION FOR CANCER SURVIVORS: Our findings identify a need to improve efforts to increase post-treatment use of surveillance mammography among racial/ethnic minority women to reduce these gaps and improve overall clinical and quality of life outcomes.
Title: General population screening for ovarian cancer.
Authors: Hurwitz LM,  Pinsky PF,  Trabert B
Journal: Lancet
Date: 2021 May 12
Branches: MEB, OEEB
PubMed ID: 33991478
PMC ID: not available
Abstract:
Title: Aspirin, ibuprofen, and reduced risk of advanced colorectal adenoma incidence and recurrence and colorectal cancer in the PLCO Cancer Screening Trial.
Authors: Chudy-Onwugaje K,  Huang WY,  Su LJ,  Purdue MP,  Johnson CC,  Wang L,  Katki HA,  Barry KH,  Berndt SI
Journal: Cancer
Date: 2021 May 11
Branches: BB, MEB, OEEB
PubMed ID: 33974712
PMC ID: not available
Abstract: BACKGROUND: Studying the differential impact of aspirin and other nonsteroidal anti-inflammatory drugs across the stages of colorectal neoplasia from early adenoma to cancer is critical for understanding the benefits of these widely used drugs. METHODS: With 13 years of follow-up, the authors prospectively evaluated the association between aspirin and ibuprofen use and incident distal adenoma (1221 cases), recurrent adenoma (862 cases), and incident colorectal cancer (CRC; 2826 cases) among men and women in the population-based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. With multivariable-adjusted models, odds ratio (ORs) and 95% confidence intervals (CIs) for adenoma incidence and recurrence and hazard ratios (HRs) and 95% CIs for incident CRC were determined. RESULTS: The authors observed a significantly reduced risk of incident adenoma with ibuprofen use (≥30 vs <4 pills per month: OR, 0.76 [95% CI, 0.60-0.95]; Ptrend = .04), particularly advanced adenoma (OR, 0.48 [95% CI, 0.28-0.83]; Ptrend = .005). Among those with a previous adenoma detected through screening, aspirin use was associated with a decreased risk of advanced recurrent adenoma (≥30 vs <4 pills per month: OR, 0.56 [95% CI, 0.36-0.87]; Ptrend = 0.006). Both aspirin (HR, 0.88 [95% CI, 0.81-0.96]; Ptrend <.0001) and ibuprofen use (HR, 0.81 [95% CI, 0.70-0.93); Ptrend = 0.003) ≥30 versus <4 pills per month were significantly associated with reduced CRC risk. CONCLUSIONS: In this large prospective study with long-term follow-up, a beneficial role for not only aspirin, but also ibuprofen, in preventing advanced adenoma and curbing progression to recurrence and cancer among older adults was observed.
Title: Pesticide Use and Kidney Function Among Farmers in the Biomarkers of Exposure and Effect in Agriculture Study.
Authors: Shearer JJ,  Sandler DP,  Andreotti G,  Murata K,  Shrestha S,  Parks CG,  Liu D,  Alavanja MC,  Landgren O,  Beane Freeman LE,  Hofmann JN
Journal: Environ Res
Date: 2021 May 11
Branches: BB, OEEB
PubMed ID: 33989625
PMC ID: not available
Abstract: BACKGROUND: Pesticides have been reported to be associated with malignant and non-malignant kidney disease. Few studies have examined the relationship between individual pesticides and kidney dysfunction. OBJECTIVE: We evaluated the associations of pesticide use with measured kidney function among male pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture (BEEA) study, a subcohort in the Agricultural Health Study. METHODS: Serum creatinine was measured in 1,545 BEEA participants and estimated glomerular filtration rate (eGFR) was calculated with the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Using reported information on lifetime use of 41 pesticides, multivariable linear and logistic regression was used to examine associations with eGFR modeled continuously and with CKD (eGFR <60 mL/min/1.73 m2), respectively. Models were adjusted for possible confounding factors related to kidney function and correlated pesticides. RESULTS: Lower eGFR was observed among pesticide applicators who ever used the herbicides pendimethalin (-3.7%, 95% confidence interval (CI): -5.8%, -1.5%), atrazine (-3.7%, 95% CI: -6.9%, -0.4%), and dicamba (-2.8%, 95% CI: -5.3%, -0.2%) compared with never users of each pesticide. Ever use of pendimethalin (odds ratio (OR)=1.6, 95% CI: 1.1, 2.2) and atrazine (OR=1.8, 95% CI: 1.0, 3.0) was also associated with elevated odds of CKD, with an exposure-response association between intensity-weighted lifetime days of pendimethalin use and CKD among active farmers (N=1,302; ptrend=0.04). Atrazine use within the last year was associated with lower eGFR and elevated odds of CKD when compared with never users, and we observed exposure-response associations with intensity-weighted lifetime days among recent users. Use of several other pesticides was associated with higher eGFR. DISCUSSION: These results suggest that two widely used herbicides, pendimethalin and atrazine, may be associated with altered kidney function among pesticide applicators. Our findings for these herbicides are consistent with observed associations with end-stage renal disease in the Agricultural Health Study.
Title: Management of individuals with germline variants in PALB2: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG).
Authors: Tischkowitz M,  Balmaña J,  Foulkes WD,  James P,  Ngeow J,  Schmutzler R,  Voian N,  Wick MJ,  Stewart DR,  Pal T,  ACMG Professional Practice and Guidelines Committee
Journal: Genet Med
Date: 2021 May 11
Branches: CGB
PubMed ID: 33976419
PMC ID: not available
Abstract: PURPOSE: PALB2 germline pathogenic variants are associated with increased breast cancer risk and smaller increased risk of pancreatic and likely ovarian cancer. Resources for health-care professionals managing PALB2 heterozygotes are currently limited. METHODS: A workgroup of experts sought to outline management of PALB2 heterozygotes based on current evidence. Peer-reviewed publications from PubMed were identified to guide recommendations, which arose by consensus and the collective expertise of the authors. RESULTS: PALB2 heterozygotes should be offered BRCA1/2-equivalent breast surveillance. Risk-reducing mastectomy can be considered guided by personalized risk estimates. Pancreatic cancer surveillance should be considered, but ideally as part of a clinical trial. Typically, ovarian cancer surveillance is not recommended, and risk-reducing salpingo-oophorectomy should only rarely be considered before the age of 50. Given the mechanistic similarities, PALB2 heterozygotes should be considered for therapeutic regimens and trials as those for BRCA1/2. CONCLUSION: This guidance is similar to those for BRCA1/2. While the range of the cancer risk estimates overlap with BRCA1/2, point estimates are lower in PALB2 so individualized estimates are important for management decisions. Systematic prospective data collection is needed to determine as yet unanswered questions such as the risk of contralateral breast cancer and survival after cancer diagnosis.
Title: Prediagnostic circulating inflammation-related biomarkers and gastric cancer: A case-cohort study in Japan.
Authors: Camargo MC,  Song M,  Sawada N,  Inoue M,  Shimazu T,  Charvat H,  Pfeiffer RM,  Yamaji T,  Tsugane S,  Rabkin CS
Journal: Cytokine
Date: 2021 May 10
Branches: BB, IIB, MEB
PubMed ID: 33985855
PMC ID: not available
Abstract: Gastric cancer is preceded by a chronic inflammatory process. Circulating levels of inflammation-related markers may reveal molecular pathways contributing to cancer development. Our study evaluated risk associations of gastric cancer with a wide range of systemic soluble inflammation and immune-response proteins. We performed a case-cohort analysis within the JPHC Study II, including a subcohort of 410 participants selected randomly within defined age and sex groups, and 414 individuals with incident gastric cancer. Ninety-two biomarkers were measured in baseline plasma using proximity extension assays. Gastric cancer multivariable hazard ratios were calculated for two to four quantiles used as ordinal variables of each biomarker by Cox proportional hazards regression models with age as the time metric. Of 73 evaluable biomarkers, three (CCL11, CCL20 and IL17C) were associated with increased gastric cancer risk and two (CCL23 and MMP1) with reduced cancer risk (Ptrends < 0.05). However, no association was statistically significant after a false discovery rate correction. This study largely expands the range of inflammation molecules evaluated for gastric cancer risk but failed to identify novel associations with this neoplasia.
Title: Genetically predicted circulating C-reactive protein concentration and colorectal cancer survival: A Mendelian randomization consortium study.
Authors: Hua X,  Dai JY,  Lindström S,  Harrison TA,  Lin Y,  Alberts SR,  Alwers E,  Berndt SI,  Brenner H,  Buchanan DD,  Campbell PT,  Casey G,  Chang-Claude J,  Gallinger S,  Giles GG,  Goldberg RM,  Gunter MJ,  Hoffmeister M,  Jenkins MA,  Joshi AD,  Ma W,  Milne RL,  Murphy N,  Pai RK,  Sakoda LC,  Schoen RE,  Shi Q,  Slattery ML,  Song M,  White E,  Le Marchand L,  Chan AT,  Peters U,  Newcomb PA
Journal: Cancer Epidemiol Biomarkers Prev
Date: 2021 May 10
Branches: OEEB
PubMed ID: 33972368
PMC ID: not available
Abstract: BACKGROUND: A positive association between circulating C-reactive protein (CRP) and colorectal cancer (CRC) survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically-predicted CRP concentrations and CRC-specific survival. METHODS: We used individual-level data for 16,918 eligible CRC cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Due to the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically-predicted CRP concentrations and CRC-specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components. RESULTS: Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to CRC. Genetically-predicted CRP concentration was not associated with CRC-specific survival (HD= -1.15, 95% CI: -2.76 to 0.47 per 100,000 person-years, P =0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location. CONCLUSIONS: Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on CRC-specific survival. IMPACT: Future research evaluating genetically-determined levels of other circulating inflammatory biomarkers (i.e. interleukin-6) with CRC survival outcomes is needed.
Title: 2020 List of human papillomavirus assays Suitable for primary cervical cancer screening.
Authors: Arbyn M,  Simon M,  Peeters E,  Meijer CJLM,  Berkhof J,  Cuschieri K,  Bonde J,  OÅ¡trbenk Valenčak A,  Zhao FH,  Rezhake R,  Gultekin M,  Dillner J,  de Sanjosé S,  Canfell K,  Hillemanns P,  Almonte M,  Xu L,  Wentzensen N,  Poljak M
Journal: Clin Microbiol Infect
Date: 2021 May 8
Branches: CGB
PubMed ID: 33975008
PMC ID: not available
Abstract: BACKGROUND: Only clinically validated HPV assays can be accepted in cervical cancer screening. OBJECTIVES: To update the list of high-risk HPV assays that fulfil the 2009 international validation criteria (Meijer-2009). DATA SOURCES: PubMed/Medline, Embase, Scopus, references from selected studies; published in January 2014-August 2020. STUDY ELIGIBILITY CRITERIA: HPV test validation studies and primary screening studies, involving testing with an index HPV test and a comparator HPV test with reporting of disease outcome (occurrence of histologically confirmed cervical precancer [CIN2+]). METHODS: Overview tables of relative sensitivity and specificity, including non-inferiority statistics and test reproducibility; random-effect meta-analyses of the relative sensitivity and specificity for CIN2+ on index-vs comparator HPV tests. PARTICIPANTS: Women participating in cervical cancer screening. INTERVENTIONS: Testing with an index and a comparator HPV test of clinician-collected cervical specimens and assessment of disease outcome (<CIN2, CIN2+). Comparator HPV assays were HC2, GP5+/6+ PCR-EIA, recommended in validation guidelines, or tests with consistent previous validations. METHODS: Assessment of relative clinical accuracy (including non-inferiority statistics index vs comparator assay) and test reproducibility; random effects meta-analyses of the relative sensitivity and specificity of index vs comparator tests. RESULTS: Seven hrHPV DNA tests consistently fulfilled all validation criteria in multiple studies using predefined test positivity cut-offs (Abbott RealTime High Risk HPV, Anyplex II HPV HR Detection, BD Onclarity HPV Assay, Cobas 4800 HPV Test, HPV-Risk Assay, PapilloCheck HPV-Screening Test and Xpert HPV). Another assay (Alinity m HR HPV Assay) was fully validated in one validation study. The newer Cobas 6800 HPV Test, was validated in two studies against Cobas 4800. Other tests partially fulfilled the international validation criteria (Cervista HPV HR Test, EUROArray HPV, Hybribio's 14 High-Risk HPV, LMNX Genotyping Kit GP HPV, MALDI-TOF, RIATOL qPCR and a number of other in-house developed assays) since the non-inferior accuracy was reached after a posteriori cut-off optimisation, inconsistent accuracy findings in different studies, and/or insufficient reproducibility assessment. The APTIMA HPV Assay targeting E6/E7 mRNA of hrHPV was fully validated in one formal validation study and showed slightly lower pooled sensitivity but higher specificity than the standard comparator tests in seven screening studies. However, the current international validation criteria relate to DNA assays. The additional requirement for longitudinal performance data required for non-DNA based HPV assays was not assessed in this review. CONCLUSIONS: Eleven hrHPV DNA assays fulfil all requirements for use in cervical cancer screening using clinician-collected specimens.
Title: Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.
Authors: Wu Y,  Huang R,  Wang M,  Bernstein L,  Bethea TN,  Chen C,  Chen Y,  Eliassen AH,  Freedman ND,  Gaudet MM,  Gierach GL,  Giles GG,  Krogh V,  Larsson SC,  Liao LM,  McCullough ML,  Miller AB,  Milne RL,  Monroe KR,  Neuhouser ML,  Palmer JR,  Prizment A,  Reynolds P,  Robien K,  Rohan TE,  Sandin S,  Sawada N,  Sieri S,  Sinha R,  Stolzenberg-Solomon RZ,  Tsugane S,  van den Brandt PA,  Visvanathan K,  Weiderpass E,  Wilkens LR,  Willett WC,  Wolk A,  Zeleniuch-Jacquotte A,  Ziegler RG,  Smith-Warner SA
Journal: Am J Clin Nutr
Date: 2021 May 8
Branches: ITEB, MEB, TDRP
PubMed ID: 33964859
PMC ID: not available
Abstract: BACKGROUND: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d). CONCLUSION: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
Title: Circulating trimethylamine N-oxide in association with diet and cardiometabolic biomarkers: an international pooled analysis.
Authors: Yang JJ,  Shu XO,  Herrington DM,  Moore SC,  Meyer KA,  Ose J,  Menni C,  Palmer ND,  Eliassen H,  Harada S,  Tzoulaki I,  Zhu H,  Albanes D,  Wang TJ,  Zheng W,  Cai H,  Ulrich CM,  Guasch-Ferré M,  Karaman I,  Fornage M,  Cai Q,  Matthews CE,  Wagenknecht LE,  Elliott P,  Gerszten RE,  Yu D
Journal: Am J Clin Nutr
Date: 2021 May 8
Branches: MEB
PubMed ID: 33826706
PMC ID: PMC8106754
Abstract: BACKGROUND: Trimethylamine N-oxide (TMAO), a diet-derived, gut microbial-host cometabolite, has been linked to cardiometabolic diseases. However, the relations remain unclear between diet, TMAO, and cardiometabolic health in general populations from different regions and ethnicities. OBJECTIVES: To examine associations of circulating TMAO with dietary and cardiometabolic factors in a pooled analysis of 16 population-based studies from the United States, Europe, and Asia. METHODS: Included were 32,166 adults (16,269 white, 13,293 Asian, 1247 Hispanic/Latino, 1236 black, and 121 others) without cardiovascular disease, cancer, chronic kidney disease, or inflammatory bowel disease. Linear regression coefficients (β) were computed for standardized TMAO with harmonized variables. Study-specific results were combined by random-effects meta-analysis. A false discovery rate <0.10 was considered significant. RESULTS: After adjustment for potential confounders, circulating TMAO was associated with intakes of animal protein and saturated fat (β = 0.124 and 0.058, respectively, for a 5% energy increase) and with shellfish, total fish, eggs, and red meat (β = 0.370, 0.151, 0.081, and 0.056, respectively, for a 1 serving/d increase). Plant protein and nuts showed inverse associations (β = -0.126 for a 5% energy increase from plant protein and -0.123 for a 1 serving/d increase of nuts). Although the animal protein-TMAO association was consistent across populations, fish and shellfish associations were stronger in Asians (β = 0.285 and 0.578), and egg and red meat associations were more prominent in Americans (β = 0.153 and 0.093). Besides, circulating TMAO was positively associated with creatinine (β = 0.131 SD increase in log-TMAO), homocysteine (β = 0.065), insulin (β = 0.048), glycated hemoglobin (β = 0.048), and glucose (β = 0.023), whereas it was inversely associated with HDL cholesterol (β = -0.047) and blood pressure (β = -0.030). Each TMAO-biomarker association remained significant after further adjusting for creatinine and was robust in subgroup/sensitivity analyses. CONCLUSIONS: In an international, consortium-based study, animal protein was consistently associated with increased circulating TMAO, whereas TMAO associations with fish, shellfish, eggs, and red meat varied among populations. The adverse associations of TMAO with certain cardiometabolic biomarkers, independent of renal function, warrant further investigation.
Title: Blood lead levels and lung cancer mortality: An updated analysis of NHANES II and III.
Authors: Rhee J,  Graubard BI,  Purdue MP
Journal: Cancer Med
Date: 2021 May 7
Branches: BB, OEEB
PubMed ID: 33963676
PMC ID: not available
Abstract: Previous analyses within the National Health and Nutrition Examination Survey (NHANES) II and III cycles suggested an association between blood lead levels (BLLs) and lung cancer mortality, although the evidence was limited by small case numbers. To clarify this relationship, we conducted updated analyses of 4,182 and 15,629 participants in NHANES II and III, respectively, (extending follow-up 20 and 8 years) aged ≥20 with BLL measurements and mortality follow-up through 2014. We fit multivariable Cox models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) relating BLLs and lung cancer with adjustment for smoking and other factors. We did not observe an overall association between BLLs and lung cancer after adjustment for smoking (both surveys) and serum cotinine and environmental tobacco smoke exposure (NHANES III), although suggestive associations were observed among women (NHANES II: HR 2.7, 95% CI 0.7, 10.0 for ≥20.0 µg/dl vs. <10.0 µg/dl, Ptrend = 0.07; NHANES III: HR 11.2, 95% CI 2.1, 59.4 for ≥10.0 µg/dl vs. <2.5 µg/dl, Ptrend = 0.04). After stratifying on smoking status, an association with elevated BLLs was observed in NHANES II only among former smokers (HR 3.2, 95% CI 1.3, 8.0 for ≥15 vs. <15 µg/dl) and in NHANES III only among current smokers (HR 1.7, 95% CI 1.1, 2.8 for ≥5 vs. <5 µg/dl). In summary, we found elevated BLLs to be associated with lung cancer mortality among women in both NHANES II and III. Given the absence of an association among non-smokers, we cannot rule out residual confounding as an explanation for our findings.
Title: Interaction between Genetic Risk Scores for reduced pulmonary function and smoking, asthma and endotoxin.
Authors: Sikdar S,  Wyss AB,  Lee MK,  Hoang TT,  Richards M,  Beane Freeman LE,  Parks C,  Thorne PS,  Hankinson JL,  Umbach DM,  Motsinger-Reif A,  London SJ
Journal: Thorax
Date: 2021 May 7
Branches: OEEB
PubMed ID: 33963087
PMC ID: not available
Abstract: RATIONALE: Genome-wide association studies (GWASs) have identified numerous loci associated with lower pulmonary function. Pulmonary function is strongly related to smoking and has also been associated with asthma and dust endotoxin. At the individual SNP level, genome-wide analyses of pulmonary function have not identified appreciable evidence for gene by environment interactions. Genetic Risk Scores (GRSs) may enhance power to identify gene-environment interactions, but studies are few. METHODS: We analysed 2844 individuals of European ancestry with 1000 Genomes imputed GWAS data from a case-control study of adult asthma nested within a US agricultural cohort. Pulmonary function traits were FEV1, FVC and FEV1/FVC. Using data from a recent large meta-analysis of GWAS, we constructed a weighted GRS for each trait by combining the top (p value<5×10-9) genetic variants, after clumping based on distance (±250 kb) and linkage disequilibrium (r2=0.5). We used linear regression, adjusting for relevant covariates, to estimate associations of each trait with its GRS and to assess interactions. RESULTS: Each trait was highly significantly associated with its GRS (all three p values<8.9×10-8). The inverse association of the GRS with FEV1/FVC was stronger for current smokers (pinteraction=0.017) or former smokers (pinteraction=0.064) when compared with never smokers and among asthmatics compared with non-asthmatics (pinteraction=0.053). No significant interactions were observed between any GRS and house dust endotoxin. CONCLUSIONS: Evaluation of interactions using GRSs supports a greater impact of increased genetic susceptibility on reduced pulmonary function in the presence of smoking or asthma.