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Title: Ambient air pollution and incident bladder cancer risk: Updated analysis of the Spanish Bladder Cancer Study.
Authors: Turner MC,  Gracia-Lavedan E,  Cirac M,  Castaño-Vinyals G,  Malats N,  Tardon A,  Garcia-Closas R,  Serra C,  Carrato A,  Jones RR,  Rothman N,  Silverman DT,  Kogevinas M
Journal: Int J Cancer
Date: 2019 Aug 15
Branches: OEEB
PubMed ID: 30653254
PMC ID: not available
Abstract: Although outdoor air pollution and particulate matter in outdoor air have been consistently linked with increased lung cancer risk, the evidence for associations at other cancer sites is limited. Bladder cancer shares several risk factors with lung cancer and some positive associations of ambient air pollution and bladder cancer risk have been observed. This study examined associations of ambient air pollution and bladder cancer risk in the large-scale Spanish Bladder Cancer Study. Estimates of ambient fine particulate matter (PM2.5 ) and nitrogen dioxide (NO2 ) concentrations were assigned to the geocoded participant residence of 938 incident bladder cancer cases and 973 hospital controls based on European multicity land-use regression models. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) for associations of ambient air pollution and bladder cancer risk were estimated using unconditional logistic regression models. Overall, there was no clear association between either ambient PM2.5 (OR per 5.9 μg/m3  = 1.06, 95% CI 0.71-1.60) or NO2 (OR per 14.2 μg/m3  = 0.97, 95% CI 0.84-1.13) concentrations and incident bladder cancer risk. There was no clear evidence for effect modification according to age group, sex, region, education, cigarette smoking status, or pack-years. Results were also similar among more residentially stable participants and in two-pollutant models. Overall, there was no clear evidence for associations of ambient PM2.5 and NO2 concentrations and incident bladder cancer risk. Further research in other large-scale population studies is needed with detailed information on measured or modeled estimates of ambient air pollution concentrations and individual level risk factors.
Title: Postbiliary drainage rates of cholangitis are impacted by procedural technique for patients with supra-ampullary cholangiocarcinoma: A SEER-Medicare analysis.
Authors: Kariya CM,  Wach MM,  Ruff SM,  Ayabe RI,  Lo WM,  Torres MB,  Petrick JL,  McNeel TS,  Davis JL,  McGlynn KA,  Hernandez JM
Journal: J Surg Oncol
Date: 2019 Aug
Branches: MEB
PubMed ID: 31044430
PMC ID: PMC6635029
Abstract: BACKGROUND: The optimal approach to biliary drainage for patients with supra-ampullary cholangiocarcinoma remains undetermined. Violation of sphincter of Oddi results in bacterial colonization of bile ducts and may increase postdrainage infectious complications. We sought to determine if rates of cholangitis are affected by the type of drainage procedure. METHODS: We examined the Surveillance, Epidemiology, and End Results-Medicare linked database from 1991 to 2013 for cholangiocarcinoma. Biliary drainage procedures were categorized as sphincter of Oddi violating (SOV) or sphincter of Oddi preserving (SOP). Patients were stratified by resection. RESULTS: A total of 1914 patients were included in the final analysis. A total of 1264 patients did not undergo a postdrainage resection (SOP 83, SOV 1181) while 650 did undergo a postdrainage resection (SOP 26, SOV 624). For those patients not undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was 19% compared with 34% in the SOV cohort (P = 0.007). For those patients undergoing a postdrainage resection, the rate of cholangitis 90 days after an SOP procedure was less than 42.3% compared with 30% in the SOV cohort (P = 0.66). CONCLUSION: For patients with supra-ampullary cholangiocarcinoma that did not undergo resection, biliary drainage procedures that violated the sphincter of Oddi were associated with increased rates of cholangitis.
Title: Development and Testing of an Integrated Score for Physical Behaviors.
Authors: Keadle SK,  Kravitz ES,  Matthews CE,  Tseng M,  Carroll RJ
Journal: Med Sci Sports Exerc
Date: 2019 Aug
Branches: BB, MEB
PubMed ID: 30817711
PMC ID: PMC6629509
Abstract: PURPOSE: Interest in a variety of physical behaviors (e.g., exercise, sitting time, sleep) in relation to health outcomes creates a need for new statistical approaches to analyze the joint effects of these distinct but inter-related physical behaviors. We developed and tested an integrated physical behavior score (PBS). METHODS: National Institutes of Health-American Association of Retired Persons Diet and Health Study participants (N = 163,016) completed a questionnaire (2004-2006) asking about time spent in five exercise and nonexercise physical activities, two sedentary behaviors (television and nontelevision), and sleep. In half of the sample, we used shape-constrained additive regression to model the relationship between each behavior and survival. Maximum logit scores from each of the eight behavior-survival functions were summed to produce a PBS that was proportionally rescaled to range from 0 to 100. We examined predictive validity of the PBS in the other half-sample using Cox Proportional Hazards models after adjustment for covariates for all-cause and cause-specific mortality. RESULTS: In the testing sample, over an average of 6.6 yr of follow-up, 8732 deaths occurred. We found a strong graded decline in risk of all-cause mortality across quintiles of PBS (Q5 vs Q1 hazard ratio [95% CI] = 0.53 [0.49, 0.57]). Risk estimates for the PBS were higher than any of the components in isolation. Results were similar but stronger for cardiovascular disease (Q5 vs Q1 = 0.42 [0.39, 0.48]) and other mortality (Q5 vs Q1 = 0.42 [0.36, 0.48]). The relationship between PBS and mortality was observed in stratified analyses by median age, sex, body mass index, and health status. CONCLUSIONS: We developed a novel statistical method generated a composite physical behavior that is predictive of mortality outcomes. Future research is needed to test this approach in an independent sample.
Title: Statin use and reduced risk of biliary tract cancers in the UK Clinical Practice Research Datalink.
Authors: Liu Z,  Alsaggaf R,  McGlynn KA,  Anderson LA,  Tsai HT,  Zhu B,  Zhu Y,  Mbulaiteye SM,  Gadalla SM,  Koshiol J
Journal: Gut
Date: 2019 Aug
Branches: BB, CGB, IIB, MEB
PubMed ID: 30448774
PMC ID: PMC6525087
Abstract: OBJECTIVE: To evaluate the association between statin use and risk of biliary tract cancers (BTC). DESIGN: This is a nested case-control study conducted in the UK Clinical Practice Research Datalink. We included cases diagnosed with incident primary BTCs, including cancers of the gall bladder, bile duct (ie, both intrahepatic and extrahepatic cholangiocarcinoma), ampulla of Vater and mixed type, between 1990 and 2017. For each case, we selected five controls who did not develop BTCs at the time of case diagnosis, matched by sex, year of birth, calendar time and years of enrolment in the general practice using incidence density sampling. Exposures were defined as two or more prescription records of statins 1 year prior to BTC diagnosis or control selection. ORs and 95% CIs for associations between statins and BTC overall and by subtypes were estimated using conditional logistic regression, adjusted for relevant confounders. RESULTS: We included 3118 BTC cases and 15 519 cancer-free controls. Current statin use versus non-use was associated with a reduced risk of all BTCs combined (adjusted OR=0.88, 95% CI 0.79 to 0.98). The reduced risks were most pronounced among long-term users, as indicated by increasing number of prescriptions (ptrend=0.016) and cumulative dose of statins (ptrend=0.008). The magnitude of association was similar for statin use and risk of individual types of BTCs. The reduced risk of BTCs associated with a record of current statin use versus non-use was more pronounced among persons with diabetes (adjusted OR=0.72, 95% CI 0.57 to 0.91). Among non-diabetics, the adjusted OR for current statin use versus non-use was 0.91 (95% CI 0.81 to 1.03, pheterogeneity=0.007). CONCLUSION: Compared with non-use of statins, current statin use is associated with 12% lower risk of BTCs; no association found with former statin use. If replicated, particularly in countries with a high incidence of BTCs, our findings could pave the way for evaluating the value of statins for BTC chemoprevention.
Title: Accelerometer and self-reported measures of sedentary behaviour and associations with adiposity in UK youth.
Authors: Noonan RJ,  Christian D,  Boddy LM,  Saint-Maurice PF,  Welk GJ,  Hibbing PR,  Fairclough SJ
Journal: J Sports Sci
Date: 2019 Aug
Branches: MEB
PubMed ID: 30999815
PMC ID: not available
Abstract: This study used accelerometer and self-report measures of overall sedentary time (ST) and screen time behaviours to examine their respective associations with adiposity among UK youth. Participants (Year groups 5, 8, and 10; n=292, 148 girls) wore the SenseWear Armband Mini accelerometer for eight days and completed the Youth Activity Profile, an online report tool designed to estimate physical activity and ST.Stature, body mass and waist circumference were measured to classify adiposity outcomes (overweight/obese and central obesity). One-way between groups ANOVA and adjusted linear, logistic and multinomial logistic regression analyses were conducted. There was a significant main effect of age on total ST across the whole week (F(2, 289)=41.64, p≤0.001). ST increased monotonically across Year 5 (581.09±107.81 min·d-¹), 8 (671.96±112.59 min·d-¹) and 10 (725.80±115.20 min·d-¹), and all pairwise comparisons were significant at p≤0.001. A steep age-related gradient to mobile phone use was present (p≤0.001). ST was positively associated with adiposity outcomes independent of moderate-to-vigorous intensity physical activity (MVPA; p≤0.001). Engaging in >3 hours of video gaming daily was positively associated with central obesity (OR=2.12, p≤0.05) but not after adjustment for MVPA. Results further demonstrate the importance of reducing overall ST to maintain healthy weight status among UK youth.
Title: Incidence of hepatocellular carcinoma among older Americans attributable to hepatitis C and hepatitis B: 2001 through 2013.
Authors: Shiels MS,  Engels EA,  Yanik EL,  McGlynn KA,  Pfeiffer RM,  O'Brien TR
Journal: Cancer
Date: 2019 Aug 1
Branches: BB, IIB, MEB
PubMed ID: 30980394
PMC ID: PMC6625871
Abstract: BACKGROUND: In the United States, incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing in older individuals. Chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) are important causes of HCC; however, the contribution of viral hepatitis to recent trends in HCC incidence among older Americans is unclear. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare linkage (SEER-Medicare) for the years 2001 through 2013 were used to identify HCC cases among individuals aged ≥66 years and Medicare files were used to assess the HCV and HBV status of these HCC cases. Age-standardized incidence rates of HCV-attributable, HBV-attributable, and HCV/HBV-unrelated HCC were estimated overall and by age group, sex, and race/ethnicity. The authors also calculated annual percent changes (APCs) in HCC incidence. RESULTS: Between 2001 and 2013, a total of 15,300 HCC cases occurred in this population. Overall HCC rates increased 43% from 16.3 to 23.3 per 100,000 population (APC, 3.40% per year), whereas HCV-attributable HCC rates nearly doubled from 4.2 to 8.2 per 100,000 population (APC, 5.62% per year). HCC rates increased more slowly for HBV-attributable HCC (1.3 to 1.8 per 100,000 population; APC, 3.17% per year) and HCV/HBV-unrelated HCC (11.3 to 14.1 per 100,000 population; APC, 2.35% per year). The percentage of HCC cases with evidence of HCV infection increased from 25.7% in 2001 through 2004 to 32.3% in 2011 through 2013, whereas the percentage with HBV remained stable at 8%. In 2013, higher rates for both HCV-attributable and HBV-attributable HCC were noted among individuals aged 66 to 75 years, men, and individuals of Asian ancestry. CONCLUSIONS: Among Americans aged ≥66 years, HCC rates increased rapidly between 2001 and 2013. Although HCV-attributable cases contributed substantially to this increase, rates of HBV-attributable and HCV/HBV-unrelated HCC also rose during this period.
Title: Standardizing Analytic Methods and Reporting in Activity Monitor Validation Studies.
Authors: Welk GJ,  Bai Y,  Lee JM,  Godino J,  Saint-Maurice PF,  Carr L
Journal: Med Sci Sports Exerc
Date: 2019 Aug
Branches: MEB
PubMed ID: 30913159
PMC ID: not available
Abstract: INTRODUCTION: A lack of standardization with accelerometry-based monitors has made it hard to advance applications for both research and practice. Resolving these challenges is essential for developing methods for consistent, agnostic reporting of physical activity outcomes from wearable monitors in clinical applications. METHODS: This article reviewed the literature on the methods used to evaluate the validity of contemporary consumer activity monitors. A rationale for focusing on energy expenditure as a key outcome measure in validation studies was provided followed by a summary of the strengths and limitations of different analytical methods. The primary review included 23 recent validation studies that collectively reported energy expenditure estimates from 58 monitors relative to values from appropriate criterion measures. RESULTS: The majority of studies reported weak indicators such as correlation coefficients (87%), but only half (52%) reported the recommended summary statistic of mean absolute percent error needed to evaluate actual individual error. Fewer used appropriate tests of agreement such as equivalence testing (22%). CONCLUSIONS: The use of inappropriate analytic methods and incomplete reporting of outcomes is a major limitation for systematically advancing research with both research grade and consumer-grade activity monitors. Guidelines are provided to standardize analytic methods and reporting in these types of studies to enhance the utility of the devices for clinical mHealth applications.
Title: Breast cancer risk in relation to plasma metabolites among Hispanic and African American women.
Authors: Zhao H,  Shen J,  Moore SC,  Ye Y,  Wu X,  Esteva FJ,  Tripathy D,  Chow WH
Journal: Breast Cancer Res Treat
Date: 2019 Aug
Branches: MEB
PubMed ID: 30771047
PMC ID: PMC6588417
Abstract: PURPOSE: The metabolic etiology of breast cancer has been explored in the past several years using metabolomics. However, most of these studies only included non-Hispanic White individuals. METHODS: To fill this gap, we performed a two-step (discovery and validation) metabolomics profiling in plasma samples from 358 breast cancer patients and 138 healthy controls. All study subjects were either Hispanics or non-Hispanic African Americans. RESULTS: A panel of 14 identified metabolites significantly differed between breast cancer cases and healthy controls in both the discovery and validation sets. Most of these identified metabolites were lipids. In the pathway analysis, citrate cycle (TCA cycle), arginine and proline metabolism, and linoleic acid metabolism pathways were observed, and they significantly differed between breast cancer cases and healthy controls in both sets. From those 14 metabolites, we selected 9 non-correlated metabolites to generate a metabolic risk score. Increased metabolites risk score was associated with a 1.87- and 1.63-fold increased risk of breast cancer in the discovery and validation sets, respectively (Odds ratio (OR) 1.87, 95% Confidence interval (CI) 1.50, 2.32; OR 1.63, 95% CI 1.36, 1.95). CONCLUSIONS: In summary, our study identified metabolic profiles and pathways that significantly differed between breast cancer cases and healthy controls in Hispanic or non-Hispanic African American women. The results from our study might provide new insights on the metabolic etiology of breast cancer.
Title: Quantifying risk stratification provided by diagnostic tests and risk predictions: Comparison to AUC and decision curve analysis.
Authors: Katki HA
Journal: Stat Med
Date: 2019 Jul 20
Branches: BB
PubMed ID: 31037749
PMC ID: not available
Abstract: A property of diagnostic tests and risk models deserving more attention is risk stratification, defined as the ability of a test or model to separate those at high absolute risk of disease from those at low absolute risk. Risk stratification fills a gap between measures of classification (ie, area under the curve (AUC)) that do not require absolute risks and decision analysis that requires not only absolute risks but also subjective specification of costs and utilities. We introduce mean risk stratification (MRS) as the average change in risk of disease (posttest-pretest) revealed by a diagnostic test or risk model dichotomized at a risk threshold. Mean risk stratification is particularly valuable for rare conditions, where AUC can be high but MRS can be low, identifying situations that temper overenthusiasm for screening with the new test/model. We apply MRS to the controversy over who should get testing for mutations in BRCA1/2 that cause high risks of breast and ovarian cancers. To reveal different properties of risk thresholds to refer women for BRCA1/2 testing, we propose an eclectic approach considering MRS and other metrics. The value of MRS is to interpret AUC in the context of BRCA1/2 mutation prevalence, providing a range of risk thresholds at which a risk model is "optimally informative," and to provide insight into why net benefit arrives to its conclusion.
Title: β-Carotene Supplementation and Lung Cancer Incidence in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study: The Role of Tar and Nicotine.
Authors: Middha P,  Weinstein SJ,  Männistö S,  Albanes D,  Mondul AM
Journal: Nicotine Tob Res
Date: 2019 Jul 17
Branches: MEB
PubMed ID: 29889248
PMC ID: not available
Abstract: INTRODUCTION: The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study demonstrated that β-carotene supplementation increases lung cancer incidence in smokers. Further, cigarettes with higher tar and nicotine content are associated with a higher risk of lung cancer. However, no studies have examined whether the increased risk associated with β-carotene supplementation in smokers varies by the tar or nicotine content of cigarettes. METHODS: The ATBC Study was a randomized, double-blind intervention trial conducted in southwest Finland. A total of 29 133 male smokers, aged 50-69 years, were enrolled and randomly assigned to one of four groups (α-tocopherol, β-carotene, both, or placebo). Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of lung cancer risk by β-carotene trial assignment stratified by a priori categories of cigarette tar and nicotine content. RESULTS: The β-carotene supplementation group had significantly higher risk of developing lung cancer in all categories of tar content (yes vs. no β-carotene supplementation-ultralight cigarettes [≤7 mg tar]: HR = 1.31, 95% CI = 0.91 to 1.89; nonfiltered cigarettes [≥21 mg tar]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .91). Similarly, there was no interaction with nicotine content (yes vs. no β-carotene supplementation-ventilated cigarettes [≤0.8 µg nicotine]: HR = 1.23, 95% CI = 0.98 to 1.54; nonfiltered cigarettes [≥1.3 µg nicotine]: HR = 1.22, 95% CI = 0.91 to 1.64; p for interaction = .83). CONCLUSION: These findings support the conclusion that supplementation with β-carotene increases the risk of lung cancer in smokers regardless of the tar or nicotine content of cigarettes smoked. Our data suggest that all smokers should continue to avoid β-carotene supplementation. IMPLICATIONS: Previous studies demonstrated that β-carotene supplementation increases risk of lung cancer in smokers. This study moves the field forward by examining the potential for modification of risk of lung cancer with different levels of tar and nicotine in cigarettes smoked, as interaction with carcinogens in these components of cigarette smoke is hypothesized to be the mechanism by which β-carotene increases risk. Our study provides evidence that the increased risk of lung cancer in smokers who take β-carotene supplements is not dependent upon the tar or nicotine level of cigarettes smoked and suggests that all smokers should continue to avoid β-carotene supplementation.
Title: Reply to: Decreased incidence of Kaposi sarcoma after kidney transplant in Italy and role of mTOR-inhibitors: 1997-2016.
Authors: Cahoon EK,  Engels EA
Journal: Int J Cancer
Date: 2019 Jul 15
Branches: IIB, REB
PubMed ID: 30613965
PMC ID: not available
Abstract:
Title: Cross-sectional associations between healthy eating index and sex steroid hormones in men-National Health and Nutrition Examination Survey 1999-2002.
Authors: Chen Z,  Pestoni G,  McGlynn KA,  Platz EA,  Rohrmann S
Journal: Andrology
Date: 2019 Jul 10
Branches: MEB
PubMed ID: 31293072
PMC ID: not available
Abstract: BACKGROUND: Diet plays an important role in health and is a modifiable risk factor for chronic diseases. In men, sex steroid hormones influence, and are influenced by, a number of health states. Specific dietary patterns have been found to alter sex steroid hormone levels in observational and intervention studies. Thus, we hypothesized that dietary patterns captured by the Healthy Eating Index (HEI) are associated with serum concentrations of sex steroid hormones and sex hormone-binding globulin (SHBG). OBJECTIVES: The objective is investigating the association between HEI and sex steroid hormones and SHBG in a general US population of men. METHODS: We used data on serum sex steroid hormones and SHBG levels, HEI, and other variables collected in the National Health and Nutrition Examination Survey (NHANES), 1999-2002. A total of 550 men >20 years old were included in the analysis. The cross-sectional associations between HEI (from 0 to 100 points, higher score equates to a healthier diet) with natural logarithm transformed concentrations of total and free testosterone, total and free estradiol, and SHBG were evaluated with multivariable linear regression models and adjusted for potential confounders. We also stratified by the body mass index (BMI) and race/ethnicity and tested for interactions. RESULTS: HEI showed a significant inverse association with free estradiol (p = 0.03), but was not associated with total or free testosterone, total estradiol, or SHBG concentrations. Neither BMI nor race/ethnicity statistically significantly modified the association between HEI and sex steroid hormone levels. CONCLUSION: The present cross-sectional analysis in a representative sample of US men showed no consistent association between eating habits, sex steroid hormones, and SHBG. Longitudinal studies are needed to further investigate potential associations.
Title: Prioritized concordance index for hierarchical survival outcomes.
Authors: Cheung LC,  Pan Q,  Hyun N,  Katki HA
Journal: Stat Med
Date: 2019 Jul 10
Branches: BB
PubMed ID: 30957257
PMC ID: not available
Abstract: We propose an extension of Harrell's concordance (C) index to evaluate the prognostic utility of biomarkers for diseases with multiple measurable outcomes that can be prioritized. Our prioritized concordance index measures the probability that, given a random subject pair, the subject with the worst disease status as of a time τ has the higher predicted risk. Our prioritized concordance index uses the same approach as the win ratio, by basing generalized pairwise comparisons on the most severe or clinically important comparable outcome. We use an inverse probability weighting technique to correct for study-specific censoring. Asymptotic properties are derived using U-statistic properties. We apply the prioritized concordance index to two types of disease processes with a rare primary outcome and a more common secondary outcome. Our simulation studies show that when a predictor is predictive of both outcomes, the new concordance index can gain efficiency and power in identifying true prognostic variables compared to using the primary outcome alone. Using the prioritized concordance index, we examine whether novel clinical measures can be useful in predicting risk of type II diabetes in patients with impaired glucose resistance whose disease status can also regress to normal glucose resistance. We also examine the discrimination ability of four published risk models among ever smokers at risk of lung cancer incidence and subsequent death.
Title: Tobacco smoking and trends in histological subtypes of female lung cancer at the Cancer Hospital of the Chinese Academy of Medical Sciences over 13 years.
Authors: Zeng Q,  Vogtmann E,  Jia MM,  Parascandola M,  Li JB,  Wu YL,  Feng QF,  Zou XN
Journal: Thorac Cancer
Date: 2019 Jul 10
Branches: MEB
PubMed ID: 31293059
PMC ID: not available
Abstract: BACKGROUND: Lung cancer is the leading cause of cancer mortality among women in China, and incidence and mortality continue to rise despite the fact that smoking prevalence is very low among Chinese women. AIM: This study investigated tobacco smoking and trends in histological subtypes of female lung cancer in a central cancer hospital in China. METHODS: Demographic, smoking history and histological information on female lung cancer patients diagnosed or treated from 2000 to 2012 was collected from the Cancer Hospital, Chinese Academy of Medical Science (CHCAMS). The classification of histological subtypes and clinical stages were conducted using the ICD-O-3 and Eighth AJCC Cancer Staging Manuals. Time-trends of histological subtypes were analyzed based on annual percentage change (APC). RESULTS: Overall, 5870 female cases of lung cancer were included in the analysis. The number of female lung cancer patients increased from 509 (2000-2002) to 1744 (2011-2012). The most common histological type of lung cancer was adenocarcinoma (ADC) (72.93%), followed by small cell lung cancer (SCLC) (11.06%), squamous cell carcinoma (SCC) (8.38%) and other (7.63%). Among smokers, the proportion of SCC decreased from 40.5% to 23.7% (P = 0.005), while ADC increased from 35.7% to 50.7% (P = 0.009). In non-smokers, ADC increased from 63.1% to 80.6% (P = 0.006) and SCC decreased from 13.6% to 4.5% (P = 0.016). Among SCC cases, smokers made up a larger proportion of early stage (I/II: 47.1%) compared with late stages (III, 34.3%; IV, 18.6%). CONCLUSION: The number of female lung cancer patients has increased in CHCAMS. In both smoking and non-smoking cases, the proportion of adenocarcinoma increased. Squamous cell carcinomas were more likely to be diagnosed in early stages among smokers.
Title: Circulating inflammation markers and colorectal adenoma risk.
Authors: Huang WY,  Berndt SI,  Shiels MS,  Katki HA,  Chaturvedi AK,  Wentzensen N,  Trabert B,  Kemp TJ,  Pinto LA,  Hildesheim A,  Rothman N,  Purdue MP
Journal: Carcinogenesis
Date: 2019 Jul 6
Branches: BB, CGB, IIB, MEB, OEEB
PubMed ID: 30753331
PMC ID: PMC6612053
Abstract: Inflammation is a driver of colorectal neoplasia; however, what particular inflammatory processes play a role in early carcinogenesis are unclear. We compared serum levels of 78 inflammation markers between 171 pathologically confirmed colorectal adenoma cases (including 48 incident cases) and 344 controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used weighted multivariable logistic regression to compute odds ratio (OR) and 95% confidence interval (CI). We found 14 markers associated with risk of adenoma overall; three of these were also associated with incident adenoma: CC-chemokine cysteine motif chemokine ligand 20 (CCL20) [overall adenoma fourth versus first quartile: OR 4.8, 95% CI 2.0-12, Ptrend 0.0007; incident adenoma third versus first tertile: OR 4.6, 95% CI 1.0-22, Ptrend 0.03], growth-related gene oncogene products (GRO) [OR 3.8, 95% CI 1.6-9.3, Ptrend 0.006 and OR 3.6, 95% CI 1.1-12, Ptrend 0.04, respectively] and insulin [OR 2.9, 95% CI 0.8-10, Ptrend 0.05 and OR 7.8, 95% CI 1.3-46, Ptrend 0.03, respectively]. All statistical tests were two-sided. These results provide important new evidence implicating CCL20- and GRO-related pathways in early colorectal carcinogenesis and further support a role for insulin.
Title: Circulating markers of cellular immune activation in pre-diagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3).
Authors: Huang JY,  Larose TL,  Luu HN,  Wang R,  Fanidi A,  Alcala K,  Stevens VL,  Weinstein SJ,  Albanes D,  Caporaso NE,  Purdue MP,  Ziegler RG,  Freedman ND,  Lan Q,  Prentice RL,  Pettinger M,  Thomson CA,  Cai Q,  Wu J,  Blot WJ,  Shu XO,  Zheng W,  Arslan AA,  Zeleniuch-Jacquotte A,  Le Marchand L,  Wilkens LR,  Haiman CA,  Zhang X,  Stampfer MJ,  Han J,  Giles GG,  Hodge AM,  Severi G,  Johansson M,  Grankvist K,  Langhammer A,  Hveem K,  Xiang YB,  Li HL,  Gao YT,  Visvanathan K,  Ueland PM,  Midttun Ø,  Ulvi A,  Buring JE,  Lee IM,  Sesso HD,  Gaziano JM,  Manjer J,  Relton C,  Koh WP,  Brennan P,  Johansson M,  Yuan JM
Journal: Int J Cancer
Date: 2019 Jul 5
Branches: EBP, MEB, OEEB
PubMed ID: 31276202
PMC ID: not available
Abstract: Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA), and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared with the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all Ptrend <0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression. This article is protected by copyright. All rights reserved.
Title: Nut and Peanut Butter Consumption and Mortality in the National Institutes of Health-AARP Diet and Health Study.
Authors: Amba V,  Murphy G,  Etemadi A,  Wang S,  Abnet CC,  Hashemian M
Journal: Nutrients
Date: 2019 Jul 2
Branches: MEB
PubMed ID: 31269682
PMC ID: not available
Abstract: Although previous studies have shown inverse associations between nut consumption and mortality, the associations between nut consumption and less common causes of mortality have not been investigated. Additionally, about 50% of peanut consumption in the US is through peanut butter but the association between peanut butter consumption and mortality has not been thoroughly evaluated. The National Institutes of Health-AARP (NIH-AARP) Diet and Health Study recruited 566,398 individuals aged 50-71 at baseline in 1995-1996. A food-frequency questionnaire was used to evaluate nut and peanut butter consumption. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals for mortality using the non-consumers as reference groups and three categories of consumption. After excluding subjects with chronic diseases at baseline, there were 64,464 deaths with a median follow-up time of 15.5 years. We observed a significant inverse association between nut consumption and overall mortality (HR C4 vs C1 = 0.78, 95% CI = 0.76, 0.81, p ≤ 0.001). Nut consumption was significantly associated with reduced risk of cancer, cardiovascular, respiratory, infectious, renal and liver disease mortality but not with diabetes or Alzheimer's disease mortality. We observed no significant associations between peanut butter consumption and all-cause (HR C4 vs C1 = 1.00, 95% CI = 0.98, 1.04, p = 0.001) and cause-specific mortality. In a middle-aged US population, nut intake was inversely associated with all-cause mortality and certain types of cause-specific mortality. However, peanut butter consumption was not associated with differential mortality.
Title: Importance of both increasing physical activity and reducing sitting time.
Authors: Arem H,  Matthews CE
Journal: Br J Sports Med
Date: 2019 Jul
Branches: MEB
PubMed ID: 29991571
PMC ID: not available
Abstract:
Title: Correction to: Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer.
Authors: Bien SA,  Su YR,  Conti DV,  Harrison TA,  Qu C,  Guo X,  Lu Y,  Albanes D,  Auer PL,  Banbury BL,  Berndt SI,  Bézieau S,  Brenner H,  Buchanan DD,  Caan BJ,  Campbell PT,  Carlson CS,  Chan AT,  Chang-Claude J,  Chen S,  Connolly CM,  Easton DF,  Feskens EJM,  Gallinger S,  Giles GG,  Gunter MJ,  Hampe J,  Huyghe JR,  Hoffmeister M,  Hudson TJ,  Jacobs EJ,  Jenkins MA,  Kampman E,  Kang HM,  Kühn T,  Küry S,  Lejbkowicz F,  Le Marchand L,  Milne RL,  Li L,  Li CI,  Lindblom A,  Lindor NM,  Martín V,  McNeil CE,  Melas M,  Moreno V,  Newcomb PA,  Offit K,  Pharaoh PDP,  Potter JD,  Qu C,  Riboli E,  Rennert G,  Sala N,  Schafmayer C,  Scacheri PC,  Schmit SL,  Severi G,  Slattery ML,  Smith JD,  Trichopoulou A,  Tumino R,  Ulrich CM,  van Duijnhoven FJB,  Van Guelpen B,  Weinstein SJ,  White E,  Wolk A,  Woods MO,  Wu AH,  Abeçasis GR,  Casey G,  Nickerson DA,  Gruber SB,  Hsu L,  Zheng W,  Peters U
Journal: Hum Genet
Date: 2019 Jul
Branches: MEB, OEEB
PubMed ID: 31254090
PMC ID: not available
Abstract: Every author has erroneously been assigned to the affiliation "62". The affiliation 62 belongs to the author Graham Casey.
Title: Case-control investigation of occupational lead exposure and kidney cancer.
Authors: Callahan CL,  Friesen MC,  Locke SJ,  Dopart PJ,  Stewart PA,  Schwartz K,  Ruterbusch JJ,  Graubard BI,  Chow WH,  Rothman N,  Hofmann JN,  Purdue MP
Journal: Occup Environ Med
Date: 2019 Jul
Branches: BB, OEEB
PubMed ID: 30760604
PMC ID: not available
Abstract: OBJECTIVES: Lead is a suspected carcinogen that has been inconsistently associated with kidney cancer. To clarify this relationship, we conducted an analysis of occupational lead exposure within a population-based study of kidney cancer using detailed exposure assessment methods. METHODS: Study participants (1217 cases and 1235 controls), enrolled between 2002 and 2007, provided information on their occupational histories and, for selected lead-related occupations, answered questions regarding workplace tasks, and use of protective equipment. Industrial hygienists used this information to develop several estimates of occupational lead exposure, including probability, duration and cumulative exposure. Unconditional logistic regression was used to compute ORs and 95% CIs for different exposure metrics, with unexposed subjects serving as the reference group. Analyses were also conducted stratifying on several factors, including for subjects of European ancestry only, single nucleotide polymorphisms in ALAD (rs1805313, rs1800435, rs8177796, rs2761016), a gene involved in lead toxicokinetics. RESULTS: In our study, cumulative occupational lead exposure was not associated with kidney cancer (OR 0.9, 95% CI 0.7 to 1.3 for highest quartile vs unexposed; ptrend=0.80). Other lead exposure metrics were similarly null. We observed no evidence of effect modification for the evaluated ALAD variants (subjects of European ancestry only, 662 cases and 561 controls) and most stratifying factors, although lead exposure was associated with increased risk among never smokers. CONCLUSIONS: The findings of this study do not offer clear support for an association between occupational lead exposure and kidney cancer.
Title: Association Between Intake of Red and Processed Meat and Survival in Patients With Colorectal Cancer in a Pooled Analysis.
Authors: Carr PR,  Banbury BL,  Berndt SI,  Campbell PT,  Chang-Claude J,  Hayes RB,  Howard BV,  Jansen L,  Jacobs EJ,  Lane DS,  Nishihara R,  Ogino S,  Phipps AI,  Slattery ML,  Stefanick ML,  Wallace R,  Walter V,  White E,  Wu K,  Peters U,  Chan AT,  Newcomb PA,  Brenner H,  Hoffmeister M
Journal: Clin Gastroenterol Hepatol
Date: 2019 Jul
Branches: OEEB
PubMed ID: 30476588
PMC ID: PMC6533164
Abstract: BACKGROUND & AIMS: Red and processed meat intake is associated with colorectal cancer (CRC) incidence, but it is not clear if intake is associated with patient survival after diagnosis. METHODS: We pooled data from 7627 patients with stage I-IV CRC from 10 studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of intake of red and processed meat before diagnosis with overall and CRC-specific survival. RESULTS: Among 7627 patients with CRC, 2338 died, including 1576 from CRC, over a median follow-up time of 5.1 years. In multivariable-adjusted analyses, higher intake of red or processed meat was not associated with overall survival of patients with stage I-III CRC: Q4 vs Q1 red meat hazard ratio [HR], 1.08 (95% CI, 0.93-1.26) and Q4 vs Q1 processed meat HR, 1.10 (95% CI, 0.93-1.32) or with CRC-specific survival: Q4 vs Q1 red meat HR, 1.09 (95% CI, 0.89-1.33) and Q4 vs Q1 processed meat HR, 1.11 (95% CI, 0.87-1.42). Results were similar for patients with stage IV CRC. However, patients with stage I-III CRC who reported an intake of processed meat above the study-specific medians had a higher risk of death from any cause (HR, 1.12; 95% CI, 1.01-1.25) than patients who reported eating at or less than the median. CONCLUSION: In this large consortium of CRC patient cohorts, intake of red and processed meat before a diagnosis of CRC was not associated with shorter survival time after diagnosis, although a possible weak adverse association cannot be excluded. Studies that evaluate dietary data from several time points before and after cancer diagnosis are required to confirm these findings.
Title: Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach.
Authors: Di Credico G,  Edefonti V,  Polesel J,  Pauli F,  Torelli N,  Serraino D,  Negri E,  Luce D,  Stucker I,  Matsuo K,  Brennan P,  Vilensky M,  Fernandez L,  Curado MP,  Menezes A,  Daudt AW,  Koifman R,  Wunsch-Filho V,  Holcatova I,  Ahrens W,  Lagiou P,  Simonato L,  Richiardi L,  Healy C,  Kjaerheim K,  Conway DI,  Macfarlane TV,  Thomson P,  Agudo A,  Znaor A,  Boaventura Rios LF,  Toporcov TN,  Franceschi S,  Herrero R,  Muscat J,  Olshan AF,  Zevallos JP,  La Vecchia C,  Winn DM,  Sturgis EM,  Li G,  Fabianova E,  Lissowska J,  Mates D,  Rudnai P,  Shangina O,  Swiatkowska B,  Moysich K,  Zhang ZF,  Morgenstern H,  Levi F,  Smith E,  Lazarus P,  Bosetti C,  Garavello W,  Kelsey K,  McClean M,  Ramroth H,  Chen C,  Schwartz SM,  Vaughan TL,  Zheng T,  Menvielle G,  Boccia S,  Cadoni G,  Hayes RB,  Purdue M,  Gillison M,  Schantz S,  Yu GP,  Brenner H,  D'Souza G,  Gross ND,  Chuang SC,  Boffetta P,  Hashibe M,  Lee YA,  Dal Maso L
Journal: Oral Oncol
Date: 2019 Jul
Branches: OEEB
PubMed ID: 31178212
PMC ID: not available
Abstract: OBJECTIVES: This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures. MATERIALS AND METHODS: We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework. RESULTS: For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers. CONCLUSION: Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.
Title: Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium.
Authors: Fortner RT,  Poole EM,  Wentzensen NA,  Trabert B,  White E,  Arslan AA,  Patel AV,  Setiawan VW,  Visvanathan K,  Weiderpass E,  Adami HO,  Black A,  Bernstein L,  Brinton LA,  Buring J,  Clendenen TV,  Fournier A,  Fraser G,  Gapstur SM,  Gaudet MM,  Giles GG,  Gram IT,  Hartge P,  Hoffman-Bolton J,  Idahl A,  Kaaks R,  Kirsh VA,  Knutsen S,  Koh WP,  Lacey JV Jr,  Lee IM,  Lundin E,  Merritt MA,  Milne RL,  Onland-Moret NC,  Peters U,  Poynter JN,  Rinaldi S,  Robien K,  Rohan T,  Sánchez MJ,  Schairer C,  Schouten LJ,  Tjonneland A,  Townsend MK,  Travis RC,  Trichopoulou A,  van den Brandt PA,  Vineis P,  Wilkens L,  Wolk A,  Yang HP,  Zeleniuch-Jacquotte A,  Tworoger SS
Journal: Int J Cancer
Date: 2019 Jul 1
Branches: CGB, MEB, OD
PubMed ID: 30561796
PMC ID: PMC6488363
Abstract: Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
Title: Lifetime exposure to ultraviolet radiation and the risk of multiple sclerosis in the US radiologic technologists cohort study.
Authors: Gallagher LG,  Ilango S,  Wundes A,  Stobbe GA,  Turk KW,  Franklin GM,  Linet MS,  Freedman DM,  Alexander BH,  Checkoway H
Journal: Mult Scler
Date: 2019 Jul
Branches: REB
PubMed ID: 29932357
PMC ID: not available
Abstract: BACKGROUND: Low exposure to ultraviolet radiation (UVR) from sunlight may be a risk factor for developing multiple sclerosis (MS). Possible pathways may be related to effects on immune system function or vitamin D insufficiency, as UVR plays a role in the production of the active form of vitamin D in the body. OBJECTIVE: This study examined whether lower levels of residential UVR exposure from sunlight were associated with increased MS risk in a cohort of radiologic technologists. METHODS: Participants in the third and fourth surveys of the US Radiologic Technologists (USRT) Cohort Study eligible (N = 39,801) for analysis provided complete residential histories and reported MS diagnoses. MS-specialized neurologists conducted medical record reviews and confirmed 148 cases. Residential locations throughout life were matched to satellite data from NASA's Total Ozone Mapping Spectrometer (TOMS) project to estimate UVR dose. RESULTS: Findings indicate that MS risk increased as average lifetime levels of UVR exposures in winter decreased. The effects were consistent across age groups <40 years. There was little indication that low exposures during summer or at older ages were related to MS risk. CONCLUSION: Our findings are consistent with the hypothesis that UVR exposure reduces MS risk and may ultimately suggest prevention strategies.
Title: Neighbourhood disadvantage and depressive symptoms among adolescents followed into emerging adulthood.
Authors: Goldstein RB,  Lee AK,  Haynie DL,  Luk JW,  Fairman BJ,  Liu D,  Jeffers JS,  Simons-Morton BG,  Gilman SE
Journal: J Epidemiol Community Health
Date: 2019 Jul
Branches: BB
PubMed ID: 30928911
PMC ID: PMC6559828
Abstract: BACKGROUND: Residents of disadvantaged neighbourhoods report higher levels of depressive symptoms; however, few studies have employed prospective designs during adolescence, when depression tends to emerge. We examined associations of neighbourhood social fragmentation, income inequality and median household income with depressive symptoms in a nationally representative survey of adolescents. METHODS: The NEXT Generation Health Study enrolled 10th-grade students from 81 US high schools in the 2009-2010 school year. Depressive symptoms were assessed with the Modified Depression Scale (wave 1) and the paediatric Patient-Reported Outcome Measurement Information System (waves 2-6). Neighbourhood characteristics at waves 1, 3, 4, and 5 were measured at the census tract level using geolinked data from the American Community Survey 5-year estimates. We used linear mixed models to relate neighbourhood disadvantage to depressive symptoms controlling for neighbourhood and individual sociodemographic factors. RESULTS: None of the models demonstrated evidence for associations of social fragmentation, income inequality or median household income with depressive symptoms. CONCLUSION: Despite the prospective design, repeated measures and nationally representative sample, we detected no association between neighbourhood disadvantage and depressive symptoms. This association may not exist or may be too small to detect in a geographically dispersed sample. Given the public health significance of neighbourhood effects, future research should examine the developmental timing of neighbourhood effects across a wider range of ages than in the current sample, consider both objective and subjective measures of neighbourhood conditions, and use spatially informative techniques that account for conditions of nearby neighbourhoods.
Title: Maternal adipokines longitudinally measured across pregnancy and their associations with neonatal size, length, and adiposity.
Authors: Hinkle SN,  Rawal S,  Liu D,  Chen J,  Tsai MY,  Zhang C
Journal: Int J Obes (Lond)
Date: 2019 Jul
Branches: BB
PubMed ID: 30464233
PMC ID: PMC6529296
Abstract: BACKGROUND/OBJECTIVES: Maternal obesity impacts fetal growth as early as second trimester of pregnancy, yet little is known about the molecular mechanisms involved. We aimed to examine associations between maternal adipokines throughout pregnancy and neonatal size by prepregnancy obesity status. METHODS: In a prospective cohort of 2802 U.S. pregnant women from the NICHD Fetal Growth Studies-Singleton Cohort (2009-2013), biospecimens were analyzed in a matched case-control subset of 321 women. Blood was collected at 10-14, 15-26 (fasting), 23-31, and 33-39 gestational weeks. Plasma leptin and soluble leptin receptor (sOB-R) and total and high-molecular-weight (HMW)-adiponectin were measured. Free leptin was calculated as leptin/sOB-R. Birthweight was abstracted from medical records. Neonatal length and skinfolds were measured. RESULTS: Leptin and sOB-R in late pregnancy tended to be positively and negatively associated with neonatal length, respectively, while free leptin throughout pregnancy tended to be positively associated with length. Free leptin associations with neonatal length were differential by obesity (i.e., inversely among women without obesity and positively among women with obesity). A per unit increase in free leptin at 33-39 weeks was associated with a shorter neonatal length by -0.55 cm (95%CI, -0.83, -0.28) in women without obesity and longer length by 0.49 cm (95%CI, 0.34, 0.65) in women with obesity. HMW-adiponectin at 33-39 weeks was inversely associated with neonatal length (β = -1.29 cm; 95%CI, -1.74, -0.85) and skinfold thickness (β = -1.46 mm; 95%CI, -1.58, -0.56) among women with obesity. Free leptin across pregnancy tended to be negatively associated with neonatal skinfold thickness among women without obesity, while free leptin in early pregnancy was positively associated with skinfold thickness. CONCLUSIONS: Maternal adipokines were associated with multiple pathways that influence neonatal size including length and adiposity, which differed in timing across pregnancy and by prepregnancy obesity. These findings provide new potential insights into mechanisms and timing by which maternal obesity may impact fetal growth.
Title: Reproductive factors associated with breast cancer risk in Li-Fraumeni syndrome.
Authors: Khincha PP,  Best AF,  Fraumeni JF Jr,  Loud JT,  Savage SA,  Achatz MI
Journal: Eur J Cancer
Date: 2019 Jul
Branches: BB, CGB, OD
PubMed ID: 31212162
PMC ID: not available
Abstract: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant cancer predisposition syndrome with exceptionally high lifetime cancer risks, caused primarily by germline TP53 variants. Early-onset breast cancer is the most common cancer in women with LFS. Associations between female reproductive factors and breast cancer risk have been widely studied in the general population and BRCA1/2 mutation carriers but not in LFS. We evaluated whether reproductive factors are associated with breast cancer in LFS. Questionnaire data were collected for 152 women with confirmed germline TP53 variants enrolled in the National Cancer Institute's LFS study (NCT01443468); of which, 85 had breast cancer, confirmed by pathology/medical reports. Fisher's exact test and Cox proportional hazards were used to calculate the effect of reproductive factors on breast cancer risk. Lifetime breastfeeding for at least 7 months was associated with lower breast cancer risk (hazard ratio [HR] 0.57, p = 0.05). Parity did not independently change breast cancer risk (HR 1.08, p = 0.8) but suggested an increased risk with older age at first live birth (HR 2.14, p = 0.05). Age at menarche (HR 1.09, p = 0.24) and use of oral contraceptives (HR 0.88; p = 0.7) did not significantly affect breast cancer risk. In this first study of reproductive factors and breast cancer in women with LFS, breastfeeding was observed to be protective against breast cancer risk, especially with at least 7 months of lifetime breastfeeding. Older age at first live birth was suggested to slightly increase breast cancer risk. Larger prospective studies of reproductive factors are warranted in women with LFS before making definitive clinical recommendations.
Title: CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome.
Authors: Kulkarni S,  Lied A,  Kulkarni V,  Rucevic M,  Martin MP,  Walker-Sperling V,  Anderson SK,  Ewy R,  Singh S,  Nguyen H,  McLaren PJ,  Viard M,  Naranbhai V,  Zou C,  Lin Z,  Gatanaga H,  Oka S,  Takiguchi M,  Thio CL,  Margolick J,  Kirk GD,  Goedert JJ,  Hoots WK,  Deeks SG,  Haas DW,  Michael N,  Walker B,  Le Gall S,  Chowdhury FZ,  Yu XG,  Carrington M
Journal: Nat Immunol
Date: 2019 Jul
Branches: EBP
PubMed ID: 31209403
PMC ID: PMC6584055
Abstract: Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted in a corresponding change in CCR5 expression on CD4+ T cells. CCR5AS interfered with interactions between the RNA-binding protein Raly and the CCR5 3' untranslated region, protecting CCR5 messenger RNA from Raly-mediated degradation. Reduction in CCR5 expression through inhibition of CCR5AS diminished infection of CD4+ T cells with CCR5-tropic HIV in vitro. These data represent a rare determination of the functional importance of a genome-wide disease association where expression of a lncRNA affects HIV infection and disease progression.
Title: Age at Exposure to Radiation Determines Severity of Renal and Cardiac Disease in Rats.
Authors: Lenarczyk M,  Kronenberg A,  Mäder M,  North PE,  Komorowski R,  Cheng Q,  Little MP,  Chiang IH,  LaTessa C,  Jardine J,  Baker JE
Journal: Radiat Res
Date: 2019 Jul
Branches: REB
PubMed ID: 31095446
PMC ID: not available
Abstract: Radiotherapy with sparsely ionizing photons is a cornerstone of successful cancer treatment. Age at time of exposure to radiation is known to influence biological outcomes for many end points. The effect of dose and age at exposure upon the occurrence of radiogenic cardiovascular disease is poorly understood. The goal of this work was to determine the response of maleWAG/RijCmcr rats at 6 months of age to gamma rays, and at 6 months or 6 weeks of age to X rays, using clinically relevant biomarkers of cardiovascular disease and kidney injury. Overall, there were significant radiation-induced effects on the levels of bicarbonate (P=0.0016), creatinine (P=0.0002), calcium (P = 0.0009), triglycerides (P = 0.0269) and blood urea nitrogen, albumin, protein, AST, alkaline phosphatase, total cholesterol and HDL (all P < 0.0001). Of those variables with a significant radiation-dose effect, there were significant modifications by age at time of exposure for bicarbonate (P = 0.0033), creatinine (P = 0.0015), AST (P = 0.0040), total cholesterol (P = 0.0006) and blood urea nitrogen, calcium, albumin, protein, alkaline phosphatase and HDL (all P < 0.0001). Cardiac perivascular collagen content was significantly increased in rats that were 8.0 Gy X-ray irradiated at 6 weeks of age (P < 0.047) but not at 6 months of age. While systemic blood pressure was elevated in both cohorts after 8.0 Gy X-ray irradiation (compared to agematched sham-irradiated controls), the magnitude of the increase above baseline was greater in the younger rats (P < 0.05). These findings indicate that dose and age at time of irradiation determine the timeline and severity of cardiac and renal injury.
Title: Early-Onset Colorectal Cancer in Patients with Li Fraumeni Syndrome: Is It Really Enough to Justify Early Colon Cancer Screening?
Authors: Nirvana da Cruz Formiga M,  Ashton-Prolla P,  Alves de Souza Waddington Achatz MI
Journal: Gastroenterology
Date: 2019 Jul
Branches: CGB
PubMed ID: 30981786
PMC ID: not available
Abstract:
Title: A Prospective Study of the Association between Physical Activity and Risk of Prostate Cancer Defined by Clinical Features and TMPRSS2:ERG.
Authors: Pernar CH,  Ebot EM,  Pettersson A,  Graff RE,  Giunchi F,  Ahearn TU,  Gonzalez-Feliciano AG,  Markt SC,  Wilson KM,  Stopsack KH,  Gazeeva E,  Lis RT,  Parmigiani G,  Rimm EB,  Finn SP,  Giovannucci EL,  Fiorentino M,  Mucci LA
Journal: Eur Urol
Date: 2019 Jul
Branches: ITEB
PubMed ID: 30301696
PMC ID: PMC6451672
Abstract: BACKGROUND: Growing evidence shows that clinical and molecular subtypes of prostate cancer (PCa) have specific risk factors. Observational studies suggest that physical activity may lower the risk of aggressive PCa. To our knowledge, the association between physical activity and PCa defined by TMPRSS2:ERG has not been evaluated. OBJECTIVE: To prospectively examine the association between physical activity and risk of PCa defined by clinical features and TMPRSS2:ERG. DESIGN, SETTING, AND PARTICIPANTS: We studied 49160 men aged 40-75 yr in the Health Professionals Follow-up Study from 1986 to 2012. Data was collected at baseline and every 2 yr with >90% follow-up. Total and vigorous physical activity were measured in metabolic equivalent of task (MET)-h/wk. OUTCOME MEASURES AND STATISTICAL ANALYSIS: Advanced PCa was defined as stage T3b, T4, N1, or M1 at diagnosis and lethal PCa as distant metastases or death due to disease over follow-up. Presence of TMPRSS2:ERG was estimated by immunohistochemistry of ERG protein expression. Cox proportional hazards models were used to obtain multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence of subtype-specific PCa. RESULTS AND LIMITATIONS: During 26 yr of follow-up, 6411 developed PCa overall and 888 developed lethal disease. There were no significant associations between total physical activity and risk of PCa in the overall cohort. In multivariable-adjusted models, men in the highest quintile of vigorous activity had a significant 30% lower risk of advanced PCa (HR: 0.70, 95% CI: 0.53-0.92) and 25% lower risk of lethal PCa (HR: 0.75, 95% CI: 0.59-0.94) than men in the lowest quintile of vigorous activity. The association was independent of screening history. Vigorous activity was not associated with total PCa in the overall cohort but was inversely associated among highly screened men (top vs bottom quintile, HR: 0.83, 95% CI: 0.70-0.97). Of all cases, 945 were assayed for ERG (48% ERG-positive). Men with higher vigorous activity had a lower risk of ERG-positive PCa (top vs bottom quintile, HR: 0.71, 95% CI: 0.52-0.97). There was no significant association with the risk of ERG-negative disease (p heterogeneity=0.09). CONCLUSIONS: Our study confirms that vigorous physical activity is associated with lower risk of advanced and lethal PCa and provides novel evidence for a lower risk of TMPRSS2:ERG-positive disease. PATIENT SUMMARY: The identification of modifiable lifestyle factors for prevention of clinically important prostate cancer (PCa) is needed. In this report, we compared risk of PCa in men with different levels of physical activity. Men with higher vigorous activity had a lower risk of developing advanced and lethal PCa and PCa with the common TMPRSS2:ERG gene fusion.
Title: POT1 germline mutations but not TERT promoter mutations are implicated in melanoma susceptibility in a large cohort of Spanish melanoma families.
Authors: Potrony M,  Puig-Butille JA,  Ribera-Sola M,  Iyer V,  Robles-Espinoza CD,  Aguilera P,  Carrera C,  Malvehy J,  Badenas C,  Landi MT,  Adams DJ,  Puig S
Journal: Br J Dermatol
Date: 2019 Jul
Branches: ITEB
PubMed ID: 30451293
PMC ID: PMC6526091
Abstract: BACKGROUND: Germline mutations in telomere-related genes such as POT1 and TERT predispose individuals to familial melanoma. OBJECTIVES: To evaluate the prevalence of germline mutations in POT1 and TERT in a large cohort of Spanish melanoma-prone families (at least two affected first- or second-degree relatives). METHODS: Overall, 228 CDKN2A wild-type melanoma-prone families were included in the study. Screening of POT1 was performed in one affected person from each family and TERT was sequenced in one affected patient from 202 families (26 families were excluded owing to DNA exhaustion/degradation). TERT promoter sequencing was extended to an additional 30 families with CDKN2A mutation and 70 patients with sporadic multiple primary melanoma (MPM) with a family history of other cancers. RESULTS: We identified four families with potentially pathogenic POT1 germline mutations: a missense variant c.233T>C (p.Ile78Thr); a nonsense variant c.1030G>T (p.Glu344*); and two other variants, c.255G>A (r.125_255del) and c.1792G>A (r.1791_1792insAGTA, p.Asp598Serfs*22), which we confirmed disrupted POT1 mRNA splicing. A TERT promoter variant of unknown significance (c.-125C>A) was detected in a patient with MPM, but no germline mutations were detected in TERT promoter in cases of familial melanoma. CONCLUSIONS: Overall, 1·7% of our CDKN2A/CDK4-wild type Spanish melanoma-prone families carry probably damaging mutations in POT1. The frequency of TERT promoter germline mutations in families with melanoma in our population is extremely rare.
Title: Clinico-pathologic and mammographic characteristics of inflammatory and non-inflammatory breast cancer at six centers in North Africa.
Authors: Schairer C,  Hablas A,  Eldein IAS,  Gaafar R,  Rais H,  Mezlini A,  Ayed FB,  Ayoub WB,  Benider A,  Tahri A,  Khouchani M,  Aboulazm D,  Karkouri M,  Eissa S,  Pfeiffer RM,  Gadalla SM,  Swain SM,  Merajver SD,  Brown LM,  Soliman AS
Journal: Breast Cancer Res Treat
Date: 2019 Jul
Branches: BB, CGB, MEB
PubMed ID: 31006821
PMC ID: not available
Abstract: PURPOSE: We describe the clinico-pathologic and mammographic characteristics of inflammatory breast cancer (IBC) and non-IBC cases enrolled in a case-control study. Because IBC is a clinico-pathologic entity with rapid appearance of erythema and other signs, its diagnosis is based on clinical observation and thus, by necessity, subjective. Therefore, we evaluate our cases by photographic review by outside expert clinicians and by degree of adherence to the two most recent definitions of IBC: the international expert panel consensus statement and American Joint Committee on Cancer (AJCC) 8th edition (we used the slightly less restrictive 7th edition definition for our study). METHODS: We enrolled 267 IBC and 274 age- and geographically matched non-IBC cases at 6 sites in Egypt, Tunisia, and Morocco in a case-control study of IBC conducted between 2009 and 2015. We collected clinico-pathologic and mammographic data and standardized medical photographs of the breast. RESULTS: We identified many differences between IBC and non-IBC cases: 54.5% versus 68.8% were estrogen receptor-positive, 39.9% versus 14.8% human epidermal growth factor receptor 2-positive, 91% versus 4% exhibited erythema, 63% versus 97% had a mass, and 57% versus 10% had mammographic evidence of skin thickening. Seventy-six percent of IBC cases adhered to the expert panel consensus statement and 36% to the AJCC definition; 86 percent were confirmed as IBC by either photographic review or adherence to the consensus statement. CONCLUSIONS: We successfully identified distinct groups of IBC and non-IBC cases. The reliability of IBC diagnosis would benefit from expert review of standardized medical photographs and associated clinical information.
Title: Longitudinal investigation of haematological alterations among permethrin-exposed pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture study.
Authors: Shearer JJ,  Beane Freeman LE,  Liu D,  Andreotti G,  Hamilton J,  Happel J,  Lynch CF,  Alavanja MC,  Hofmann JN
Journal: Occup Environ Med
Date: 2019 Jul
Branches: BB, OEEB
PubMed ID: 30962255
PMC ID: not available
Abstract: OBJECTIVES: Permethrin use has been associated with an increased risk of multiple myeloma (MM) among pesticide applicators. However, the biological plausibility and mechanisms underlying this association are not fully understood. The aim of this study was to assess whether exposure to permethrin is related to haematological alterations among occupationally exposed pesticide applicators. METHODS: We conducted a longitudinal study among 33 pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture study comparing haematological parameters in the offseason with the day after permethrin exposure and, for 27 participants, approximately 3 weeks postexposure. Complete blood counts with white blood cell differential and lymphocyte subsets were measured at each visit. Multivariate linear mixed effects models were used to assess the relationship between natural log-transformed haematological parameters and exposure to permethrin. RESULTS: The adjusted geometric mean immature granulocyte count was elevated among pesticide applicators following permethrin exposure compared with their offseason levels (37% increase, 95% CI 6% to 76%). Modest but statistically significant (p<0.05) alterations in red blood cell (RBC) parameters (eg, decreased RBC count and haemoglobin and increased mean corpuscular volume and RBC distribution width-SD) were also observed the day after permethrin use compared with offseason levels; decreases in RBC count and haemoglobin and increases in RBC distribution width-SD persisted approximately 3 weeks after permethrin use. CONCLUSIONS: Altered haematological parameters could be indicative of disrupted haematopoiesis, providing insights into the biological plausibility of the observed association between permethrin use and MM risk among pesticide applicators.
Title: APOBEC-mediated Mutagenesis as a Likely Cause of FGFR3 S249C Mutation Over-representation in Bladder Cancer.
Authors: Shi MJ,  Meng XY,  Lamy P,  Banday AR,  Yang J,  Moreno-Vega A,  Chen CL,  Dyrskjøt L,  Bernard-Pierrot I,  Prokunina-Olsson L,  Radvanyi F
Journal: Eur Urol
Date: 2019 Jul
Branches: LTG
PubMed ID: 30975452
PMC ID: not available
Abstract: FGFR3 is one of the most frequently mutated genes in bladder cancer and a driver of an oncogenic dependency. Here we report that only the most common recurrent FGFR3 mutation, S249C (TCC→TGC), represents an APOBEC-type motif and is probably caused by the APOBEC-mediated mutagenic process, accounting for its over-representation. We observed significant enrichment of the APOBEC mutational signature and overexpression of AID/APOBEC gene family members in bladder tumors with S249C compared to tumors with other recurrent FGFR3 mutations. Analysis of replication fork directionality suggests that the coding strand of FGFR3 is predominantly replicated as a lagging strand template that could favor the formation of hairpin structures, facilitating mutagenic activity of APOBEC enzymes. In vitro APOBEC deamination assays confirmed S249 as an APOBEC target. We also found that the FGFR3 S249C mutation was common in three other cancer types with an APOBEC mutational signature, but rare in urothelial tumors without APOBEC mutagenesis and in two diseases probably related to aging. PATIENT SUMMARY: We propose that APOBEC-mediated mutagenesis can generate clinically relevant driver mutations even within suboptimal motifs, such as in the case of FGFR3 S249C, one of the most common mutations in bladder cancer. Knowledge about the etiology of this mutation will improve our understanding of the molecular mechanisms of bladder cancer.
Title: Incidence of testicular tumor subtypes according to the updated WHO classification, North Rhine-Westphalia, Germany, 2008-2013.
Authors: Stang A,  Rusner C,  Trabert B,  Oosterhuis JW,  McGlynn KA,  Heidinger O
Journal: Andrology
Date: 2019 Jul
Branches: MEB
PubMed ID: 30578617
PMC ID: not available
Abstract: BACKGROUND: In 2016, the WHO introduced an updated classification for testicular tumors. The application of this updated classification to cancer registry data requires some recoding of tumors. OBJECTIVES: The aim of this study was to provide up-to-date population-based incidence estimates of subtypes of testicular germ cell tumors (TGCT) according to the updated classification. MATERIAL AND METHODS: We reviewed 2251 pathology reports (42.9%) out of 5252 testicular tumors at the cancer registry of North Rhine-Westphalia for the years 2008-2013. We used population counts to estimate age-standardized incidence rates per million person-years (EUROSTAT revised European Standard Population). RESULTS: The application of the updated WHO classification resulted in a recoding of 8.9% of all testicular tumors. While the recodings have no influence on the incidence of seminomatous and non-seminomatous TGCTs that include mixed TGCTs, they influence the incidence of individual histological types of seminomatous and non-seminomatous TGCTs. Among the 4935 testicular germ cell tumors (TGCT), 23.7% were mixed TGCTs. Overall, 46.9% of all mixed TGCTs included seminoma and age-standardized incidence rates were highest for the combination seminoma plus embryonal carcinoma (5.9 per million person-years) and embryonal carcinoma plus teratoma (4.9 per million person-years). The median age at diagnosis was higher for mixed TGCTs including seminoma (31 years) than those that did not include seminoma (28 years). DISCUSSION AND CONCLUSIONS: Population-based incidence time trends for seminomatous and non-seminomatous TGCTs that include mixed TGCTs are not distorted by the introduction of the WHO update. Trend distortions can only be expected if time trends of individual histological subtypes of the seminomatous and non-seminomatous TGCTs are examined.
Title: The relationship between terminal duct lobular unit features and mammographic density among Chinese breast cancer patients.
Authors: Sung H,  Guo C,  Li E,  Li J,  Pfeiffer RM,  Guida JL,  Cora R,  Hu N,  Deng J,  Figueroa JD,  Sherman ME,  Gierach GL,  Lu N,  Yang XR
Journal: Int J Cancer
Date: 2019 Jul 1
Branches: BB, ITEB, MEB
PubMed ID: 30561789
PMC ID: PMC6488407
Abstract: Extensive mammographic density (MD), a well-established breast cancer risk factor, is a radiological representation of stromal and epithelial breast tissue content. In studies conducted predominantly among Caucasian women, histologic measures of reduced terminal duct lobular unit (TDLU) involution have been correlated with extensive MD, but independently associated with breast cancer risk. We therefore examined associations between TDLU measures and MD among Chinese women, a low-risk population but with high prevalence of dense breasts. Diagnostic pre-treatment digital mammograms were obtained from 144 breast cancer cases at a tertiary hospital in Beijing and scored using the Breast Imaging Reporting and Data System (BI-RADS) density classification. TDLU features were assessed using three standardized measures (count/100 mm2 , span [μm], and acini count/TDLU) in benign tissues. Associations between each of TDLU measures and MD were examined using generalized linear models for TDLU count and span and polytomous logistic regression for acini count with adjustment for potential confounders stratified by age. Among women ≥50 years, 63% had dense breasts; cases with dense breasts (BI-RADS, c-d) had greater TDLU count (21.1 [SE = 2.70] vs. 9.0 [SE = 1.83]; p = 0.0004), longer span (480.6 μm [SE = 24.6] vs. 393.8 μm [SE = 31.8]; p = 0.03), and greater acini count (ORtrend = 16.1; 95%CI = 4.08-63.1; ptrend < 0.0001) compared to those with non-dense breasts (BI-RADS, a-b). Among women <50 years, 91% had dense breasts, precluding our ability to detect associations. Our findings are consistent with previously reported associations between extensive MD and reduced TDLU involution, supporting the hypothesis that breast cancer risk associated with extensive MD may be related to the amount of "at-risk" epithelium.
Title: Parental longevity and survival among patients with multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study.
Authors: Sverrisdóttir IS,  Lund SH,  Turesson I,  Björkholm M,  Goldin LR,  Landgren O,  Kristinsson SY
Journal: Br J Haematol
Date: 2019 Jul
Branches: ITEB
PubMed ID: 30906990
PMC ID: PMC6589120
Abstract: Parental longevity is associated with an increased life expectancy; results with regard to specific diseases are conflicting. There are limited data focusing on host characteristics and their effect on survival among multiple myeloma (MM) patients and individuals with monoclonal gammopathy of undetermined significance (MGUS). Therefore, our aim was to evaluate the impact of parental longevity on survival of patients with MM and MGUS. A total of 4675 patients with MM, 6812 MGUS patients and 13 398 population-based controls for MM as well as 19 110 controls for MGUS, from 1988 to 2013, were included in the study. Longevity was defined as >90 years of age. Among MM patients, parental longevity was associated with a decreased risk of death [hazard ratio (HR) = 0·92, 95% confidence interval (CI) 0·84-0·99] and the same was true for MGUS patients (HR = 0·87, 95% CI 0·78-0·96). Having one long lived parent significantly decreased the risk of death in both groups, but was not statistically significant when both parents exceeded 90 years of age. In conclusion, parental longevity decreases the risk of death for patients with MM and MGUS which may reflect the importance of the host's genetic and environmental factors in relation to survival.
Title: Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk: A Transcriptome-Wide Association Study in Over 140,000 European Descendants.
Authors: Wu L,  Wang J,  Cai Q,  Cavazos TB,  Emami NC,  Long J,  Shu XO,  Lu Y,  Guo X,  Bauer JA,  Pasaniuc B,  Penney KL,  Freedman ML,  Kote-Jarai Z,  Witte JS,  Haiman CA,  Eeles RA,  Zheng W,  and the PRACTICAL, CRUK, BPC3, CAPS, PEGASUS Consortia
Journal: Cancer Res
Date: 2019 Jul 1
Branches: EBP, OD, OEEB, MEB
PubMed ID: 31101764
PMC ID: PMC6606384
Abstract: Genome-wide association study-identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many of these identified associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at P < 2.61 × 10-6, a Bonferroni-corrected threshold, including nine genes that remained significant at P < 2.61 × 10-6 after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology. SIGNIFICANCE: This study identifies novel prostate cancer genetic loci and possible causal genes, advancing our understanding of the molecular mechanisms that drive prostate cancer.
Title: Inflammatory Potential of Diet, Inflammation-Related Lifestyle Factors, and Risk of Pancreatic Cancer: Results from the NIH-AARP Diet and Health Study.
Authors: Zheng J,  Wirth MD,  Merchant AT,  Zhang J,  Shivappa N,  Stolzenberg-Solomon RZ,  Hebert JR,  Steck SE
Journal: Cancer Epidemiol Biomarkers Prev
Date: 2019 Jul
Branches: MEB
PubMed ID: 31040136
PMC ID: PMC6606345
Abstract: BACKGROUND: Chronic inflammation is implicated in pancreatic cancer, and can be modulated by diet and other lifestyle factors. We examined the association between Dietary Inflammatory Index (DII) scores and pancreatic cancer risk in the NIH-AARP Diet and Health Study, and examined effect modification by inflammation-related lifestyle factors, including body mass index, cigarette smoking, diabetes, alcohol drinking, and use of non-steroidal anti-inflammatory drugs. METHODS: Energy-adjusted DII scores (E-DII) were computed on the basis of food frequency questionnaire responses for foods and dietary supplements. Cox proportional hazards models were fitted and effect modification was examined by adding a cross-product of each effect modifier with E-DII quintile in the multivariable-adjusted model. RESULTS: There were 2,824 primary incident pancreatic cancers diagnosed during a median of 13.4 years follow-up, and there was no association between E-DII scores and pancreatic cancer risk among either men [HRQ5vsQ1, 1.00; 95% confidence interval (CI), 0.86-1.16] or women (HRQ5vsQ1, 1.00; 95% CI, 0.82-1.21) in the multivariable-adjusted model, and no association was detected by any cancer stage. The E-DII and pancreatic cancer association was not modified by any of the inflammation-related lifestyle factors examined. CONCLUSIONS: Results from this large prospective study did not support an association between inflammatory potential of diet and pancreatic cancer, or effect modification by other inflammation-related lifestyle factors. IMPACT: Inflammatory potential of diet may not be related to pancreatic cancer risk. Future cohort studies with more frequent dietary measures could be useful in determining the appropriate timing of dietary intake in relation to pancreatic cancer etiology.
Title: Associations between mammographic density and tumor characteristics in Chinese women with breast cancer.
Authors: Li E,  Guida JL,  Tian Y,  Sung H,  Koka H,  Li M,  Chan A,  Zhang H,  Tang E,  Guo C,  Deng J,  Hu N,  Lu N,  Gierach GL,  Li J,  Yang XR
Journal: Breast Cancer Res Treat
Date: 2019 Jun 28
Branches: BB, ITEB, MEB
PubMed ID: 31254158
PMC ID: not available
Abstract: PURPOSE: Mammographic density (MD) is a strong risk factor for breast cancer, yet its relationship with tumor characteristics is not well established, particularly in Asian populations. METHODS: MD was assessed from a total of 2001 Chinese breast cancer patients using Breast Imaging Reporting and Data System (BI-RADS) categories. Molecular subtypes were defined using immunohistochemical status on ER, PR, HER2, and Ki-67, as well as tumor grade. Multinomial logistic regression was used to test associations between MD and molecular subtype (luminal A = reference) adjusting for age, body mass index (BMI), menopausal status, parity, and nodal status. RESULTS: The mean age at diagnosis was 51.7 years (SD = 10.7) and the average BMI was 24.7 kg/m2 (SD = 3.8). The distribution of BI-RADS categories was 7.4% A = almost entirely fat, 24.2% B = scattered fibroglandular dense, 49.4% C = heterogeneously dense, and 19.0% D = extremely dense. Compared to women with BI-RADS = A/B, women with BI-RADS = D were more likely to have HER2-enriched tumors (OR = 1.81, 95% CI 1.08-3.06, p = 0.03), regardless of menopausal status. The association was only observed in women with normal (< 25 kg/m2) BMI (OR = 2.43, 95% CI 1.24-4.76, p < 0.01), but not among overweight/obese women (OR: 0.98, 95% CI 0.38-2.52, p = 0.96). CONCLUSIONS: Among Chinese women with normal BMI, higher breast density was associated with HER2-enriched tumors. The results may partially explain the higher proportion of HER2+ tumors previously reported in Asian women.
Title: Sex specific associations in genome wide association analysis of renal cell carcinoma.
Authors: Laskar RS,  Muller DC,  Li P,  Machiela MJ,  Ye Y,  Gaborieau V,  Foll M,  Hofmann JN,  Colli L,  Sampson JN,  Wang Z,  Bacq-Daian D,  Boland A,  Abedi-Ardekani B,  Durand G,  Le Calvez-Kelm F,  Robinot N,  Blanche H,  Prokhortchouk E,  Skryabin KG,  Burdett L,  Yeager M,  Radojevic-Skodric S,  Savic S,  Foretova L,  Holcatova I,  Janout V,  Mates D,  Rascu S,  Mukeria A,  Zaridze D,  Bencko V,  Cybulski C,  Fabianova E,  Jinga V,  Lissowska J,  Lubinski J,  Navratilova M,  Rudnai P,  Świątkowska B,  Benhamou S,  Cancel-Tassin G,  Cussenot O,  Trichopoulou A,  Riboli E,  Overvad K,  Panico S,  Ljungberg B,  Sitaram RT,  Giles GG,  Milne RL,  Severi G,  Bruinsma F,  Fletcher T,  Koppova K,  Larsson SC,  Wolk A,  Banks RE,  Selby PJ,  Easton DF,  Pharoah P,  Andreotti G,  Beane Freeman LE,  Koutros S,  Albanes D,  Männistö S,  Weinstein S,  Clark PE,  Edwards TL,  Lipworth L,  Carol H,  Freedman ML,  Pomerantz MM,  Cho E,  Kraft P,  Preston MA,  Wilson KM,  Michael Gaziano J,  Sesso HD,  Black A,  Freedman ND,  Huang WY,  Anema JG,  Kahnoski RJ,  Lane BR,  Noyes SL,  Petillo D,  Teh BT,  Peters U,  White E,  Anderson GL,  Johnson L,  Luo J,  Chow WH,  Moore LE,  Choueiri TK,  Wood C,  Johansson M,  McKay JD,  Brown KM,  Rothman N,  Lathrop MG,  Deleuze JF,  Wu X,  Brennan P,  Chanock SJ,  Purdue MP,  Scelo G
Journal: Eur J Hum Genet
Date: 2019 Jun 23
Branches: BB, CGR, ITEB, LGS, LTG, MEB, OD, OEEB
PubMed ID: 31231134
PMC ID: not available
Abstract: Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.
Title: Mortality Risks of Dual- and Poly-Tobacco Product Users in the United States.
Authors: Choi K,  Inoue-Choi M,  McNeel TS,  Freedman ND
Journal: Am J Epidemiol
Date: 2019 Jun 21
Branches: MEB
PubMed ID: 31225859
PMC ID: not available
Abstract: Increasing numbers of adults in the United States use more than one tobacco product. Most use cigarettes in combination with other tobacco products. However, little is known about the all-cause and cancer-specific mortality risks of dual- and poly-tobacco use. We examined these associations by pooling nationally-representative data from the 1991, 1992, 1998, 2000, 2005, and 2010 National Health Interview Surveys (n=118,144). Mortality information was obtained by linkage to the National Death Index. Cigarette smokers who additionally used other tobacco products smoked as many if not more cigarettes per day than exclusive cigarette smokers. Furthermore, cigarette smokers who additionally used other tobacco products had mortality risks that were as high and sometimes higher than exclusive cigarette smokers. As tobacco use patterns continue to change and diversify, future studies need to carefully assess the impact of non-cigarette tobacco products on cigarette use and determine disease risks.
Title: Relationship Between Serum Alpha-Tocopherol and Overall and Cause-Specific Mortality.
Authors: Huang J,  Weinstein SJ,  Yu K,  Männistö S,  Albanes D
Journal: Circ Res
Date: 2019 Jun 21
Branches: BB, MEB
PubMed ID: 31219752
PMC ID: not available
Abstract: RATIONALE: Although there has been a long-standing interest in the human health effects of vitamin E, a comprehensive analysis of the association between circulating vitamin E and long-term mortality has not been conducted. OBJECTIVE: Determine whether serum α-tocopherol (the predominant form of vitamin E) is related to long-term overall and cause-specific mortality and elucidate the dose-response relationships with better quantification of the associations. METHODS AND RESULTS: We conducted a biochemical analysis of 29 092 participants in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention) that originally tested vitamin E and β-carotene supplementation. Serum α-tocopherol was measured at baseline using high-performance liquid chromatography, and during a 30-year follow-up we identified 23 787 deaths, including deaths from cardiovascular disease (9867), cancer (7687), respiratory disease (2161), diabetes mellitus (119), injuries and accidents (1255), and other causes (2698). After adjusting for major risk factors, we found that men with higher serum α-tocopherol had significantly lower all-cause mortality (hazard ratios=0.83, 0.79, 0.75, and 0.78 for quintile 2 (Q2)-Q5 versus Q1, respectively; Ptrend<0.0001), and significantly decreased mortality from cardiovascular disease, heart disease, stroke, cancer, respiratory disease, and other causes, with risk reductions from 17% to 47% for the highest versus lowest quintile. The α-tocopherol association with overall mortality was similar across subgroups of smoking intensity, years of smoking, alcohol consumption, trial supplementation, and duration of follow-up. The association was, however, significantly modified by baseline age and body mass index, with stronger inverse associations for younger men and men with a lower body mass index ( Pinteraction≤0.006). CONCLUSIONS: In this long-term prospective cohort study, higher baseline serum α-tocopherol biochemical status was associated with lower risk of overall mortality and mortality from all major causes. Our data support the long-term health benefits of higher serum α-tocopherol for overall and chronic disease mortality and should be replicated in other more diverse populations.
Title: Integration of Metabolomic and Other Omics Data in Population-Based Study Designs: An Epidemiological Perspective.
Authors: Chu SH,  Huang M,  Kelly RS,  Benedetti E,  Siddiqui JK,  Zeleznik OA,  Pereira A,  Herrington D,  Wheelock CE,  Krumsiek J,  McGeachie M,  Moore SC,  Kraft P,  Mathé E,  Lasky-Su J,  Consortium of Metabolomics Studies Statistics Working Group
Journal: Metabolites
Date: 2019 Jun 18
Branches: MEB
PubMed ID: 31216675
PMC ID: not available
Abstract: It is not controversial that study design considerations and challenges must be addressed when investigating the linkage between single omic measurements and human phenotypes. It follows that such considerations are just as critical, if not more so, in the context of multi-omic studies. In this review, we discuss (1) epidemiologic principles of study design, including selection of biospecimen source(s) and the implications of the timing of sample collection, in the context of a multi-omic investigation, and (2) the strengths and limitations of various techniques of data integration across multi-omic data types that may arise in population-based studies utilizing metabolomic data.
Title: Citrus fruit intake and gastric cancer: The stomach cancer pooling (StoP) project consortium.
Authors: Bertuccio P,  Alicandro G,  Rota M,  Pelucchi C,  Bonzi R,  Galeone C,  Bravi F,  Johnson KC,  Hu J,  Palli D,  Ferraroni M,  López-Carrillo L,  Lunet N,  Ferro A,  Malekzadeh R,  Zaridze D,  Maximovitch D,  Vioque J,  Navarrete-Munoz EM,  Pakseresht M,  Hernández-Ramírez RU,  López-Cervantes M,  Ward M,  Pourfarzi F,  Tsugane S,  Hidaka A,  Zhang ZF,  Kurtz RC,  Lagiou P,  Lagiou A,  Boffetta P,  Boccia S,  Negri E,  La Vecchia C
Journal: Int J Cancer
Date: 2019 Jun 15
Branches: OEEB
PubMed ID: 30521095
PMC ID: not available
Abstract: Diets rich in vegetables and fruit have been associated with reduced risk of gastric cancer, and there is suggestive evidence that citrus fruits have a protective role. Our study aimed at evaluating and quantifying the association between citrus fruit intake and gastric cancer risk. We conducted a one-stage pooled analysis including 6,340 cases and 14,490 controls from 15 case-control studies from the stomach cancer pooling (StoP) project consortium. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) of gastric cancer across study-specific tertiles of citrus fruit intake (grams/week) were estimated by generalized linear mixed effect models, with logistic link function and random intercept for each study. The models were adjusted for sex, age, and the main recognized risk factors for gastric cancer. Compared to the first third of the distribution, the adjusted pooled OR (95% CI) for the highest third was 0.80 (0.73-0.87). The favourable effect of citrus fruits increased progressively until three servings/week and leveled off thereafter. The magnitude of the association was similar between cancer sub-sites and histotypes. The analysis by geographic area showed no association in studies from the Americas. Our data confirm an inverse association between citrus fruits and gastric cancer and provide precise estimates of the magnitude of the association. However, the null association found in studies from America and in some previous cohort studies prevent to draw definite conclusions on a protective effect of citrus fruit consumption.
Title: Lung cancer risk by geologic coal deposits: A case-control study of female never-smokers from Xuanwei and Fuyuan, China.
Authors: Wong JYY,  Downward GS,  Hu W,  Portengen L,  Seow WJ,  Silverman DT,  Bassig BA,  Zhang J,  Xu J,  Ji BT,  Li J,  He J,  Yang K,  Tian L,  Shen M,  Huang Y,  Vermeulen R,  Rothman N,  Lan Q
Journal: Int J Cancer
Date: 2019 Jun 15
Branches: OEEB
PubMed ID: 30511435
PMC ID: not available
Abstract: Coal types vary around the world because of geochemical differences in their source deposits; however, the influence of coal emissions from different deposits on human health remains unexplored. To address this issue, we conducted the first study of the relationship between coal use from various deposits and lung cancer risk in Xuanwei and Fuyuan, counties in China where lung cancer rates are among the highest in the world among female never-smokers due to use of bituminous ("smoky") coal for heating and cooking. We conducted a population-based case-control study of 1031 lung cancer cases and 493 controls among never-smoking women in Xuanwei and Fuyuan. Logistic regression models were used to estimate associations between coal use from various deposits across the lifecourse and lung cancer risk. There was substantial heterogeneity in risks by coal deposit (p = 7.8E-05). Compared to non-smoky coal users, risks by smoky coal deposit ranged from OR = 7.49 (95% CI: 3.43-16.38) to OR = 33.40 (95% CI: 13.07-85.34). Further, women born into homes that used smoky coal and subsequently changed to non-smoky coal had a higher risk (OR = 10.83 (95% CI: 4.61-25.46)) than women born into homes that used non-smoky coal and changed to smoky coal (OR = 4.74 (95% CI: 2.03-11.04, pdifference = 0.04)). Our study demonstrates that various sources of coal have considerably different impact on lung cancer in this population and suggests that early-life exposure to carcinogenic emissions may exert substantial influence on health risks later in life. These factors should be considered when evaluating the health risks posed by exposure to coal combustion emissions.
Title: Genome-wide Burden of Rare Short Deletions Is Enriched in Major Depressive Disorder in Four Cohorts.
Authors: Zhang X,  Abdellaoui A,  Rucker J,  de Jong S,  Potash JB,  Weissman MM,  Shi J,  Knowles JA,  Pato C,  Pato M,  Sobell J,  Smit JH,  Hottenga JJ,  de Geus EJC,  Lewis CM,  Buttenschøn HN,  Craddock N,  Jones I,  Jones L,  McGuffin P,  Mors O,  Owen MJ,  Preisig M,  Rietschel M,  Rice JP,  Rivera M,  Uher R,  Gejman PV,  Sanders AR,  Boomsma D,  Penninx BWJH,  Breen G,  Levinson DF
Journal: Biol Psychiatry
Date: 2019 Jun 15
Branches: BB
PubMed ID: 31003785
PMC ID: not available
Abstract: BACKGROUND: Major depressive disorder (MDD) is moderately heritable, with a high prevalence and a presumed high heterogeneity. Copy number variants (CNVs) could contribute to the heritable component of risk, but the two previous genome-wide association studies of rare CNVs did not report significant findings. METHODS: In this meta-analysis of four cohorts (5780 patients and 6626 control subjects), we analyzed the association of MDD to 1) genome-wide burden of rare deletions and duplications, partitioned by length (<100 kb or >100 kb) and other characteristics, and 2) individual rare exonic CNVs and CNV regions. RESULTS: Patients with MDD carried significantly more short deletions than control subjects (p = .0059) but not long deletions or short or long duplications. The confidence interval for long deletions overlapped with that for short deletions, but long deletions were 70% less frequent genome-wide, reducing the power to detect increased burden. The increased burden of short deletions was primarily in intergenic regions. Short deletions in cases were also modestly enriched for high-confidence enhancer regions. No individual CNV achieved thresholds for suggestive or significant association after genome-wide correction. p values < .01 were observed for 15q11.2 duplications (TUBGCP5, CYFIP1, NIPA1, and NIPA2), deletions in or near PRKN or MSR1, and exonic duplications of ATG5. CONCLUSIONS: The increased burden of short deletions in patients with MDD suggests that rare CNVs increase the risk of MDD by disrupting regulatory regions. Results for longer deletions were less clear, but no large effects were observed for long multigenic CNVs (as seen in schizophrenia and autism). Further studies with larger sample sizes are warranted.
Title: Trends in mortality due to cancer in the US by age and county-level income, 1999-2015.
Authors: Withrow DR,  de González AB,  Spillane S,  Freedman ND,  Best AF,  Chen Y,  Shiels MS
Journal: J Natl Cancer Inst
Date: 2019 Jun 14
Branches: BB, IIB, MEB, REB
PubMed ID: 31199459
PMC ID: not available
Abstract: Disparities in cancer mortality by county-level income have increased. It is unclear whether these widening disparities have affected older and younger adults equally. National death certificate data were utilized to ascertain cancer deaths during 1999-2015. Average annual percent changes (AAPCs) in mortality rates and mortality rate ratios (RRs) were estimated by county-level income quintile and age (25-64 vs. ≥65). Among 25-64-year-olds, cancer mortality rates were 30% higher (RR = 1.30, 95% confidence interval [CI]:1.29-1.31) in the lowest vs. highest income counties in 1999-2001, and 56% higher (RR = 1.56;95%CI:1.55-1.57) in 2013-2015; the disparities among ≥65-year-olds were smaller but also widened over time (RR1999-2001:1.04,95%CI:1.03-1.05; RR2013-2015:1.14,95%CI:1.13-1.14). Widening disparities occurred across cancer sites. If all counties had the mortality rates of the highest income counties, 21.5% of cancer deaths among 25-64-year-olds and 7.3% of cancer deaths in ≥ 65-year-olds would have been avoided in 2015. These results highlight an ongoing need for equity-focused interventions, particularly among younger adults.
Title: Weekday and weekend sleep duration and mortality among middle-to-older aged White and Black adults in a low-income southern US cohort.
Authors: Xiao Q,  Blot WJ,  Matthews CE
Journal: Sleep Health
Date: 2019 Jun 13
Branches: MEB
PubMed ID: 31204307
PMC ID: not available
Abstract: INTRODUCTION: Both short and long sleep have been associated with higher mortality. However, most studies are conducted in predominantly White or Asian populations and little is known about the sleep-mortality relationship in Blacks. Given the high prevalence of short and long sleep in Blacks, it is important to examine the health effects of sleep in this population. METHODS: We studied sleep duration in relation to all-cause, cardiovascular and cancer mortality in 55,375 participants age 40-79 at enrollment in the Southern Community Cohort Study, of whom ~2/3 are Black. Weekday and weekend sleep durations were self-reported. Mortality follow up started at baseline (2002-2009) and was regularly updated until 2015 via linkage to Social Security Administration and the National Death Index. We used Cox proportional hazards model adjusting for multiple covariates to estimate relative risks associated with sleep duration. RESULTS: We found U-shaped relationships between weekday and weekend sleep duration and all-cause mortality, with the effects stronger in Whites than Blacks. Risks for all-cause mortality were significantly elevated by about 25% among Whites and about 10% among Blacks reporting either less than 5 hours or more than 9 hours of sleep compared with those reporting 8 hours of sleep. The associations among Whites but not Blacks were even stronger for cardiovascular disease mortality, whereas no association between sleep duration and cancer mortality was found in either group. CONCLUSIONS: Our results suggest that short and long sleep durations may be weaker predictors of total and cardiovascular mortality in Blacks than in Whites.