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Title: Body mass index and breast cancer survival: a Mendelian randomization analysis.
Authors: Guo Q,  Burgess S,  Turman C,  Bolla MK,  Wang Q,  Lush M,  Abraham J,  Aittomäki K,  Andrulis IL,  Apicella C,  Arndt V,  Barrdahl M,  Benitez J,  Berg CD,  Blomqvist C,  Bojesen SE,  Bonanni B,  Brand JS,  Brenner H,  Broeks A,  Burwinkel B,  Caldas C,  Campa D,  Canzian F,  Chang-Claude J,  Chanock SJ,  Chin SF,  Couch FJ,  Cox A,  Cross SS,  Cybulski C,  Czene K,  Darabi H,  Devilee P,  Diver WR,  Dunning AM,  Earl HM,  Eccles DM,  Ekici AB,  Eriksson M,  Evans DG,  Fasching PA,  Figueroa J,  Flesch-Janys D,  Flyger H,  Gapstur SM,  Gaudet MM,  Giles GG,  Glendon G,  Grip M,  Gronwald J,  Haeberle L,  Haiman CA,  Hall P,  Hamann U,  Hankinson S,  Hartikainen JM,  Hein A,  Hiller L,  Hogervorst FB,  Holleczek B,  Hooning MJ,  Hoover RN,  Humphreys K,  Hunter DJ,  Hüsing A,  Jakubowska A,  Jukkola-Vuorinen A,  Kaaks R,  Kabisch M,  Kataja V,  kConFab/AOCS Investigators,  Knight JA,  Koppert LB,  Kosma VM,  Kristensen VN,  Lambrechts D,  Le Marchand L,  Li J,  Lindblom A,  Lindström S,  Lissowska J,  Lubinski J,  Machiela MJ,  Mannermaa A,  Manoukian S,  Margolin S,  Marme F,  Martens JWM,  McLean C,  Menéndez P,  Milne RL,  Marie Mulligan A,  Muranen TA,  Nevanlinna H,  Neven P,  Nielsen SF,  Nordestgaard BG,  Olson JE,  Perez JIA,  Peterlongo P,  Phillips KA,  Poole CJ,  Pylkäs K,  Radice P,  Rahman N,  Rüdiger T,  Rudolph A,  Sawyer EJ,  Schumacher F,  Seibold P,  Seynaeve C,  Shah M,  Smeets A,  Southey MC,  Tollenaar RAEM,  Tomlinson I,  Tsimiklis H,  Ulmer HU,  Vachon C,  van den Ouweland AMW,  Van't Veer LJ,  Wildiers H,  Willett W,  Winqvist R,  Zamora MP,  Chenevix-Trench G,  Dörk T,  Easton DF,  García-Closas M,  Kraft P,  Hopper JL,  Zheng W,  Schmidt MK,  Pharoah PDP
Journal: Int J Epidemiol
Date: 2017 Dec 1
Branches: EBP, ITEB, LGS, MEB, OD, OEEB
PubMed ID: 29232439
PMC ID: not available
Abstract: Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95). Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.