Q Guo, S Burgess, C Turman, MK Bolla, Q Wang, M Lush, J Abraham, K Aittomäki, IL Andrulis, C Apicella, V Arndt, M Barrdahl, J Benitez, CD Berg, C Blomqvist, SE Bojesen, B Bonanni, JS Brand, H Brenner, A Broeks, B Burwinkel, C Caldas, D Campa, F Canzian, J Chang-Claude, SJ Chanock, S-F Chin, FJ Couch, A Cox, SS Cross, C Cybulski, K Czene, H Darabi, P Devilee, WR Diver, AM Dunning, HM Earl, DM Eccles, AB Ekici, M Eriksson, DG Evans, PA Fasching, J Figueroa, D Flesch-Janys, H Flyger, SM Gapstur, MM Gaudet, GG Giles, G Glendon, M Grip, J Gronwald, L Haeberle, CA Haiman, P Hall, U Hamann, S Hankinson, JM Hartikainen, A Hein, L Hiller, FB Hogervorst, B Holleczek, MJ Hooning, RN Hoover, K Humphreys, DJ Hunter, A Hüsing, A Jakubowska, A Jukkola-Vuorinen, R Kaaks, M Kabisch, V Kataja, kConFab/AOCS Investigators, JA Knight, LB Koppert, V-M Kosma, VN Kristensen, D Lambrechts, L Le Marchand, J Li, A Lindblom, S Lindström, J Lissowska, J Lubinski, MJ Machiela, A Mannermaa, S Manoukian, S Margolin, F Marme, JWM Martens, C McLean, P Menéndez, RL Milne, A Marie Mulligan, TA Muranen, H Nevanlinna, P Neven, SF Nielsen, BG Nordestgaard, JE Olson, JIA Perez, P Peterlongo, K-A Phillips, CJ Poole, K Pylkäs, P Radice, N Rahman, T Rüdiger, A Rudolph, EJ Sawyer, F Schumacher, P Seibold, C Seynaeve, M Shah, A Smeets, MC Southey, RAEM Tollenaar, I Tomlinson, H Tsimiklis, H-U Ulmer, C Vachon, AMW van den Ouweland, LJ Van't Veer, H Wildiers, W Willett, R Winqvist, MP Zamora, G Chenevix-Trench, T Dörk, DF Easton, M García-Closas, P Kraft, JL Hopper, W Zheng, MK Schmidt, PDP Pharoah
Int J Epidemiol
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.