Body mass index and breast cancer survival: a Mendelian randomization analysis. (9th October 2017)

• Record Type: Journal Article
• Authors: Guo, Qi; Burgess, Stephen; Turman, Constance; Bolla, Manjeet K; Wang, Qin; Lush, Michael; Abraham, Jean; Aittomäki, Kristiina; Andrulis, Irene L; Apicella, Carmel; Arndt, Volker; Barrdahl, Myrto; Benitez, Javier; Berg, Christine D; Blomqvist, Carl; Bojesen, Stig E; Bonanni, Bernardo; Brand, Judith S; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Caldas, Carlos; Campa, Daniele; Canzian, Federico; Chang-Claude, Jenny; Chanock, Stephen J; Chin, Suet-Feung; Couch, Fergus J; Cox, Angela; Cross, Simon S; Cybulski, Cezary; Czene, Kamila; Darabi, Hatef; Devilee, Peter; Diver, W Ryan; Dunning, Alison M; Earl, Helena M; Eccles, Diana M; Ekici, Arif B; Eriksson, Mikael; Evans, D Gareth; Fasching, Peter A; Figueroa, Jonine; Flesch-Janys, Dieter; Flyger, Henrik; Gapstur, Susan M; Gaudet, Mia M; Giles, Graham G; Glendon, Gord; Grip, Mervi; Gronwald, Jacek; Haeberle, Lothar; Haiman, Christopher A; Hall, Per; Hamann, Ute; Hankinson, Susan; Hartikainen, Jaana M; Hein, Alexander; Hiller, Louise; Hogervorst, Frans B; Holleczek, Bernd; Hooning, Maartje J; Hoover, Robert N; Humphreys, Keith; Hunter, David J; Hüsing, Anika; Jakubowska, Anna; Jukkola-Vuorinen, Arja; Kaaks, Rudolf; Kabisch, Maria; Kataja, Vesa; Knight, Julia A; Koppert, Linetta B; Kosma, Veli-Matti; Kristensen, Vessela N; Lambrechts, Diether; Le Marchand, Loic; Li, Jingmei; Lindblom, Annika; Lindström, Sara; Lissowska, Jolanta; Lubinski, Jan; Machiela, Mitchell J; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Marme, Federik; Martens, John WM; McLean, Catriona; Menéndez, Primitiva; Milne, Roger L; Marie Mulligan, Anna; Muranen, Taru A; Nevanlinna, Heli; Neven, Patrick; Nielsen, Sune F; Nordestgaard, Børge G; Olson, Janet E; Perez, Jose IA; Peterlongo, Paolo; Phillips, Kelly-Anne; Poole, Christopher J; Pylkäs, Katri; Radice, Paolo; Rahman, Nazneen; Rüdiger, Thomas; Rudolph, Anja; Sawyer, Elinor J; Schumacher, Fredrick; Seibold, Petra; Seynaeve, Caroline; Shah, Mitul; Smeets, Ann; Southey, Melissa C; Tollenaar, Rob A E M; Tomlinson, Ian; Tsimiklis, Helen; Ulmer, Hans-Ulrich; Vachon, Celine; van den Ouweland, Ans MW; Van't Veer, Laura J; Wildiers, Hans; Willett, Walter; Winqvist, Robert; Zamora, M Pilar; Chenevix-Trench, Georgia; Dörk, Thilo; Easton, Douglas F; García-Closas, Montserrat; Kraft, Peter; Hopper, John L; Zheng, Wei; Schmidt, Marjanka K; Pharoah, Paul DP;
• Is Part Of: International journal of epidemiology. Volume 46:Number 6(2017)
• Page Start: 1814
• Page End: 1822
• Publication Date: 2017-10-09
• Subjects: Body mass index -- breast cancer survival -- Mendelian randomization -- epidemiology -- genetics; Epidemiology -- Periodicals; 614.4
• DOI: 10.1093/ije/dyx131
• Languages: English
• ISSNs: 0300-5771

Abstract

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.