Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study. (12th October 2018)

• Record Type: Journal Article
• Authors: Qian, Frank; Wang, Shengfeng; Mitchell, Jonathan; McGuffog, Lesley; Barrowdale, Daniel; Leslie, Goska; Oosterwijk, Jan C; Chung, Wendy K; Evans, D Gareth; Engel, Christoph; Kast, Karin; Aalfs, Cora M; Adank, Muriel A; Adlard, Julian; Agnarsson, Bjarni A; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L; Arun, Banu K; Ausems, Margreet G E M; Azzollini, Jacopo; Barouk-Simonet, Emmanuelle; Barwell, Julian; Belotti, Muriel; Benitez, Javier; Berger, Andreas; Borg, Ake; Bradbury, Angela R; Brunet, Joan; Buys, Saundra S; Caldes, Trinidad; Caligo, Maria A; Campbell, Ian; Caputo, Sandrine M; Chiquette, Jocelyne; Claes, Kathleen B M; Margriet Collée, J; Couch, Fergus J; Coupier, Isabelle; Daly, Mary B; Davidson, Rosemarie; Diez, Orland; Domchek, Susan M; Donaldson, Alan; Dorfling, Cecilia M; Eeles, Ros; Feliubadaló, Lidia; Foretova, Lenka; Fowler, Jeffrey; Friedman, Eitan; Frost, Debra; Ganz, Patricia A; Garber, Judy; Garcia-Barberan, Vanesa; Glendon, Gord; Godwin, Andrew K; Gómez Garcia, Encarna B; Gronwald, Jacek; Hahnen, Eric; Hamann, Ute; Henderson, Alex; Hendricks, Carolyn B; Hopper, John L; Hulick, Peter J; Imyanitov, Evgeny N; Isaacs, Claudine; Izatt, Louise; Izquierdo, Ángel; Jakubowska, Anna; Kaczmarek, Katarzyna; Kang, Eunyoung; Karlan, Beth Y; Kets, Carolien M; Kim, Sung-Won; Kim, Zisun; Kwong, Ava; Laitman, Yael; Lasset, Christine; Hyuk Lee, Min; Won Lee, Jong; Lee, Jihyoun; Lester, Jenny; Lesueur, Fabienne; Loud, Jennifer T; Lubinski, Jan; Mebirouk, Noura; Meijers-Heijboer, Hanne E J; Meindl, Alfons; Miller, Austin; Montagna, Marco; Mooij, Thea M; Morrison, Patrick J; Mouret-Fourme, Emmanuelle; Nathanson, Katherine L; Neuhausen, Susan L; Nevanlinna, Heli; Niederacher, Dieter; Nielsen, Finn C; Nussbaum, Robert L; Offit, Kenneth; Olah, Edith; Ong, Kai-Ren; Ottini, Laura; Park, Sue K; Peterlongo, Paolo; Pfeiler, Georg; Phelan, Catherine M; Poppe, Bruce; Pradhan, Nisha; Radice, Paolo; Ramus, Susan J; Rantala, Johanna; Robson, Mark; Rodriguez, Gustavo C; Schmutzler, Rita K; Hutten Selkirk, Christina G; Shah, Payal D; Simard, Jacques; Singer, Christian F; Sokolowska, Johanna; Stoppa-Lyonnet, Dominique; Sutter, Christian; Yen Tan, Yen; Teixeira, R Manuel; Teo, Soo H; Terry, Mary Beth; Thomassen, Mads; Tischkowitz, Marc; Toland, Amanda E; Tucker, Katherine M; Tung, Nadine; van Asperen, Christi J; van Engelen, Klaartje; van Rensburg, Elizabeth J; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Weitzel, Jeffrey N; Yannoukakos, Drakoulis; Greene, Mark H; Rookus, Matti A; Easton, Douglas F; Chenevix-Trench, Georgia; Antoniou, Antonis C; Goldgar, David E; Olopade, Olufunmilayo I; Rebbeck, Timothy R; Huo, Dezheng;
• Is Part Of: Journal of the National Cancer Institute. Volume 111:Number 4(2019)
• Page Start: 350
• Page End: 364
• Publication Date: 2018-10-12
• Subjects: Cancer -- Periodicals; Cancer -- Research -- Periodicals; 616.994
• DOI: 10.1093/jnci/djy132
• Languages: English
• ISSNs: 0027-8874

Abstract

Abstract: Background: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. Methods: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. Results: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m 2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m 2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. Conclusion: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.