Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study
- 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.; Aittomaki, 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.; Collee, J. Margriet; Couch, Fergus J.; Coupier, Isabelle; Daly, Mary B.; Davidson, Rosemarie; Diez, Orland; Domchek, Susan M.; Donaldson, Alan; Dorfling, Cecilia M.; Eeles, Ros; Feliubadalo, Lidia; Foretova, Lenka; Fowler, Jeffrey; Friedman, Eitan; Frost, Debra; Ganz, Patricia A.; Garber, Judy; Garcia-Barberan, Vanesa; Glendon, Gord; Godwin, Andrew K.; Gomez 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, Angel; Jakubowska, Anna; Kaczmarek, Katarzyna; Kang, Eunyoung; Karlan, Beth Y.; Kets, Carolien M.; Kim, Sung-Won; Kim, Zisun; Kwong, Ava; Laitman, Yael; Lasset, Christine; Lee, Min Hyuk; Lee, Jong Won; 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.; Selkirk, Christina G. Hutten; Shah, Payal D.; Simard, Jacques; Singer, Christian F.; Sokolowska, Johanna; Stoppa-Lyonnet, Dominique; Sutter, Christian; Tan, Yen Yen; Teixeira, Manuel R.; 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
- Issue Date
- Apr-2019
- Publisher
- Oxford University Press
- Keywords
- breast cancer; BRCA1/2 mutation carriers
- Citation
- Journal of the National Cancer Institute, v.111, no.4, pp 350 - 364
- Pages
- 15
- Journal Title
- Journal of the National Cancer Institute
- Volume
- 111
- Number
- 4
- Start Page
- 350
- End Page
- 364
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/4591
- DOI
- 10.1093/jnci/djy132
- ISSN
- 0027-8874
1460-2105
- 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/m2 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.
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Collections - College of Medicine > Department of General Surgery > 1. Journal Articles
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