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Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study.
- Author(s): 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 GEM;
- 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 BM;
- 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 EJ;
- 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;
- GEMO Study Collaborators;
- HEBON;
- EMBRACE;
- 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
- et al.
Published Web Location
https://watermark.silverchair.com/djy132.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAkkwggJFBgkqhkiG9w0BBwagggI2MIICMgIBADCCAisGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM-63BK7qD5jEw2dHVAgEQgIIB_GliPrCq4Qiy9RSHJ5bYSdkPVDLG35c6sKaZyLzUSlXjjVe5dNj7T4QoqzA5DFcBEavB_AAFApW3KeZB-KjJUS1RWSDWVkHrDtCf8A39GjV8L9_4R8xXjt9xE9m5iZK_iwiXG8JQHQYaNz3MjB3h6rfxaw0ndarvwSgWo2udgTgwd-oIAoz6knbT6eHVvI4HW-wh3d0XSctFPIdtyJLOL2r67hY_NiQE9kkjWzF69DgdTlgPm6crNJasXY12ZlDZr99Cwi8u_kgyOEjpbuVanhmEA0CqZMiD2kkWXNo data is associated with this publication.
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/m2 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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.