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_kgyOEjpbuVanhmEA0CqZMiD2kkWXAbstract
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.
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