Publications

Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study.

Author(s): Qian F,  Wang S,  Mitchell J,  McGuffog L,  Barrowdale D,  Leslie G,  Oosterwijk JC,  Chung WK,  Evans DG,  Engel C,  Kast K,  Aalfs CM,  Adank MA,  Adlard J,  Agnarsson BA,  Aittomäki K,  Alducci E,  Andrulis IL,  Arun BK,  Ausems MGEM,  Azzollini J,  Barouk-Simonet E,  Barwell J,  Belotti M,  Benitez J,  Berger A,  Borg A,  Bradbury AR,  Brunet J,  Buys SS,  Caldes T,  Caligo MA,  Campbell I,  Caputo SM,  Chiquette J,  Claes KBM,  Margriet Collée J,  Couch FJ,  Coupier I,  Daly MB,  Davidson R,  Diez O,  Domchek SM,  Donaldson A,  Dorfling CM,  Eeles R,  Feliubadaló L,  Foretova L,  Fowler J,  Friedman E,  Frost D,  Ganz PA,  Garber J,  Garcia-Barberan V,  Glendon G,  Godwin AK,  Gómez Garcia EB,  Gronwald J,  Hahnen E,  Hamann U,  Henderson A,  Hendricks CB,  Hopper JL,  Hulick PJ,  Imyanitov EN,  Isaacs C,  Izatt L,  Izquierdo Á,  Jakubowska A,  Kaczmarek K,  Kang E,  Karlan BY,  Kets CM,  Kim SW,  Kim Z,  Kwong A,  Laitman Y,  Lasset C,  Hyuk Lee M,  Won Lee J,  Lee J,  Lester J,  Lesueur F,  Loud JT,  Lubinski J,  Mebirouk N,  Meijers-Heijboer HEJ,  Meindl A,  Miller A,  Montagna M,  Mooij TM,  Morrison PJ,  Mouret-Fourme E,  Nathanson KL,  Neuhausen SL,  Nevanlinna H,  Niederacher D,  Nielsen FC,  Nussbaum RL,  Offit K,  Olah E,  Ong KR,  Ottini L,  Park SK,  Peterlongo P,  Pfeiler G,  Phelan CM,  Poppe B,  Pradhan N,  Radice P,  Ramus SJ,  Rantala J,  Robson M,  Rodriguez GC,  Schmutzler RK,  Hutten Selkirk CG,  Shah PD,  Simard J,  Singer CF,  Sokolowska J,  Stoppa-Lyonnet D,  Sutter C,  Yen Tan Y,  Teixeira RM,  Teo SH,  Terry MB,  Thomassen M,  Tischkowitz M,  Toland AE,  Tucker KM,  Tung N,  van Asperen CJ,  van Engelen K,  van Rensburg EJ,  Wang-Gohrke S,  Wappenschmidt B,  Weitzel JN,  Yannoukakos D,  GEMO Study Collaborators,  HEBON,  EMBRACE,  Greene MH,  Rookus MA,  Easton DF,  Chenevix-Trench G,  Antoniou AC,  Goldgar DE,  Olopade OI,  Rebbeck TR,  Huo D

Journal: J Natl Cancer Inst

Date: 2019 Apr 1

Major Program(s) or Research Group(s): NCORP

PubMed ID: 30312457

PMC ID: PMC6449171

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.