TY - JOUR
T1 - Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers
T2 - A Mendelian Randomization Study
AU - GEMO Study Collaborators
AU - HEBON
AU - EMBRACE
AU - Qian, Frank
AU - Wang, Shengfeng
AU - Mitchell, Jonathan
AU - McGuffog, Lesley
AU - Barrowdale, Daniel
AU - Leslie, Goska
AU - Oosterwijk, Jan C.
AU - Chung, Wendy K.
AU - Evans, D. Gareth
AU - Engel, Christoph
AU - Kast, Karin
AU - Aalfs, Cora M.
AU - Adank, Muriel A.
AU - Adlard, Julian
AU - Agnarsson, Bjarni A.
AU - Aittomäki, Kristiina
AU - Alducci, Elisa
AU - Andrulis, Irene L.
AU - Arun, Banu K.
AU - Ausems, Margreet G.E.M.
AU - Azzollini, Jacopo
AU - Barouk-Simonet, Emmanuelle
AU - Barwell, Julian
AU - Belotti, Muriel
AU - Benitez, Javier
AU - Berger, Andreas
AU - Borg, Ake
AU - Bradbury, Angela R.
AU - Brunet, Joan
AU - Buys, Saundra S.
AU - Caldes, Trinidad
AU - Caligo, Maria A.
AU - Campbell, Ian
AU - Caputo, Sandrine M.
AU - Chiquette, Jocelyne
AU - Claes, Kathleen B.M.
AU - Margriet Collée, J.
AU - Couch, Fergus J.
AU - Coupier, Isabelle
AU - Daly, Mary B.
AU - Davidson, Rosemarie
AU - Diez, Orland
AU - Domchek, Susan M.
AU - Donaldson, Alan
AU - Dorfling, Cecilia M.
AU - Eeles, Ros
AU - Feliubadaló, Lidia
AU - Foretova, Lenka
AU - Fowler, Jeffrey
AU - Antoniou, Antonis C.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85064286333&partnerID=8YFLogxK
U2 - 10.1093/jnci/djy132
DO - 10.1093/jnci/djy132
M3 - Article (Academic Journal)
C2 - 30312457
AN - SCOPUS:85064286333
SN - 0027-8874
VL - 111
SP - 350
EP - 364
JO - JNCI Journal of the National Cancer Institute
JF - JNCI Journal of the National Cancer Institute
IS - 4
ER -