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- Title
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; Aittomäki, Kristiina; Alducci, Elisa; Andrulis, Irene L; Arun, Banu K; Ausems, Margreet G E M
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>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.
- Subjects
STATURE; BODY mass index; BREAST cancer; BRCA genes; GENETIC carriers; BREAST cancer risk factors
- Publication
JNCI: Journal of the National Cancer Institute, 2019, Vol 111, Issue 4, p350
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djy132