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Pracoviště: Division of Evolution and Genomic Sciences Geno...

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

Qian, Frank
Autor Qian, Frank Department of Medicine, The University of Chicago, Chicago, IL
Wang, Shengfeng
Autor Wang, Shengfeng Center for Clinical Cancer Genetics, The University of Chicago, Chicago, IL. Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
Mitchell, Jonathan
Autor Mitchell, Jonathan Division of Gastroenterology, Department of Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA
McGuffog, Lesley
Autor McGuffog, Lesley Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
Barrowdale, Daniel
Autor Barrowdale, Daniel Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
Leslie, Goska
Autor Leslie, Goska Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
Oosterwijk, Jan C
Autor Oosterwijk, Jan C Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Chung, Wendy K
Autor Chung, Wendy K Departments of Pediatrics and Medicine, Columbia University, New York, NY
Evans, D Gareth
Autor Evans, D Gareth Division of Evolution and Genomic Sciences, Genomic Medicine, Manchester Academic Health Sciences Centre, University of Manchester, Central Manchester University Hospitals, NHS Foundation Trust, Manchester, UK
Engel, Christoph
Autor Engel, Christoph Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany. LIFE - Leipzig Research Centre for Civilization Diseases, University of Leipzig, Leipzig, Germany

Journal of the National Cancer Institute. 2019 ; 111 (4) : 350-364. [pub] 20190401

J Natl Cancer Inst
ISSN 1460-2105
Medvik
Zdroj

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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