Testing for Gene-Environment Interactions Using a Prospective Family Cohort Design: Body Mass Index in Early and Later Adulthood and Risk of Breast Cancer
American Journal of Epidemiology
Oxford University Press
MetadataShow full item record
Dite, G., MacInnis, R., Bickerstaffe, A., Dowty, J., Milne, R., Antoniou, A., Weideman, P., et al. (2017). Testing for Gene-Environment Interactions Using a Prospective Family Cohort Design: Body Mass Index in Early and Later Adulthood and Risk of Breast Cancer. American Journal of Epidemiology, 185 (6), 487-500. https://doi.org/10.1093/aje/kww241
The ability to classify people according to their underlying genetic susceptibility to a disease is increasing with new knowledge, better family data, and more sophisticated risk prediction models, allowing for more effective prevention and screening. To do so, however, we need to know whether risk associations are the same for people with different genetic susceptibilities. To illustrate one way to estimate such gene-environment interactions, we used prospective data from 3 Australian family cancer cohort studies, 2 enriched for familial risk of breast cancer. There were 288 incident breast cancers in 9,126 participants from 3,222 families. We used Cox proportional hazards models to investigate whether associations of breast cancer with body mass index (BMI; weight (kg)/height (m)$^2$ ) at age 18–21 years, BMI at baseline, and change in BMI differed according to genetic risk based on lifetime breast cancer risk from birth, as estimated by BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) software, adjusted for age at baseline data collection. Although no interactions were statistically signifi- cant, we have demonstrated the power with which gene-environment interactions can be investigated using a cohort enriched for persons with increased genetic risk and a continuous measure of genetic risk based on family history.
BOADICEA, body mass index, breast cancer, cohort studies, familial risk, family studies, gene-environment interaction
The Australian Breast Cancer Family Registry (ABCFR) was supported in Australia by the National Health and Medical Research Council, the New South Wales Cancer Council, the Victorian Health Promotion Foundation, the Victorian Breast Cancer Research Consortium, Cancer Australia, and the National Breast Cancer Foundation. The ABCFR was also supported by the National Cancer Institute, US National Institutes of Health, under Request for Application CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry: the University of Melbourne (Melbourne, Victoria, Australia) (grant U01 CA69638); the Fox Chase Cancer Center (Philadelphia, Pennsylvania) (grant U01 CA69631); the Huntsman Cancer Institute (Salt Lake City, Utah) (grant U01 CA69446); Columbia University (New York, New York) (grant U01 CA69398); the Cancer Prevention Institute of California (Fremont, California) (grant U01 CA69417); and Cancer Care Ontario (Toronto, Ontario, Canada) (grant U01 CA69467). The Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab) was supported by a grant from the Australian National Breast Cancer Foundation and previously by the National Health and Medical Research Council, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. The Australasian Colorectal Cancer Family Registry (ACCFR) was supported by grant UM1 CA167551 from the National Cancer Institute, US National Institutes of Health, and through cooperative agreements with the members and Principal Investigators of the ACCFR (grants U01 CA074778 and U01/U24 CA097735). A.K.W. is a National Health and Medical Research Council Early Career Fellow. M.A.J. is a National Health and Medical Research Council Senior Research Fellow. K.A.P. is an Australian National Breast Cancer Foundation Fellow.
External DOI: https://doi.org/10.1093/aje/kww241
This record's URL: https://www.repository.cam.ac.uk/handle/1810/263190