Testing for Gene-Environment Interactions Using a Prospective Family Cohort Design: Body Mass Index in Early and Later Adulthood and Risk of Breast Cancer
A partir de données de 3 études de cohortes australiennes incluant 9 126 participants issus de 3 222 familles et 288 patientes atteintes d'un cancer du sein, cette étude prospective évalue l'association entre une histoire familiale de cancer du sein, l'indice de masse corporelle mesuré à différents moments de la vie et le risque de développer la maladie
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 significant, 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.