title: Testing for Gene-Environment Interactions Using a Prospective Family Cohort Design: Body Mass Index in Early and Later Adulthood and Risk of Breast Cancer.
abstract: 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.
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Dite
authors.forename: Robert J
authors.initials: RJ
authors.lastname: MacInnis
authors.forename: Adrian
authors.initials: A
authors.lastname: Bickerstaffe
authors.forename: James G
authors.initials: JG
authors.lastname: Dowty
authors.forename: Roger L
authors.initials: RL
authors.lastname: Milne
authors.forename: Antonis C
authors.initials: AC
authors.lastname: Antoniou
authors.forename: Prue
authors.initials: P
authors.lastname: Weideman
authors.forename: Carmel
authors.initials: C
authors.lastname: Apicella
authors.forename: Graham G
authors.initials: GG
authors.lastname: Giles
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Southey
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Phillips
authors.forename: Aung Ko
authors.initials: AK
authors.lastname: Win
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
mesh_terms: D000293:Adolescent; D000328:Adult; D001315:Australia / Q000453:epidemiology; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005192:Family Health / Q000706:statistics & numerical data*; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009520:New Zealand / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017584:Reproductive History; D018570:Risk Assessment / Q000379:methods; D055815:Young Adult
keywords: BOADICEA; body mass index; breast cancer; cohort studies; familial risk; family studies; gene-environment interaction