Familial clustering of obesity and breast cancer

One of the most striking characteristics of breast cancer (BC) is a tendency to familial aggregation. In order to evaluate whether familial clustering of obesity could account, at least in part, for the familial aggregation of BC, we compared the adult body size of entire sets of first-degree relatives belonging to 60 families with two or more cases of BC (case families) and 120 BC-free families (control families). Case families included an index case recently admitted for primary BC who had a confirmed first-degree family history for the disease. Control families included one population-based healthy index control with no family history and age-matched (2:1) to index cases. Index cases and controls, recruited from a pool of participants in a large case-control study, completed a questionnaire covering their own body size history as well as that of each of their first-degree relatives (598 case and 1,128 control relatives) using a validated system of body silhouette drawings. The odds ratio (OR) for premenopausal familial BC associated with having one parent markedly obese compared to none was 0.17 (95% confidence interval [CI] 0.04-0.65), while having both parents obese resulted in an OR of 0.25 (95% CI 0.04-1.56). Obesity among siblings was not related to premenopausal familial BC risk nor was familial obesity a significant predictor of familial BC after menopause. Index cases from both menopausal groups tended to be thinner than their unaffected relatives at age 40 years and thereafter. The inverse relationship between parental obesity and premenopausal BC risk is concordant with the protective effect of obesity on early-onset BC previously reported at the individual level.