An investigation of the biological basis of an interaction of abdominal fat distribution and family history of breast cancer. A nested study of sisters in the Iowa Women's Health Study (United States)

Objective: The present study examined whether levels of testosterone, sex hormone binding globulin (SHBG), or insulin levels might underlie an increased risk of postmenopausal breast cancer in women with both high waist-tohip ratio and a family history of breast cancer disease that was noted earlier in the Iowa Women's Health Study. Methods: Participants for the current study were selected from 1922 sister groups (3978 women) in the Iowa Women's Health Study cohort. Two groups were included: (1) those with no family history of breast cancer and at least one sister with a high waist-to-hip ratio; or (2) those with a positive family history of breast cancer and at least one sister with a high waist-to-hip ratio. Testosterone, SHBG and insulin were measured by radioimmunoassay from 245 fasting blood samples. Results: Familial correlations among members of 66 families were estimated at 0.32, 0.28 and 0.25 for serum insulin, free testosterone and SHBG; respectively. Fasting serum insulin was significantly higher in breast cancer family history negative women than in family history positive women, in direct opposition to our a priori hypothesis. No significant differences were observed in serum SHBG or free testosterone across family history categories. Conclusion: This study corroborates a genetic component to fasting serum insulin, free testosterone and SHBG levels. It seems unlikely that insulin, SHBG, or testosterone explain the interaction between waist-to-hip ratio and family history of breast cancer among participants in the Iowa Women's Health Study.