Relations of insulin resistance and serum concentrations of estradiol and sex hormone-binding globulin to potential breast cancer risk factors

There is a hypothesis that hyperinsulinemia or insulin resistance may be a mediator for breast cancer risk factors. On the other hand, some. but not a ll, of the well-known risk factors of breast cancer have been associated wi th serum estrogen concentrations. We assessed the relationships of potentia l breast cancer risk factors to indicators of insulin resistance, fasting p lasma insulin concentration and homeostasis model assessment insulin resist ance (BOMA-R), in 88 postmenopausal Japanese women. We also examined whethe r insulin resistance would explain the association of breast cancer risk fa ctors with serum estradiol and sex hormone-binding globulin (SHBG). Informa tion on potential breast cancer risk factors, such as demographic character istics, smoking and drinking habits, diet, exercise, menstrual and reproduc tive factors, was obtained by self-administered health questionnaire includ ing a validated semiquantitative food frequency questionnaire. Body mass in dex (BMI) was significantly correlated with the ratio of estradiol to SHBG (Spearman r=0.30, P=0.0004), fasting plasma insulin (r=0.45) and HOMA-R (r= 0.43, P=0.0001) after controlling for age. The correlations were still sign ificant between BMI and estradiol/SWBG ratio (r=0.21, P=0.047) after contro lling for fasting plasma insulin and between BMI and fasting plasma insulin (r=0.40, P=0.0001) as well as HOMA-R (r=0.38, P=0.0003) after controlling for estradiol/SHBG; ratio. There is a possibility that effect of BMI on bre ast cancer risk is mediated by both insulin resistance and estrogen metabol ism.