Body mass, polymorphisms in obesity-related genes, and the risk of developing breast cancer among women with benign breast disease

Background: A cohort study was conducted among post-menopausal women to determine whether genetic polymorphisms in selected obesity-related genes (PPARG, LPL, LEPR, PON1, PON2, TNF-α) were associated with the progression of benign breast disease (BBD) to breast cancer and whether the selected polymorphisms modified the association between body mass and breast cancer among women with BBD. Methods: Among participants in an ongoing cohort study, 994 Caucasian post-menopausal women had a breast biopsy for BBD. Of these women, 61 subsequently developed breast cancer. A short questionnaire was administered at baseline in 1989. Genotypes were determined using DNA extracted from blood collected in 1989. Results: In this cohort, body mass index (BMI) was positively associated with the risk of developing breast cancer. In contrast, polymorphisms in PON1 (Gln192Arg) and LEPR (IVS2 + 6920) were associated with a decreased risk of developing invasive breast cancer. No statistically significant associations were observed for polymorphisms in PPARG, PON2, LPL, or TNF and breast cancer risk or for interactions between the polymorphisms and BMI and breast cancer risk. Conclusions: The findings suggest that specific polymorphisms in the PON1 and LEPR genes may play a role in progression of BBD to breast cancer among post-menopausal Caucasian women.