Association Of TGFB1 And TGFBR2 Polymorphisms With Breast Cancer Risk

Objective To investigate the association of TGFB1 C-509T, T+29C and TGFBR2 G-875A with risk of breast cancer, and clarify whether the three polymorphisms influence the risk of breast cancer with different expression status of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2).Methods TGFB1 C-509T, T+29C and TGFBR2 G-875A polymorphisms were genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP) in fresh surgically tissues (n=82) and archived paraffin-embedded specimens (n=88) from 170 patients with breast cancer, and peripheral blood samples from 178 cancer-free females. Evaluation of ER, PR and HER2 expression was performed using immunohistochemical staining. Logistic regression analysis was done to determine risk of breast cancer, which presented with odds ratios (ORs) and their 95% confidence intervals (95% CIs).Results No difference in TGFB1 C-509T, T+29C genotype and allele frequencies between patients and controls was observed; However, the frequency of TGFBR2 -875A allele was higher in cancer-free females than breast cancer patients (24.2% vs. 17.9%, P = 0.05). Interestingly, when stratifying by expression of ER, PR and HER2, we found that TGFBR2 -875A allele correlated significantly to decreased risk of breast cancer with ER positive (OR = 0.57, 95% CI = 0.35-0.92), PR positive (OR = 0.54, 95% CI = 0.34-0.88), both ER and PR are positive (OR = 0.55, 95% CI = 0.33-0.92) and HER2 negative (OR = 0.55, 95% CI = 0.34-0.88) under dominant genetic model.Conclusion This is the first study to suggest that TGFBR2 -875A allele may decrease the risk of breast cancer and TGFBR2 -875A allele is associated with a significantly decreased risk of hormone-dependent breast cancer and HER2-negative breast cancer in Chinese female population.