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A functional polymorphism of TGFBR2 is associated with risk of breast cancer with ER(+), PR(+), ER(+)PR(+) and HER2(-) expression in women.

Little is known about the correlation between TGFBR2 G-875A and breast cancer risk. Moreover, the associations of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) in breast cancer tissues with the TGFB1 C-509T, T+29C and TGFBR2 G-875A polymorphisms remain to be determined. In this study, we genotyped for TGFB1 C-509T, T+29C and TGFBR2 G-875A in fresh surgically resected tissues (n=82) and archived paraffin-embedded specimens (n=88) from 170 patients with breast cancer, as well as peripheral blood samples from 178 cancer-free female individuals. Evaluation of ER, PR and HER2 expression was performed using immunohistochemical staining. Logistic regression analysis was carried out to determine the risk of breast cancer by calculating the odds ratios (ORs) and their 95% confidence intervals (CIs). As a result, no difference was observed in the TGFB1 C-509T, T+29C genotype and allele frequencies between patients and controls. However, the frequency of the TGFBR2 -875A allele was marginally higher in cancer-free female individuals than that of women with breast cancer (24.2 vs. 17.9%, P=0.05). Notably, when stratification was performed by ER, PR and HER2 expression, the TGFBR2 -875A allele was found to correlate significantly to a decreased risk of breast cancer with ER(+) (OR=0.57, 95% CI 0.35-0.92), PR(+) (OR=0.54, 95% CI 0.34-0.88), ER(+)PR(+) (OR=0.55, 95% CI 0.33-0.92) and HER2(-) (OR=0.55, 95% CI 0.34-0.88) under a dominant genetic model. In conclusion, this is the first study to suggest that the TGFBR2 -875A allele modifies predisposition to breast cancer with an expression of ER(+), PR(+), ER(+)PR(+) and HER2(-).