The transforming growth factor beta (TGF-β) signaling pathway is critical for several important cellular functions, and plays dual roles in the carcinogenic process. We systematically evaluated associations of common variants in TGF-β signaling pathway genes with breast cancer risk using a multi-staged, population-based, case-control study among Chinese women. In Stage I, 341 single nucleotide polymorphisms (SNPs) with MAFs ≤ 0.05 across 11 genes were evaluated among 2,926 cases and 2,380 controls. In Stage II, 20 SNPs with promising associations were evaluated among an additional 1,890 cases and 2,000 controls. Six SNPs from the TGFB2, TGFBR1, TGFBR2 and TGFBR3 genes were found to have consistent and significant associations in combined analyses with breast cancer risk in combined analyses of Stage I and Stage II data. One variant, TGFBR2 rs1078985, had not only consistent, but also highly significant associations with breast cancer risk in both study stages, as well as promising results from in silico analysis, and so was further evaluated. Results from additional genotyping in Stage III (2,475 cases and 2,343 controls) were also consistent; compared with the major allele homozygotes (GG) of rs1078985, reduced breast cancer risks were associated with AA(OR=0.75, 95%CI=0.60-0.94) and AG (OR=0.89, 95%CI=0.82-0.96) genotypes (Ptrend =0.0003). These data support a role for common genetic variation in TGF-β signaling pathway genes, specifically for a variant in TGFBR2, in breast cancer susceptibility.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2604. doi:1538-7445.AM2012-2604