Pathway analyses identify TGFBR2 as potential breast cancer susceptibility gene: results from a consortium study among Asians.
نویسندگان
چکیده
BACKGROUND The TGF-β signaling pathway plays a significant role in the carcinogenic process of breast cancer. METHODS We systematically evaluated associations of common variants in TGF-β signaling pathway genes with breast cancer risk using a multistage, case-control study among Asian women. RESULTS In the first stage, 341 single-nucleotide polymorphisms with minor allele frequencies ≥ 0.05 across 11 genes were evaluated among 2,926 cases and 2,380 controls recruited as a part of the Shanghai Breast Cancer Genetics Study (SBCGS). In the second stage, 20 SNPs with promising associations were evaluated among an additional 1,890 cases and 2,000 controls from the SBCGS. One variant, TGFBR2 rs1078985, had highly consistent and significant associations with breast cancer risk among participants in both study stages, as well as promising results from in silico analysis. Additional genotyping was carried out among 2,475 cases and 2,343 controls from the SBCGS, as well as among 5,077 cases and 5,384 controls from six studies in the Asian Breast Cancer Consortium (stage III). Pooled analysis of all data indicated that minor allele homozygotes (GG) of TGFBR2 rs1078985 had a 24% reduced risk of breast cancer compared with major allele carriers (AG or AA; OR, 0.76; 95% CI, 0.65-0.89; P = 8.42 × 10(-4)). CONCLUSION These findings support a role for common genetic variation in TGF-β signaling pathway genes, specifically in TGFBR2, in breast cancer susceptibility. IMPACT These findings may provide new insights into the etiology of breast cancer as well as future potential therapeutic targets.
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عنوان ژورنال:
- Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
دوره 21 7 شماره
صفحات -
تاریخ انتشار 2012