Variant alleles of TGFB1 and TGFBR2 are associated with a decreased risk of gastric cancer in a Chinese population

Abstract

Growing evidence suggests that the transforming growth factor b (TGF-b) signaling pathway occupies a central position in the signaling networks that control cell growth and differentiation. TGFb1 and its receptor TGF-bRII have been correlated with the development of certain forms of cancer, including gastric cancer. We hypothesized that functional genetic variants in TGFB1 and TGFBR2 are associated with gastric cancer risk. To test this hypothesis, we genotyped C-509T and Leu10Pro polymorphisms in TGFB1 and G-875A variant in TGFBR2, using the primer-introduced restriction analysis (PIRA)-PCR assay, in a case-control study of 675 gastric cancer cases and 704 healthy controls in a Chinese population. We found that the variant alleles of the promoter polymorphisms, TGFB1 C-509T and TGFBR2 G-875A, were associated with a significantly decreased risk of gastric cancer [adjusted odds ratio (OR) 5 0.65, 95% confidence interval (CI) 5 0.52-0.82 for 2509CT/TT and adjusted OR 5 0.67, 95% CI 5 0.53-0.85 for 2875GA/AA]. Furthermore, subjects with both variant genotypes of the TGFB1 C-509T and TGFBR2 G-875A were associated with a significantly (56%) decreased risk of gastric cancer (adjusted OR 5 0.44, 95% CI 5 0.32-0.62). These findings indicate, for the first-time, that the functional variants in the promoter of TGFB1 and TGFBR2 might contribute to gastric cancer susceptibility. ' 2006 Wiley-Liss, Inc.

Association between the TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms and gastric cancer: a case-control study

“…For the allele frequency of TGFBR2 -875A, similar frequencies were observed between Nanjing (0.197 in controls) and our population group (0.155 in controls) (8).…”

“…Allele frequency patterns of the TGFB1 -509C/T polymorphism vary greatly between different geographical regions and ethnic groups. For example, the frequencies of the -509 T allele among healthy controls were 0.468, 0.461 and 0.212 in Nanjing, Shandong and the uS population, respectively (8,9,12), while the -509 T allele frequency in our healthy controls was 0.572. As a result, the -509 T allele acted as a major allele in our region, but as a minor allele in the above-mentioned regions.…”

“…Li et al found that carriers of TGFB1 -509T were more susceptible to gastric cancer in northern China (9), which was consistent with our results (Table I). Jin et al reported that among a high-risk Chinese population in Nanjing, carriers of TGFB1 -509 T or TGFBR2 -875 A had a decreased risk of gastric cancer (8). On the other hand, no association was found between the TGFB1 -509C/T polymorphism and gastric cancer in a uS population (12).…”

“…TGFB1 -509C/T (rs1800469) and TGFBR2 -875A/G polymorphisms (rs3087465) have been reported to be associated with gastric cancer risk (8)(9)(10). However, the results of studies from different geographical regions, ethnic groups and study groups are controversial (8)(9)(10)(11)(12).…”

“…However, the results of studies from different geographical regions, ethnic groups and study groups are controversial (8)(9)(10)(11)(12). For example, certain studies found that carriers of TGFB1 -509T were associated with a decreased (8) or increased risk of gastric cancer (9).…”