TGF-α gene variations and increased susceptibility of gastric cancer in an Eastern Chinese Han population.

Transforming growth factor-alpha (TGF-α) correlates with deep invasion, advanced stage and poor prognosis in gastric cancer. Genetic variants in the 3' untranslated region (UTR) of TGF-α gene may influence the stability and post-transcriptional regulation of mRNA and contribute to gastric cancer predisposition. To test this hypothesis, we genotyped five polymorphisms in 3'UTR (rs3771527, rs503314, rs473698, rs3732253 and rs538118) and one in 3' near region (rs11466306) of the TGF-α gene by polymerase chain reaction-ligation detection reaction methods (PCR-LDR). We found that GA/AA genotype of rs11466306 in the 3' near gene could increase the risk of overall gastric cancer (adjusted OR = 1.499, 95%CI: 1.101-2.041), compared to the wild homozygous GG genotype. Meanwhile, the risk effect was more obvious in the intestinal gastric cancer and gastric noncardia cancer (adjusted OR = 1.682, 95%CI: 1.188-2.380; adjusted OR = 1.495, 95%CI: 1.072-2.086, respectively), but not for the diffuse type and gastric cardia cancer (p > 0.05). CT/TT genotype for rs3732253 in the 3' UTR was associated with increased risk of intestinal gastric cancer (adjusted OR = 1.464, 95%CI: 1.036-2.069), compared to their wild homozygous genotypes. These findings indicate that potentially functional TGF-α gene variant may contribute to the risk of intestinal gastric cancer and/or gastric noncardia cancer and could be used as molecular markers for detecting intestinal gastric cancer and/or gastric noncardia cancer in Chinese Han population.

Citation

Juan Wu, Shujuan Tong, Zhen Zhan, Junfeng Zhang, Che Chen, Shouyou Hu, Ruiping Wang. TGF-α gene variations and increased susceptibility of gastric cancer in an Eastern Chinese Han population. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 2014 Feb;19(1):9-15

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PMID: 24237184

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