title: Association between the TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms and gastric cancer: a case-control study.
abstract: The transforming growth factor-β (TGFβ) pathway plays an important role in various types of human cancer. However, the role of TGFB1 -509C/T and TGFBR2 -875A/G polymorphisms in gastric cancer is controversial. We aimed to investigate the associations between these polymorphisms and gastric cancer susceptibility, clinicopathological parameters and survival. A case-control study was conducted in 1,010 gastric cancer patients and 1,500 healthy controls. Genotypes were determined by PCR-restriction fragment length polymorphism and DNA sequencing. Compared with the TT genotype, the TGFB1 -509 C allele (CT/CC) was significantly associated with a reduced risk of gastric cancer (OR, 0.71; 95% CI, 0.58-0.87; p=0.001) and certain subtypes of gastric cancer including intestinal type (OR, 0.70; 95% CI, 0.57-0.87; p=0.001), poorly differentiated (OR, 0.67; 95% CI, 0.54-0.85; p=0.001) and stage TNM III+IV (OR, 0.73; 95% CI, 0.58-0.92; p=0.008). Compared with the TGFBR2 -875 GG genotype, carriers of the A allele (AA/AG) had a significantly decreased gastric cancer risk (OR, 0.58; 95% CI, 0.62-0.91; P<0.001). A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles was associated with a further decreased risk of gastric cancer (OR, 0.42; 95% CI, 0.32-0.57, p<0.001). No significant correlation was observed between polymorphisms and survival of gastric cancer patients. Our results suggest that both the TGFB1 -509 and TGFBR2 -875 polymorphisms contribute to a decreased gastric cancer risk. The TGFB1 -509 polymorphism affects certain subtypes of gastric cancer according to clinicopathological parameters. A combination of the TGFB1 -509 C and TGFBR2 -875 A alleles conferred a further decreased gastric cancer risk. These findings provide clues to the biological mechanisms that underline tumor heterogeneity.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou.
authors.forename: Lixia
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authors.lastname: Xu
authors.forename: Zhirong
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authors.lastname: Zeng
authors.forename: Bin
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authors.lastname: Chen
authors.forename: Xiaoqin
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authors.lastname: Wu
authors.forename: Jun
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authors.lastname: Yu
authors.forename: Ling
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authors.lastname: Xue
authors.forename: Linwei
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authors.lastname: Tian
authors.forename: Yiming
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authors.lastname: Wang
authors.forename: Minhu
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authors.lastname: Chen
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.forename: Pinjin
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authors.lastname: Hu