Abstract
To evaluate the relationship between polymorphisms (28 bp repeated sequences in 5'-UTR and 6-bp ins/ del in 3'-UTR) in then thymidylate synthetase gene (TS) and risk of colorectal, colon and rectal cancers, we conducted a case-control study with 315 cases of colorectal cancer and 439 population-based controls in Jiangsu province, China. TS genotypes were identified using PCR-RFLP (restriction fragment length polymorphism) methods. Odds ratios (ORs) were estimated with an unconditional logistic regression model. We found that the distributions of 5'-UTR genotypes in TS were significantly different between controls and male colon cases (χ2 =8.25, P = 0.016). Compared with 3R/3R genotype, individuals with the 2R allele were at an increased risk of colon cancer (age-, BMI-, smoking- and alcohol drinking-adjusted OR=1.98, 95%CI: 1.11-3.53) among men. In contrast, the 6-bp ins/del polymorphism at the TS 3'- UTR did not influence risk of the colorectal, colon and rectal cancers. When combined genotypes for both TS 5'-UTR and 3'-UTR polymorphisms were evaluated, individuals with the 5'-UTR 2R allele had a OR of 3.61 (95%CI: 1.38-9.49) for colon cancer among men with the 3'-UTR -6bp/-6bp genotype. These results show that the polymorphism of the 28 bp repeated sequences in TS 5'-UTR could influence susceptibility to colon cancer and that there was a coordinated effect between TS 3'-UTR and 5'-UTR polymorphisms in increasing risk of colon cancer among Chinese men.
Highlights
When combined genotypes for both thymidylate synthetase gene (TS) 5’-UTR and 3’-untranslated region (3’-UTR) polymorphisms were evaluated, individuals with the 5’-UTR 2R allele had a Odds ratios (ORs) of 3.61 (95%CI: 1.38-9.49) for colon cancer among men with the 3’-UTR –6bp/-6bp genotype. These results show that the polymorphism of the 28 bp repeated sequences in TS 5’-UTR could influence susceptibility to colon cancer and that there was a coordinated effect between TS 3’-UTR and 5’-UTR polymorphisms in increasing risk of colon cancer among Chinese men
Thymidylate synthetase (TS) is a key enzyme in folate metabolism catalysing the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate, providing the sole de novo source of thymidine required for DNA synthesis and repair (Choi et al, 2000)
Ulrich et al (2000) identified a 6-bp ins/del variation at bp 1494 in the 3’-untranslated region (3’-UTR) of the TS mRNA by screening public databases of the expressed sequence tag
Summary
Thymidylate synthetase (TS) is a key enzyme in folate metabolism catalysing the conversion of deoxyuridine monophosphate to deoxythymidine monophosphate, providing the sole de novo source of thymidine required for DNA synthesis and repair (Choi et al, 2000). To evaluate the relationship between polymorphisms (28 bp repeated sequences in 5’-UTR and 6-bp ins/ del in 3’-UTR) in thymidylate synthetase gene (TS) and risk of colorectal, colon and rectal cancers, we conducted a case-control study with 315 cases of colorectal cancer and 439 population-based controls in Jiangsu province, China. We found that the distributions of 5’-UTR genotypes in TS were significantly different between controls and male colon cases (χ2 =8.25, P = 0.016).
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