Relationship between polymorphisms of thymidylate synthase gene and susceptibility of colorectal cancer / 中华消化杂志

ABSTRACT

Objectives To observe influences of two functionally important polymorphisms (5'-UTR and 3 -UTR) in thymidylate synthase (TS) gene and their combinative effects with drinking on the susceptibility of colorectal cancer (CRC). Methods A case-control study was designed, which included 140 CRC patients and 343 control subjects. Risk of CRC was estimated by unconditional Logistic model. Results The genotype distributions of the polymorphisms did not show significant differences between the cases and the controls. However, in those with -6 bp/-6 bp genotypes, the 2R carriers had a decreased risk (OR = 0. 60, 95%CI, 0. 23-1. 52) , but in +6 bp carriers, the 2R carriers had an elevated risk (OR=1. 87, 95%CI, 0. 94-3. 72). The likelihood test revealed the interaction existed between these two polymorphisms (P for interaction = 0. 05). Moreover, the combinative effect between the 3 -UTR polymorphism and alcohol drinking showed a significant association with the susceptibility of CRC (P for interaction =0. 01). In non-drinkers, the-6 bp allele carriers had a significant decreased risk (OR = 0. 57, 95%CI, 0. 32-0. 99) , but in ever and current drinkers, the +6 bp allele (6-bp insertion) carriers had an elevated risk (OR=1. 88, 95%CI, 0. 80-4. 41) , in which OR values ascended with the prolongation of drink-time. Conclusions The polymorphisms of thymidylate synthase at 5'-UTR and 3'-UTR may not be regarded as independent predictive factors for the susceptibility of CRC. However, interactions exist in these two polymorphisms and between the 3'-UTR polymorphism and drinking. Further studies with larger sample size and in different ethnic groups are needed.