胸苷酸合成酶基因多态性与结直肠癌易感性的关系

目的研究胸苷酸合成酶（thymidylate synthase．TS）基因5＇-非翻译区（untranslated region，UTR）、3＇-UTR多态性及其与饮酒之间的联合作用和结直肠癌（colorectal cancer，CRC）易感性的关系。方法采用病例对照研究（140例病例和343例对照）设计，通过非条件Logistic回归模型和似然比检验分析TS上述多态性及其与饮酒之间的联合作用和CRC易感性之间的关系。结果单独的TS基因多态性与CRC之间无明显联系。两多态性之间联合作用的P值为0．05。无饮酒史者中，＋6bp等位基因是CRC的保护因素（OR=0．57．95％CI．0．32～0．99）．有饮酒史者中，＋6bp等位基因携带者患CRC的风险增加（OR=1．88，95％CI．0．80～4．41），并且随着饮酒年限的延长，OR值逐渐升高。似然比检验提示两者之间存在交互作用（P=0．01）。结论尚不能认为TS基因5LUTR和3LUTR多态性是CRC风险的独立预测因子，两多态性之间、3＇-UTR多态性与饮酒之间存在交互作用，共同改变个体罹患结直肠癌的风险。

Relationship between polymorphisms of thymidylate synthase gene and susceptibility of colorectal cancer

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.