凋亡相关基因FAS及其配体FASL基因单核苷酸多态与大肠癌风险

Genetic polymorphisms of apoptosis-associated genes FAS and FASL and risk of colorectal cancer

目的凋亡相关基因FAS及其配体FASL系统与肿瘤发生关系密切。本研究主要探讨FAS1377G/A和FASL844T/C多态与大肠癌风险的关系。方法采用聚合酶链反应(PCR)和限制性片段长度多态性(RFLP)分析方法,检测了382例大肠癌患者和648例配对的正常对照者FAS1377G/A和FASL844T/C多态基因型,比较不同基因型与大肠癌发生的关系。结果与FAS1377GG基因型和FASL844TT基因型者相比,FAS1377AA基因型和FASL844CC基因型携带者罹患大肠癌的风险分别增加了64.0%(95%CI,1.11～2.44)和69.0%(95%CI,1.03～2.78)。同时,我们发现这两个多态在大肠癌发生过程中存在明显的基因基因交互作用,同时携带FAS1377AA和FASL844CC基因型者发生大肠癌的风险是同时携带FAS1377GG/GA和FASL844TT/TC基因型者的3.6倍(95%CI,2.09～3.60)。结论凋亡相关基因FAS1377G/A及其配体FASL844T/C多态可能是中国人大肠癌的遗传易感因素。

Objective The FAS and FASL system plays a key role in regulating apoptotic cell death and corruption of this signaling pathway has been shown to participate in tumorigenesis. We previously have shown that the FAS-1377G/A and FASL-844T/C polymorphisms are associated with esophageal cancer. This case-control study was to examine the contribution of the polymorphisms to susceptibility of colorectal cancer.Methods PCR-RFLP method was used to determine the genotypes of FAS-1377G/A and FASL-844T/C in 382 patients with colorectal cancer and 648 controls. The adjusted odds ratios （ORs） and 95% confidence intervals （CIs） were calculated using logistic regression model. Results The subjects with the AA genotype of FAS-1377G/A and CC genotype of FASL-844T/C had an increased risk for colorectal cancer compared with those with the FAS-1377GG genotype （ adjusted OR, 1.65 ; 95% CI, 1.14-2. 38 ） and FASL-844TT genotype （adjusted OR, 1.76; 95% CI, 1.37-2.28 ）. Furthermore, the effect of FAS and FASL polymorphisms on risk of colorectal cancer displayed a significantly gene-gene interaction （liklihood ratio test, P = 0. 002）. Conclusion These findings suggest that the FAS-1377G/A and FASL-844T/C polymorphisms may be genetic susceptibility factors for colorectal cancer among Chinese population.