FAS和FASL基因多态性增加乳腺癌发病风险

Polymorphisms in FAS and FASL Contribute to Increased Risk of Breast Cancer

目的:检测F4S(-1377G/A和-670A/G)和FASL基因(-844T/C和7896G/C)多态与乳腺癌发病风险的关系。方法:本研究设计了包括840例乳腺癌患者和840例正常人对照的病例-对照研究确定这两个基因多态对乳腺癌发病风险的影响。结果:携带FAS-1377AA(OR,1.36;95%CI,1.01～1.82;P=0.045)和GA(OR,1.29;95%CI,1.05～1.59;P=0.017)者以及FASL-844CC(OR,1.53;95%CI,1.01～2.31;P=0.045)基因型者发生乳腺癌的风险增高,同时携带FAS-1377AA和FASL-844CC基因型者乳腺癌发病风险显著增高(OR,3.00;95%CI,1.45～6.24;P=0.003)。携带FAS-1377A/-670A单体型者发生乳腺癌的风险高于携带FAS-1377G/-670A单体型者(OR,1.45;95%CI,1.06～2.00;P=0.021),但是携带FAS-1377G/-670G单体型者发生乳腺癌的风险则低于FAS-1377G/-670A单体型携带者(OR,0.68;95%CI,0.49～0.93;P=0.016)。携带FASL-844T/7896C单体型者发生乳腺癌的风险低于FASL-844C/7896G单体型携带者(OR,0.79;95%CI,0.67～0.94;P=0.009)。结论:FAS-FASL系统的功能性遗传多态性可能与乳腺癌的发病风险增加有关。

Objective： To exam the effects of EAS （-1377G/A and -670A/G） and FASL （-844T/C and 7896G/C） polymorphisms on the risk of developing breast cancer. Methods： To determine the association between FAS or FASL genotype and risk of developing breast cancer. we designed a case-control study consisting of 840 patients with breast cancer and 840 cancer-free controls. Results： Subjects carrying the FAS-1377AA （OR, 1.36; 95% CI. 1.01-1.82; P =0.045）. GA（OR, 1.29： 95% CI. 1.05-1.59： P =0.017） genotypes and FASL -844CC （OR. 1.53： 95% CI. 1.01-2.31; P = 0.045） genotype had a moderately excessive risk of developing breast cancer. By examing interaction between the FAS and FASL. polymorphisms in risk of breast cancer, no data shown any significant interaction between the polymorphisms in these two genes except subjects carrying the FAS -1377AA and FASL --844CC genorypes （OR, 3.00： 95% CI=1.45-6.24; P=0.003）. In addition, subjects carrying the EAS -1377A/-670A hapiotype had a higher risk for breast cancer compared with those with the E4S -1377G/-670A haplotype （OR, 1.45; 95% CL 1.06-2.00; P = 0.021 ） but the FAS -1377G/-670G haplotype had a lower （OR, 0.68; 95% CI. 0.49-0.93; P = 0.016） risk compared with the EAS -1377G/-670A haplotype. For the FASL polymorphisms, the -844T/7896C haplotype was associated with a significantly lower risk compared with the -844C/7896G haplotype （OR. 0.79： 95% CI. 0.67-0,94; P =0.009）. Conclusion These findings indicated that genetic polymorphisms in the FAS-FASL system may confer host susceptibility to breast cancer .