谷胱甘肽转移酶T1和M1基因多态性及吸烟与结直肠癌关系的对照研究  

Associations between genetic polymorphisms of glutathione S-transferase M1 and T1,smoking and susceptibility to colorectal cancer: a case-control study

作　　者：陈坤[1] 蒋沁婷[1] 马新源 姚开颜 冷曙光[3] 俞维萍[1] 周海光[1] 

机构地区：[1]浙江大学医学院流行病与卫生统计教研室,杭州310031 [2]浙江嘉善县肿瘤研究所 [3]中国预防医学科学院劳动卫生与职业病研究所毒理室

出　　处：《中华肿瘤杂志》2004年第11期645-648,共4页Chinese Journal of Oncology

基　　金：国家自然科学基金资助项目 (3 0 170 82 8)

摘　　要：目的　研究谷胱甘肽转移酶 (GSTs)M1、T1基因多态性与结直肠癌易感性的关系。方法12 6例结直肠癌患者和 343例随机抽样的正常对照者 ,应用多重聚合酶链反应 (PCR)方法检测其GSTM1和GSTT1基因多态性 ,采用非条件Logistic回归模型分析基因型、吸烟情况与结直肠癌患病的关系。结果　GSTM1和GSTT1缺陷型基因型在对照人群中的频率分布为 5 5 .5 %和 2 0 .4 %。在GSTT1缺陷型基因型的人群中 ,GSTM1缺陷型患直肠癌风险是非缺陷型者的 9.74倍 (95 %CI为 1.13～83.85 )。现在吸烟者中 ,GSTM1缺陷型基因型患结肠癌的风险是非缺陷型者的 2 .2 2倍 (P >0 .0 5 ) ;GSTT1缺陷型基因型患结肠癌的风险是非缺陷型者的 4 .5 5倍 (95 %CI为 1.14～ 18.17) ,患直肠癌的风险是非缺陷型者的 4 .6 0倍 (95 %CI为 1.11～ 19.11)。结论　GSTM1和GSTT1缺陷型基因型有可能增加结直肠癌的危险性 ,其危险性主要表现在两者的联合作用上 ;环境暴露因素———吸烟和相关代谢酶多态性也表现出增加结直肠癌危险性的联合作用。Objective To evaluate the associations between genetic polymorphisms of glutathione S-transferase M1 and T1(GSTM1 and GSTT1), smoking and susceptibility to colorectal cancer. Methods A case-control study of 126 patients and 343 healthy controls was conducted to investigate the role of GSTM1 and GSTT1 polymorphisms in colorectal cancer. Genotypes of GSTM1 and GSTT1 polymorphisms were analyzed by multiplex allele-specific polymerase chain reaction (PCR). Results The frequencies of GSTM1 null and GSTT1 null genotypes were 55.5% and 20.4%, respectively. After adjustment for age and sex, among those with GSTT1 null genotype, the GSTM1 null genotype had a significant increased risk of rectal cancers compared to GSTM1 non-null genotype (OR=9.74, 95%CI, 1.13-83.85). A 2.22-fold risk of colon cancers was associated with GSTM1 null genotype compared to GSTM1 non-null genotype among current smokers (P>0.05). Individals with GSTT1 null genotype and currently smoking had a significant risk of colon cancers (OR=4.55, 95%CI, 1.14-18.17), and rectal cancers (OR=4.60, 95%CI, 1.11-19.11). Conclusion This study suggests that certain null GSTM1 and GSTT1 genotypes may be associated with an elevated risk of colorectal cancer which may be modified by interaction of the two genetic polymorphisms and cigarette smoking.

关 键 词：谷胱甘肽转移酶 结肠肿瘤 直肠肿瘤 吸烟 基冈多态性 易感性 

分 类 号：R735.3[医药卫生—肿瘤]