GSTM1、GSTT1、GSTP1基因多态性与广东地区汉族人群喉癌遗传易感性关系的研究

The association between genetic polymorphisms of GSTM1、GSTT1、GSTP1 and susceptibility to laryngeal carcinoma from the Han people in Guangdong zone

目的:探讨毒物代谢酶GSTM1、GSTT1、GSTP1基因多态性与广东地区汉族人群喉癌遗传易感性的关系。方法:采用病例-对照研究的方法,运用PCR(多重PCR和ASA法)及PCR-RFLP、基因测序等技术检测233例广东地区汉族人群喉癌患者和102例健康对照组者外周血中GSTM1、GSTT1、GSTP1(Ⅰle/Ⅴal)基因的多态性。结合病历资料分析毒物代谢酶基因多态性与喉癌临床病理特征之间的关系。采用统计软件SPSS13.0处理数据,用Logistic回归模型进行因素间的相关检验,以OR值及其95%CI表示关联强度。结果:喉癌组GSTM1、GSTT1空白基因型频率显著高于对照组(OR=2.61、3.05,P<0.01)。重度吸烟与GSTT1空白基因型在喉癌致病中有协同作用(OR=3.51,95%CI为2.05～5.01;OR=2.99,95%CI为2.00～4.49)。有肿瘤家族史的患者GSTM1、GSTT1空白基因型比例较高。GSTM1、GSTT1空白基因型的患者晚期所占比例较大(P<0.05)。喉癌组与对照组中GSTP1多态基因频率差异无统计学意义。结论:GSTT1、GSTM1基因缺失与喉癌易感性关联,GSTT1空白基因型与吸烟特别是重度吸烟有协同作用而增加患癌易感性。GSTM1基因缺失致癌不与吸烟发生协同作用。GSTT1、GSTM1基因多态性可能影响喉癌的发展过程。GSTP1基因多态性可能与喉癌的遗传易感性无关。

Objective：To analyze the association between genetic polymorphisms of xenobiotic-metabolizing enzymes GSTM1,GSTT1,GSTP1 and susceptibility to laryngeal carcinoma from the Han people in Guangdong zone.Method：A case-control study was conducted involving 233 LSCC（laryngeal squamous cell carcinoma） patients and 102 healthy controls to investigate the association between polymorphisms of GSTM1,GSTT1,GSTP1（Ⅰle/Ⅴal）and LSCC from the Han people in Guangdong zone.All blood samples of the Han people from the Guangdong zone was analyszed with methods of PCR,ASA and the DNA sequencing technique with sequenator.We explored the association between polymorphisms and the clinical pathologic characteristics of LSCC.The data was processed with SPSS13.0.Odds Ratios（ORs） with 95% CI for relevancy intensity were calculated using binary logistic regression analysis.Result：The frequency of GSTM1（-） and GSTT1（-） genotype was higher in LSCC than that in healthy controls（OR=2.61,3.05,P〈0.01）.There was synergic effect between GSTT1（-） genotype and heavily smoking during carcinogenesis of LSCC（OR=3.51,95%CI=2.05-5.01;OR=2.99,95%CI=2.00-4.49）.The frequency of GSTM1（-） and GSTT1（-） genotype was higher in LSCC whose family had carcinoma history.The frequency of advanced LSCC was higher in patients who were with GSTM1（-） and GSTT1（-） genotype（P〈0.05）.There was no difference of the frequency of GSTP1（Ⅰle/Ⅴal） genotype between in LSCC and in healthy controls（P〉0.05）.Conclusion：There may be an association between the susceptibility to laryngeal carcinoma and GSTT1（-）,GSTM1（-） genotype.The GSTT1（-） polymorphismic gene cooperating with heavily smoking boost up the susceptibility of individual to laryngeal carcinoma.The GSTM1（-） polymorphismic gene may not cooperating with smoking during carcinogenesis of LSCC in the Han people in Guangdong zone.The polymorphisms of GSTT1 and GSTM1 gene may affect the carcino-genesis of LSCC in the Han people in Guangdong zone.There may be no association between the susceptibility to laryngeal carcinoma and the GSTP1（Ⅰle/Val） genotype.