GSTM1、GSTT1基因多态性和吸烟与膀胱癌关系的病例对照研究

Polymorphisms of GSTM1 and GSTT1 with smoking and bladder cancer risk: a population-based case control study

目的:应用全人群为基础的病例对照研究探讨GSTM1、GSTT1基因多态性和吸烟与膀胱癌危险性的关系。方法:采用多重PCR方法对404例正常对照和414例膀胱癌病例的基因组DNA进行GSTM1和GSTT1基因分型,应用非条件logistic回归分析方法进行统计分析。结果:与携带GSTM1(+)基因型者比,GSTM1(-)基因型的男、女性患膀胱癌危险性分别为1.66(95%CI:1.18～2.33)和1.08(95%CI:0.59～1.98)。同样携带GSTM1(-)基因型,吸烟者比不吸烟者患膀胱癌的危险性更加明显。与不吸烟且携带GSTM1(+)基因型男性比,GSTM1(-)基因型的目前吸烟者的OR值为2.99(95%CI:1.56～5.74),而携带GSTM1(-)基因型同时吸烟年限≥40年者OR为4.33(95%CI:2.14～8.73)。尽管女性吸烟例数较少,但携带GSTM1(-)基因型的吸烟女性患膀胱癌危险性显著高于不吸烟的GSTM1(+)基因型者,OR值为6.72(95%CI:1.69～26.80)。与不吸烟且携带GSTT1(+)基因型男性相比,携带GSTT1(-)基因型的吸烟者患男性膀胱癌危险的OR值为1.38(95%CI:0.79～2.42)。携带GSTT1(-)基因型的吸烟女性患膀胱癌危险性是不吸烟的GSTT1(+)基因型者的3.04倍(95%CI:0.77～12.01)。结论:GSTM1(-)基因型能显著增加男性患膀胱癌的风险,该基因型与吸烟可能有一定的联合作用。GSTT1基因型可能与上海市区男、女性膀胱癌无关。

Objective：To evaluate the relationship between genetic polymorphisms of glutathione S-transferase mu （GSTM） 1 and glutathione S-transferase theta （GSTT）1 and smoking and bladder cancer risk from a population-based case control study. Methods： The GSTM1 and GSTT1 genotypes were determined by multiplex PCR analysis in 414 bladder cancer patients and 404 population controls. The association between the genotypes and bladder cancer risk was measured by odds ratios （ORs） and 95 confidence intervals （95% CIs）. The ORs and 95% Cls were calculated by unconditional logistic regression, Results： Compared with the GSTM1 （＋） genotypes, the GSTM1 （-） genotype was associated with an increased risk of bladder cancer in men （OR. 1.66,95% CI 1.18-2.33 ）, but not in women （OR ： 1.08,95% CI. 0.59-1.98）. The increased risk of bladder cancer associated with GSTM（-） genotype was more apparent in smokers than that in nonsmokers. Compared with GSTM1 （＋） male nonsmokers, the ORs （95% CIs） were 2.99 （1, 56-5.74） for current GSTMI（-） smokers and 4.33（2.14-8.73） for GSTMI（-） heavy smokers with smoking history of more than 40 years. Ahhough few women smoked cigarettes, the risk of bladder cancer in GSTM1（-） female smokers was significantly elevated compared with GSTM1（＋） female nonsmokers （OR：6. 72, 95%CI： 1.69-26.80）. Compared with GSTT1 （＋） male non-smokers, the risk of bladder cancer in GSTT1 （-） male smokers was increased （OR： 1.38, 95% CI： 0. 79-2.42）, The risk of bladder cancer in GSTT1 （-） female smokers was higher than GSTT1 （ ＋ ） female non-smokers （OR ： 3.04, 95% CI： 0.77-12.01 ）. Conclusion： GSTM1 null genotype was associated with an increased risk of bladder cancer,especially for smokers, GSTT1 genotypes might have no association with risk of bladder cancer in both male and female patients in urban Shanghai.