Guo Xiuchan, O'Brien Stephen J, Zeng Yi, Nelson George W, Winkler Cheryl A
State Key Laboratory for Infectious Diseases Prevention and Control, Institute for Viral Disease Control and Prevention, Chinese CDC, Beijing, China.
Cancer Epidemiol Biomarkers Prev. 2008 Jul;17(7):1760-3. doi: 10.1158/1055-9965.EPI-08-0149.
Southern China is a major nasopharyngeal carcinoma-endemic region. Environmental factors and genetic susceptibility contribute to nasopharyngeal carcinoma development in this area. Polymorphic deletions of GSTM1 and GSTT1 genes involved in the detoxification of potentially carcinogenic agents may be a risk factor for nasopharyngeal carcinoma. To investigate the roles of genetic variations of GSTM1 and GSTT1 in nasopharyngeal carcinoma susceptibility in the Chinese population, we conducted a case-control study of 350 nasopharyngeal carcinoma cases and 622 controls. GSTM1 and GSTT1 deletion variants were genotyped by multiplex PCR assays. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals (95% CI). No significant association was observed for either GSTM1- or GSTT1-null genotype independently in the contribution to nasopharyngeal carcinoma risk. To explore possible joint effects of the GSTM1- and GSTT1-null polymorphisms with each other and with other risk factors for nasopharyngeal carcinoma, we examined the association between each combined genotype and the risk for nasopharyngeal carcinoma stratified by gender and EBV replication status. We found that individuals who carried GSTM1/GSTT1-double null genotype had a higher risk for nasopharyngeal carcinoma in the male population (odds ratio, 1.76; 95% confidence interval, 1.04-2.97; P = 0.03); however, this was not significant after correction for multiple comparisons. No statistical difference was found between cases and controls in females and the subpopulation positive for immunoglobulin A antibodies to EBV capsid antigen for combined genotypes. Our results suggest that the GSTM1/GSTT1-double null genotype may be a risk factor for nasopharyngeal carcinoma among males in southern China, but this result warrants confirmation in other studies.
中国南方是鼻咽癌的主要高发地区。环境因素和遗传易感性促使该地区鼻咽癌的发生。参与潜在致癌物质解毒的GSTM1和GSTT1基因的多态性缺失可能是鼻咽癌的一个危险因素。为了研究GSTM1和GSTT1基因变异在中国人群鼻咽癌易感性中的作用,我们对350例鼻咽癌患者和622例对照进行了病例对照研究。通过多重PCR检测对GSTM1和GSTT1缺失变异进行基因分型。采用逻辑回归分析估计比值比和95%置信区间(95%CI)。在对鼻咽癌风险的贡献方面,未观察到GSTM1或GSTT1基因缺失型单独存在显著关联。为了探讨GSTM1和GSTT1基因缺失多态性相互之间以及与其他鼻咽癌危险因素可能的联合作用,我们按性别和EBV复制状态分层,研究了每种联合基因型与鼻咽癌风险之间的关联。我们发现,携带GSTM1/GSTT1双基因缺失型的男性人群患鼻咽癌的风险较高(比值比,1.76;95%置信区间,1.04 - 2.97;P = 0.03);然而,在进行多重比较校正后,这一结果并不显著。在女性以及EBV衣壳抗原免疫球蛋白A抗体呈阳性的亚组人群中,病例组和对照组在联合基因型方面未发现统计学差异。我们的结果表明,GSTM1/GSTT1双基因缺失型可能是中国南方男性鼻咽癌的一个危险因素,但这一结果有待其他研究证实。