Sun Zhen-Feng, Zhang Jia, Xu Hong-Ming, Wang Guo-Liang, Dong Pin
Department of Otorhinolaryngology, Shanghai First People's Hospital, Shanghai, China.
Asian Pac J Cancer Prev. 2012;13(11):5817-21. doi: 10.7314/apjcp.2012.13.11.5817.
BACKGROUND/AIMS: Glutathione S-transferase M1 (GSTM1) is a multifunctional enzyme that plays a critical role in the detoxification of varieties of carcinogenic metabolites. Many studies have been conducted to investigate the association between GSTM1 polymorphism and nasopharyngeal cancer (NPC) risk, but the findings among those studies are inconsistent. To assess this relationship more precisely, we performed a meta-analysis of all available studies on the subject.
Case-control studies were identified by searching Pubmed, Embase, ISI Web of Science, and Wanfang databases through September 6, 2012. We used the pooled odds ratio (OR) with its corresponding 95% confidence interval (95%CI) to evaluate the association of GSTM1 polymorphism with NPC susceptibility. Subgroup analyses by pathological types, sex and smoking status were performed to further identify the association.
Overall, 11 published studies with 1,513 cases and 2,802 controls were finally included into this meta-analysis according to the inclusion criteria. Meta-analysis of total studies showed that the null genotype of GSTM1 was significantly associated with increased risk of NPC, when comparing with the non-null genotype (OR=1.51, 95%CI=1.33-1.72, POR<0.001). The association was still statistically significant in subgroup analysis of patients with nasopharyngeal squamous cell carcinoma (OR=1.73, 95%CI=1.24-2.42, POR=0.001). Males with the null genotype of GSTM1 were more likely to subject to NPC than females. In addition, the association between the null genotype of GSTM1 and NPC risk was strongest in individuals with exposure to smoking. Sensitivity analysis by sequential omission of any individual studies one at a time further demonstrated the significant association.
The findings suggest that the null genotype of GSTM1 is a risk factor for NPC, and there is a gene- smoking interaction in this association.
背景/目的：谷胱甘肽S-转移酶M1（GSTM1）是一种多功能酶，在多种致癌代谢物的解毒过程中起关键作用。已经开展了许多研究来调查GSTM1基因多态性与鼻咽癌（NPC）风险之间的关联，但这些研究的结果并不一致。为了更精确地评估这种关系，我们对该主题的所有现有研究进行了荟萃分析。
通过检索截至2012年9月6日的Pubmed、Embase、ISI Web of Science和万方数据库来确定病例对照研究。我们使用合并比值比（OR）及其相应的95%置信区间（95%CI）来评估GSTM1基因多态性与NPC易感性之间的关联。通过病理类型、性别和吸烟状况进行亚组分析，以进一步确定这种关联。
总体而言，根据纳入标准，最终有11项已发表的研究（1513例病例和2802例对照）被纳入该荟萃分析。对所有研究的荟萃分析表明，与非无效基因型相比，GSTM1的无效基因型与NPC风险增加显著相关（OR=1.51，95%CI=1.33-1.72，P<0.001）。在鼻咽鳞状细胞癌患者的亚组分析中，这种关联仍然具有统计学意义（OR=1.73，95%CI=1.24-2.42，P=0.001）。GSTM1无效基因型的男性比女性更易患NPC。此外，在吸烟人群中，GSTM1无效基因型与NPC风险之间的关联最强。通过一次逐一剔除任何一项个体研究进行敏感性分析，进一步证实了这种显著关联。
研究结果表明，GSTM1的无效基因型是NPC的一个危险因素，并且在这种关联中存在基因-吸烟相互作用。
