Glutathione S-transferase M1 and T1 Gene Deletion Associated with Increased Susceptibility to Nasopharyngeal Carcinoma

Abstract

Objective: To evaluate the association of Glutathione S-transferase (GST) M1 and T1 genetic polymorphisms and susceptibility to nasopharyngeal carcinoma (NPC) in a high risk area of Guangxi Zhuang Autonomous Region (province), Southwest of China. Methods: A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (GSTM1 and GSTT1 null genotypes). A total of 127 NPC cases and 207 controls were recruited. Results: GSTM1 and GSTT1 null genotype frequencies were higher among NPC patients at a level of statistical significance (P <0.005; P <0.001 respectively), and both GSTM1 and GSTT1 null genotype were even more significant (P <0.001). Conclusion: NPC is the most common cancer in Guangxi. GST enzymes are involved in the detoxification of many environmental carcinogens. Homozygous deletions of GSTM1 and GSTT1 have been associated with several types of cancer. The risk to develop NPC has been associated with environmental factors such as cigarette smoking and EB virus infection. The present results indicate that the GSTM1 and GSTT1 deletion polymorphisms are associated with an increase risk of susceptibility to NPC, and both detoxific enzyme genes deletion is more important than a single gene deletion for the susceptibility to NPC.

A genome-wide association study identifies ITGA9 conferring risk of nasopharyngeal carcinoma

“…17,18 GSTM1 is a phase II enzyme known to detoxify several carcinogens, including those found in tobacco smoke, and homozygous deletions of GSTM1 are associated with an increased risk of NPC. 19 The CYP2E1 and CYP2A6 enzymes are known to activate nitrosamines and related carcinogens, and are possibly involved in the development of this disease. Certain variants of the CYP2E1 and CYP2A6 genes are thought to be more highly expressed than others and thus induce higher levels of cellular damage.…”

Quantitative assessment of the association between glutathione S-transferase M1 polymorphism and the risk of developing nasopharyngeal cancer

“…The initial search yielded 394 study titles and abstracts, which were then subjected to an independent review. Based on the inclusion criteria, 12 individual publications studying the association of the GSTM1 polymorphism and the risk of developing NPC in a total of 1,593 cases and 2,868 individuals were available for analysis (9,(11)(12)(13)(14)(15)(16)(17)(20)(21)(22). The clinical characteristics of these studies are listed in Table I.…”

“…P<0.01 and I 2 >50% were considered to indicate a statistically significant difference in heterogeneity (26,27). Subgroup analyses were also conducted according to ethnicity: Of the 12 included studies, 10 were conducted in Asians (11)(12)(13)(14)(15)(16)18,(20)(21)(22), 1 in North Africans (17) and 1 in a mixed population (9). Publication bias was evaluated by funnel plot (28) and Egger's linear regression test (29).…”

“…The GSTM1 null variant may lead to the absence of enzymatic activity, and individuals who carry this variant are thought to be at increased risk of developing cancer (6). Numerous studies have previously evaluated the association of the GSTM1 polymorphism with the susceptibility to NPC, but the results are inconsistent, possibly due to the limited sample size and low power of these studies, which are insufficient to detect the precise effect in a single study (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). Thus, in the present study, a meta-analysis was performed in order to quantitatively evaluate the association between the GSTM1 polymorphism and the susceptibility to NPC.…”

Association Between GSTM1 Polymorphism and Nasopharyngeal Cancer Susceptibility: a Meta-analysis

“…A total of 34 potentially relevant publications up to September 6, 2012 were systematically identified by searching Pubmed, Embase, ISI Web of Science, and Wanfang databases. According to the inclusion criteria, 11 published case-control studies with 1,513 cases and 2,802 controls were included into this meta-analysis (Nazar-Stewart et al, 1999;Da et al, 2002;Cheng et al, 2003;Liu et al, 2003;Deng et al, 2004;Deng et al, 2005;Tiwawech et al, 2005;Bendjemana et al, 2006;Guo et al, 2008;Jiang et al, 2011;Wei et al, 2012), while the other 23 ones were finally excluded because they did not examine the relationship of GSTM1 polymorphism with NPC risk or they were reviews. Two of the 11 publications (Deng et al, 2004;Deng et al, 2005) had the same first author, however, the both were considered as two separate study because they were not based on the same participants with NPC.…”