Abstract
Objective: To study the influence of GSTM1 and GSTT1 gene polymorphisms on cervical cancer (CC) risk, and explore genetic-environmental interactions. Methods: After a systematic literature search, all relevant studies entailing the association between GST polymorphisms and CC were included. The pooled odds ratio (OR) was used for analysis of the results and corresponding 95% confidence intervals (CI) were estimated. Results: A total of 23 case-control studies were included in the meta-analysis of GSTM1 (2,250 CC cases and 3,025 controls) and GSTT1 (1,704 CC cases and 2,460 controls) genotypes. For the GSTM1 polymorphisms, the null genotype of GSTM1 was associated with an increased CC risk for the total population (OR=1.57, 95% CI=1.25-1.98). A similar association was found in China (OR=2.34, 95% CI=1.56-3.52), India (OR=2.02, 95% CI=1.43-2.83), Pakistan (OR=5.52, 95% CI=2.34-13.07), Serbia (OR=1.73, 95% CI=0.68-4.39) and Kazakhstan (OR=6.5, 95% CI=2.25-18.81), but was not noted for others countries. Regarding human papilloma virus (HPV) infection, moderately but significantly increased risk of the null GSTM1 genotype was found in HPV-positive patients (OR=2.59, 95% CI=1.57-4.27). For the GSTT1 polymorphisms, the null GSTT1 genotype was associated with increased CC risk in the total population (OR=1.44, 95% CI=1.07-1.93). Regarding ethnic stratification, a significantly increased risk of the null GSTT1 genotype was found in Kazakhstan (OR=3.99, 95% CI=2.56-6.21) and Brazil (OR=4.58, 95% CI=2.04-10.28). With respect to smoking, the two aspects of the analysis above were not significantly associated with CC risk in smokers or non-smokers, respectively. For the GSTM1/GSTT1 interaction analysis, the dual null genotypes of GSTM1/GSTT1 were significantly associated with increased CC risk for the total population (OR=1.62, 95% CI=1.14-2.29). Conclusion: This meta-analysis provided sufficient evidence that the null genotype of GSTM1, or GSTT1 and the dual-null genotypes of GSTM1/GSTT1 are associated with CC.
Highlights
Cervical cancer (CC), which has an annual global incidence of 530,000 new cases, is the second most commonly diagnosed cancer and third leading cause of cancer death among females in less developed countries
The overall results showed that the null genotype of glutathione S-transferase mu 1 (GSTM1) was related to increased risk of CC (OR=1.57, 95% confidence intervals (CI)=1.25-1.98, p
In the subgroup analysis for ethnicity, the result showed that the null genotype of GSTM1 was associated with an increased CC risk in China (OR=2.34, 95% CI=1.56-3.52, p
Summary
Cervical cancer (CC), which has an annual global incidence of 530,000 new cases, is the second most commonly diagnosed cancer and third leading cause of cancer death among females in less developed countries. Cervical cancer is predominantly attributed to infection accounting for 100% of cases worldwide [1]. 90% of cervical cancer deaths occurred in developing parts of the world: 60,100 deaths in Africa, 28,600 in Latin America and the Caribbean, and 144,400 in Asia. The second most populous country in the world, accounted for 25% of cervical cancer deaths (67,500 deaths). In Eastern, Middle, and Southern Africa as well as in Melanesia, cervical cancer is the leading cause of cancer deaths in females [2]. We concluded that CC may not be caused by one single factor; rather that genetic and environmental factors may play important roles in cervical cancer
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