Abstract
BackgroundThe genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population.MethodsData on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1) from 68 studies, glutathione S-transferase theta 1 (GSTT1) from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk. Odds ratios (OR) were pooled using forest plots. 9 subgroups were all or partly performed in the subgroup analyses. The Galbraith plot was used to identify the heterogeneous records. Potential publication biases were detected by Begg's and Egger's tests.Results71 eligible studies were identified after screening of 1608 articles. The increased association between two vital GSTs genetic polymorphisms and lung cancer risk was detected by random-effects model based on a comparable heterogeneity. Subgroup analysis showed a significant relationship between squamous carcinoma (SC), adenocarcinoma (AC) or small cell lung carcinoma (SCLC) and GSTM1 null genotype, as well as SC or AC and GSTT1 null genotype. Additionally, smokers with GSTM1 null genotype had a higher lung cancer risk than non-smokers. Our cumulative meta-analysis demonstrated a stable and reliable result of the relationship between GSTM1 null genotype and lung cancer risk. After the possible heterogeneous articles were omitted, the adjusted risk of GSTs and lung cancer susceptibility increased (fixed-effects model: ORGSTM1 = 1.23, 95% CI: 1.19 to 1.27, P<0.001; ORGSTT1 = 1.18, 95% CI: 1.10 to 1.26, P<0.001; ORGSTM1-GSTT1 = 1.33, 95% CI: 1.10 to 1.61, P = 0.004).ConclusionsAn increased risk of lung cancer with GSTM1 and GSTT1 null genotype, especially with dual null genotype, was found in the Chinese population. In addition, special histopathological classification of lung cancers and a wide range of gene-environment and gene-gene interaction analysis should be taken into consideration in future studies.
Highlights
Lung cancer is the most common malignancy in the world and the leading cancer in males, accounting for 17% of the total new cancer cases and 23% of the total cancer deaths [1,2,3]
Literature research strategy A computer-based literature search was carried out in EMBASE, PubMed, ISI Web of Knowledge, Chinese Biomedical Database (CBM), VIP database, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data to collect articles related to the association of glutathione S-transferase Mu 1 (GSTM1) and/or glutathione Stransferase theta 1 (GSTT1) polymorphisms and lung cancer susceptibility in the Chinese population
Study selection and study characteristics We identified a total of 71 articles [54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124] reporting the relationship between GSTM1 and/or GSTT1 genetic polymorphisms and lung cancer risk from both Chinese and English databases (Figure 1)
Summary
Lung cancer is the most common malignancy in the world and the leading cancer in males, accounting for 17% of the total new cancer cases and 23% of the total cancer deaths [1,2,3]. The burden of lung cancer mortality in females in developing countries is up to 11% of the total female cancer deaths [2]. In China, females have a lower prevalence of smoking, there is still higher lung cancer rates (21.3 cases per 100,000 females) than those in European countries [5], due to indoor air pollution, cooking fumes, occupational and environmental pollutions. Due to the incurable nature and less than a five-year survival rate (only 16%), lung cancer has attracted a huge attention across the whole world [6]. The genetic polymorphisms of glutathione S-transferase (GSTs) have been suspected to be related to the development of lung cancer while the current results are conflicting, especially in the Chinese population
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