Association between glutathione S-transferase T1 null genotype and risk of lung cancer: a meta-analysis of 55 studies

Yang, Hongmei; Shen, Xiaoyu; Li, Binru; Ma, Rui

doi:10.1007/s13277-013-1311-0

Cited by 6 publications

(10 citation statements)

References 54 publications

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“…Overall there was an eight-fold difference in urinary SPMA at baseline between subjects who had both or neither GSTM1 and GSTT1 genes. The deletion polymorphism of GSTM1 and GSTT1 genes is associated with increased risk of many malignancies including lung cancer (33), particularly in smokers (34). The present study demonstrates that smokers lacking both GSTM1 and GSTT1 genes may derive the most benefit from intake of PEITC due to their increased detoxification of carcinogens and toxicants.…”

Section: Discussionmentioning

confidence: 99%

2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke

Yuan

Murphy

Stepanov

et al. 2016

Cancer Prevention Research

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Cigarette smoke contains relatively large quantities of volatile organic toxicants or carcinogens such as benzene, acrolein and crotonaldehyde. Among their detoxification products are mercapturic acids formed from glutathione conjugation, catalyzed in part by glutathione S-transferases (GST). A randomized phase 2 clinical trial with a crossover design was conducted to evaluate the effect of 2-phenethyl isothiocyanate (PEITC), a natural product formed from gluconasturtiin in certain cruciferous vegetables, on the detoxification of benzene, acrolein, and crotonaldehyde in 82 cigarette smokers. Urinary mercapturic acids of benzene, acrolein and crotonaldehyde at baseline and during treatment were quantified. Overall, oral PEITC supplementation increased the mercapturic acid formed from benzene by 24.6% (P=0.002) and acrolein by 15.1% (P=0.005), but had no effect on crotonaldehyde. A remarkably stronger effect was observed among subjects with the null genotype of both GSTM1 and GSTT1: in these individuals PEITC increased the detoxification metabolite of benzene by 95.4% (P<0.001), of acrolein by 32.7% (P=0.034), and of crotonaldehyde by 29.8% (P=0.006). In contrast, PEITC had no effect on these mercapturic acids in smokers possessing both genes. PEITC had no effect on the urinary oxidative stress biomarker 8-iso-prostaglandin F2α or the inflammation biomarker prostaglandin E2 metabolite. This trial demonstrates an important role of PEITC in detoxification of environmental carcinogens and toxicants which also occur in cigarette smoke. The selective effect of PEITC on detoxification in subjects lacking both GSTM1 and GSTT1 genes supports the epidemiological findings of stronger protection by dietary isothiocyanates against the development of lung cancer in such individuals.

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Section: Discussionmentioning

confidence: 99%

2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke

Yuan

Murphy

Stepanov

et al. 2016

Cancer Prevention Research

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“…Second, we did not consider whether the genotype distribution in the controls was in HWE for GSTM1 and GSTT1 polymorphism because we cannot calculate the HWE on both genes. The current study also has several advantages over previously published meta-analyses [15–29,31–50] . First, the sample size was larger.…”

Section: Discussionmentioning

confidence: 88%

“…Gao et al [ 18 ] on the combined effects of GSTM1 present/null and GSTT1 present/null polymorphisms with LC risk will be considered as “positive” result in the overall population, Ye et al [ 15 ] on the GSTM1 null genotype with LC risk in all races, Liu et al [ 41 ] on the GSTM1 null genotype with LC risk in Chinese populations, and Xu et al [ 33 ] on the GSTP1 IIe105Val polymorphism with LC risk will be considered as “positive” results because their studies represent the most credible findings. Li et al, [ 28 ] Sengupta et al, [ 50 ] Yang et al, [ 19 ] Yang et al, [ 34 ] Wang et al, [ 40 ] and Feng et al [ 21 ] will be classified as less-credible results (higher heterogeneity, lower statistical power, FPRP > 0.2 and BFDP > 0.8).…”

Section: Resultsmentioning

confidence: 99%

Individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on lung cancer risk

Zhang

Yang

et al. 2021

Medicine

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Thirty-five previous meta-analyses have been reported on the individual glutathione S-transferase M1 ( GSTM1 ) present/null, glutathione S-transferase T1 ( GSTT1 ) present/null, and glutathione S-transferase P1 ( GSTP1 ) IIe105Val polymorphisms with lung cancer (LC) risk. However, they did not appraise the credibility and explore the combined effects between the 3 genes and LC risk. We performed a meta-analysis and re-analysis of systematic previous meta-analyses to solve the above problems. Meta-analyses of Observational Studies in Epidemiology guidelines were used. Moreover, we employed false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria to verify the credibility of current and previous meta-analyses. Significantly increased LC risk was considered as “highly credible” or “positive” for GSTM1 null genotype in Japanese (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.17–1.44, I 2 = 0.0%, statistical power = 0.997, FPRP = 0.008, BFDP = 0.037, and Venice criteria: AAB), for GSTT1 null genotype in Asians (OR = 1.23, 95% CI = 1.12–1.36, I 2 = 49.1%, statistical power = 1.000, FPRP = 0.051, BFDP = 0.771, and Venice criteria: ABB), especially Chinese populations (OR = 1.31, 95% CI = 1.16–1.49, I 2 = 48.9%, Statistical power = 0.980, FPRP = 0.039, BFDP = 0.673, and Venice criteria: ABB), and for GSTP1 IIe105Val polymorphism in Asians (Val vs IIe: OR = 1.28, 95% CI = 1.17–1.42, I 2 = 30.3%, statistical power = 0.999, FPRP = 0.003, BFDP = 0.183, and Venice criteria: ABB). Significantly increased lung adenocarcinoma (AC) risk was also considered as “highly credible” or “positive” in Asians for the GSTM1 (OR = 1.35, 95% CI = 1.22–1.48, I 2 = 25.5%, statistical power = 0.988, FPRP < 0.001, BFDP < 0.001, and Venice criteria: ABB) and GSTT1 (OR = 1.36, 95% CI = 1.17–1.58, I 2 = 30.2%, statistical power = 0.900, FPRP = 0.061, BFDP = 0.727, and Venice criteria: ABB) null genotype. This study indicates that GSTM1 null genotype is associated with increased LC risk in Japanese and lung AC risk in Asians; GSTT1 null genotype is associated with increased LC risk in Chinese, and GSTP1 IIe105Val polymorphism is associated with increased LC risk in Asians.

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“…GSTM1 and GSTT1 null genotype lost enzymatic functional activity, therefore, may increase the risk of lung cancer. To date, a series of previous meta-analysis have only focused on the association between single GSTM1 or GSTT1 gene polymorphism and lung cancer risk [12–14, 63, 64]. However, the combined effect of GSTM1 and GSTT1 has not been reported previously.…”

Section: Discussionmentioning

confidence: 99%

Combined effects of glutathione S-transferase M1 and T1 polymorphisms on risk of lung cancer: evidence from a meta-analysis

Gao¹,

Gao²,

et al. 2017

Oncotarget

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Many studies have reported an association between the glutathione S-transferase M1 null and T1 null polymorphisms and lung cancer risk. However, the combined effects of GSTM1 null and GSTT1 null polymorphisms have not been reported previously. We, therefore, performed a meta-analysis to investigate the combined effects. 40 publications with 44 case–control studies were selected in the meta-analysis, including 13,706 cases and 13,093 controls. Significant association was observed between the combined effects of GSTM1 and GSTT1 polymorphisms and lung cancer risk when all the eligible studies were pooled into the meta-analysis. When we performed subgroup analysis, significantly increased lung cancer risk was observed in Caucasians (− − vs. + +: OR = 1.23, 95% CI: 1.07 to 1.41), Asians (− − vs.− +: OR = 1.24, 95% CI: 1.10 to 1.41; recessive model: OR = 1.45, 95% CI: 1.19 to 1.77; dominant model: OR = 1.53, 95% CI: 1.24 to 1.90), Indians (− − vs. + +: OR = 2.53, 95% CI: 1.61 to 3.98; recessive model: OR = 1.69, 95% CI: 1.07 to 2.67; dominant model: OR = 2.11, 95% CI: 1.36 to 3.28), hospital-based studies, and population-based studies. In summary, this meta-analysis indicates that the combined effects of the GSTM1 and GSTT1 polymorphisms are associated with increased lung cancer risk in Asians, Caucasians, and Indians.

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Association between glutathione S-transferase T1 null genotype and risk of lung cancer: a meta-analysis of 55 studies

Cited by 6 publications

References 54 publications

2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke

2-Phenethyl Isothiocyanate, Glutathione S-transferase M1 and T1 Polymorphisms, and Detoxification of Volatile Organic Carcinogens and Toxicants in Tobacco Smoke

Individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on lung cancer risk

Combined effects of glutathione S-transferase M1 and T1 polymorphisms on risk of lung cancer: evidence from a meta-analysis

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