Abstract

Glutathione S transferase mu 1 (GSTM1) gene has been associated with lung cancer (LC) risk, for GSTM1 enzyme playing a vital role in detoxification pathway and protective against toxic insults. The major objective of this study was to investigate GSTM1 deletion pattern and its association with LC in the world’s population by using meta-prediction techniques. The secondary objective was to examine the effects of air pollution, smoking status, and other factors for gene-environment interactions with GSTM1 deletion and LC risk. We completed a comprehensive search to yield a total of 170 studies (40,296 cases and 48,346 controls) published from 1999 to 2017 for meta-analyses. The results revealed that GSTM1 deletion type was associated with increased risk of LC, while GSTM1 present type provided protective effect for all populations combined worldwide. Subgroup analysis on the rank order of risks from highest to lowest, among racial–ethnic groups, were Chinese, South East Asian, other North Asian, European, and finally American. Additional predictive analyses presented that air pollution played a significant role with increased risks of GSTM1 deletion and LC susceptibility, and the risks increased for smokers with higher levels of air pollution. Based on the findings of meta-predictive analysis, increased air pollution levels and smoking status presented additive effects to the LC risk susceptibilities and GSTM1 gene polymorphisms, for gene-environment interactions. Future studies are needed to examine gene-environment interactions for GSTM1 interacting with environmental factors and dietary interventions to mitigate the toxic effects, for LC prevention.

Highlights

  • Lung cancer (LC) accounts for the second most commonly diagnosed cancer among adults and 25% of all cancer deaths, with delayed diagnosis at a late stage being associated with poor prognosis [1,2,3,4]

  • Glutathione S transferase mu 1 (GSTM1) gene has been associated with lung cancer (LC) risk, for GSTM1 enzyme playing a vital role in detoxification pathway and protective against toxic insults

  • Glutathione S transferase mu 1 (GSTM1) gene has been associated with LC risk, with GSTM1 enzyme playing a vital role in detoxification pathway and protective effect against toxic insults [2, 5,6,7]

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Summary

Introduction

Lung cancer (LC) accounts for the second most commonly diagnosed cancer among adults and 25% of all cancer deaths, with delayed diagnosis at a late stage being associated with poor prognosis [1,2,3,4]. Glutathione S transferase mu 1 (GSTM1) gene has been associated with LC risk, with GSTM1 enzyme playing a vital role in detoxification pathway and protective effect against toxic insults [2, 5,6,7]. GSTM1 is one of phase II detoxification enzymes that detoxify electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins, and byproducts of oxidative stress by conjugation with glutathione (GSH). A deletion of GSTM1 or null mutation deactivates the enzymes, which results in the loss of function within the detoxification pathway [2,3,4]. GSTM1 null genotype has been associated www.oncotarget.com with increased risk of many cancers [8], and increased environmental toxins and carcinogens further increase the susceptibility of LC [2, 4, 5, 7, 12]

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