Lung cancer susceptibility from GSTM1 deletion and air pollution with smoking status: a meta-prediction of worldwide populations

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.

Profiling the Mutational Landscape in Known Driver Genes and Novel Genes in African American Non–Small Cell Lung Cancer Patients

“…GSTM1 has been studied as a lung cancer susceptibility gene due to its involvement in the detoxification of tobacco smoke. Germline variants have been associated with lung cancer risk in numerous populations (33). Molecular studies also report enhanced platinum sensitivity in lung cancer cell lines when targeting GSTM1 with analogue inhibitors suggesting a role in multidrug resistance pathways (34).…”

Association of oxidative stress, programmed cell death, GSTM1 gene polymorphisms, smoking and the risk of lung carcinogenesis: A two-step Mendelian randomization study

“…Our findings align with the theoretical perspectives on smoking, programmed cell death, and the GSTM1 gene’s role in lung carcinogenesis. The GSTM1 gene detoxifies metabolites of environmental carcinogens like tobacco smoke ( Kabesch et al, 2004 ; Reuter et al, 2010 ; Zhu et al, 2013 ; Yang et al, 2015 ; Adibhesami et al, 2018 ; Yu et al, 2018 ; Arfin, 2021 ; Zhang et al, 2022 ). Its deletion or inadequacy increases susceptibility to lung cancer.…”

“…The Glutathione S Transferase mu 1 (GSTM1) gene has been linked with lung cancer risk, as it plays a role in toxicity and detoxification ( Zhang et al, 2022 ). Deleting this gene has increased the risk of lung cancer ( Yu et al, 2018 ). Thus, smoking and GSTM1 play significant health roles.…”

Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention—results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial

“…Meta-analyses of epidemiological studies have associated the GSTM1 null genotype with enhanced risk of prostate cancer (28, 29) and cancer at other sites (30–32), and several epidemiological studies have reported that the beneficial effect of diets rich in cruciferous vegetables in reducing cancer risk is modified by GSTM1 genotype (33–37). Experimental human dietary intake studies with biological markers have reported greater effect of isothiocyanate intake with GSTM1 null individuals than those with 1 or 2 GSTM1 alleles (38, 39).…”