A consecutive sampling of lung cancer cases was performed in 1999-2000 at the University Hospital of Santiago de Compostela, Spain, and GSTM1 and GSTT1 genes were genotyped.
GSTT1 and GSTM1 null genotypes appeared to play a protective role for lung cancer (odds ratio [OR] = 0.47, 95% confidence interval [95% CI]: 0.24-0.93, p = 0.03) and (OR = 0.52, 95% CI: 0.28-0.96, p = 0.04), but they were not associated with oral and gastric cancers.
The proportion of GSTM1-deficient individuals gradually increased from elderly controls (70/157; 45%) to middle-aged ones (77/140; 55%) to lung cancer sufferers (34/58; 59%), showing the minimal estimates in elderly non-affected smokers (35/81; 43%) and the maximal ones in the affected non-smokers (7/7, 100%).
Results revealed that certain environmental factors may be considered as a risk factor but deletion of GSTM1 and GSTT1 are not associated with the development of lung cancer; however, studies including >500 patient samples is suggested.
The estimated relative risk of the GSTM1 null genotype for lung cancer was 2.58 (95%CI = 1.26-5.30) in smokers with the GSTP1 mutant allele while it was 1.17 (95%CI = 0.77-1.79) in those without, suggesting that mutated GSTM1 and GSTP1 genotypes interact to potentiate the risk of lung cancers in Japanese smokers.
The combined GSTM1 null/GSTP1 Val genotype was associated with lung cancer overall and especially among former smokers, before and after adjusting for adducts (OR for former smokers = 4.21, CI 1.08, 16.41; adjusted OR = 4.68, CI 1.17, 18.71).
These values are significantly higher than those of Caucasians except for the GSTM1 'null' genotype and suggest differences in susceptibility to lung cancer between both populations.
Individuals with the GSTM1-null and/or NAT2-slow genotypes may constitute susceptible groups with increased risk to contract non-operable lung cancer at younger age and lower smoking dose.
This meta-analysis showed that the null GSTM1 may be a potential biomarker for lung cancer risk in Chinese, but further studies with gene-gene and gene-environment interactions are required for definite conclusions.
The behavioural and psychological impact of genetic testing for lung cancer susceptibility was examined among smokers (N = 61) who were randomly allocated to a GSTM1 genetic testing group (with GSTM1-missing or GSTM1-present result) or no-test control group.
The finding of an association between m(7)Gua excretion and lung cancer risk mainly among current smokers and subjects with GSTM1 null genotype supports causality in this respect.
The estimated risk of the GSTM1 null genotype for lung cancer was OR=1.34 (95%-CI: 0.99-1.81) and for the GSTT1 null genotype OR=0.88 (95%-CI: 0.59-1.32).
The results show that the GSTM1 null genotype (GSTM1*0/GSTM1*0) was slightly over represented in the lung cancer patients (frequency of 58%; OR: 1.40, 95% CI: 0.74-2.61, referred to healthy smokers).
Taken together, these findings suggest that Chilean people carrying single or combined GSTM1 and CYP1A1 polymorphisms could be more susceptible to lung cancer induced by environmental pollutants such as polycyclic aromatic hydrocarbons.
Gene deletion at the glutathione S-transferase mu locus (GSTM1) has previously been associated with increased risk for environmentally-induced cancers (e.g. smoking-related lung cancer).
<i>Glutathione S transferase mu 1</i> (<i>GSTM1</i>) 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 risk of lung cancer was increased with the combination of CYP1A1*2B or CYP1A1*4 alleles and the double deletion of both GSTM1 and GSTT1 up to an odds ratio (OR) of 8.25 (95% confidence interval 2.29-29.77) for the combination including CYP1A1*4; among never smokers, the latter combination was associated with an OR of 16.19 (1.90-137).
There were no statistically significant correlations between (i) daily cigarette dose and DNA adduct levels in current smokers, (ii) DNA adduct level and histological type of lung cancer, or (iii) GSTM1 and CYP1A1 MspI genotypes and DNA adduct levels after adjustment for either smoking status or malignancy.
Urinary ITC levels were not associated overall with lower lung cancer risk among non-smoking women, but secondary analyses suggested an interaction between urinary ITC levels, GSTM1 genotype, and lung cancer risk.