The NAT2 slow genotype, in particular when combined with the GSTM1 null genotype, may confer increased susceptibility to adduct formation, gene mutation, and lung cancer when the smoking dose is low.
The present study demonstrates that the presence of null genotype of GSTM1/GSTT1 taken together with CYP1A1 (Val/Val) genotype increases the susceptibility to LC eightfold in comparison to CYP1A1 (Ile/Ile) and GSTM1/ GSTT1 genotype.
The strongest inverse association of total cruciferous vegetable intake with lung cancer risk was seen among individuals with GSTM1 and GSTT1 double null genotypes (odds ratio, 0.41; 95% CI, 0.26-0.65; P for interaction = 0.01).
The risk of lung and urinary bladder cancers was reported to be increased in individuals who carried high risk genotypes in either cytochrome P450 (CYP)1A1, CYP2E1 or glutathione S-transferase (GST)M1, and the combined genotype of both CYP1A1 and GSTM1 enzymes have an enhanced tendency of risk to lung cancer more significantly.
The association between lack of glutathione S-transferase M1 gene (GSTM1 null genotype) and susceptibility to smoking-related lung cancer has been actively studied, with contradictory results.
In addition, a possible interaction was observed between smoking and GSTM1 genotype in the CA assay, GSTM1 null smokers, earlier reported to have an elevated risk for lung cancer, showing higher CA frequencies than GSTM1 positive smokers.
College smokers (N = 128) read a brochure describing a biomarker for lung cancer (the GSTM1 gene) then reported whether they thought they had the gene (indicating lower lung cancer risk) or were missing the gene (indicating higher lung cancer risk).
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.
Screening for the deletion of the GSTM1 and GSTT1 genes may be useful for assessing individual genetic susceptibility to smoking-related lung cancer and MDS.
Furthermore, individuals possessing combined genotypes of N-acetyltransferase 2 (NAT2) rapid acetylator, GSTP1 mutant and both GSTT1(-) and GSTM1(-) have a remarkably higher lung cancer risk than those carrying combined NAT2 slow acetylator genotype, GSTP1 wild genotype and both GSTT1(+) and GSTM1(+) genotypes.
The role of myeloperoxidase (MPO), and glutathione S-transferase mu and theta (GSTM1 and GSTT1) genetic polymorphisms on lung cancer risk was investigated in 110 Caucasian patients and 119 matched controls.
Our findings suggested that CYP1A1 or GSTM1 variants may significantly modify the associations between level of serum trace metals (Cu, Zn, Se or Cr) and NSCLC, indicating the intriguing pathogenesis of lung cancer.
A pertinent combination of multiple "at-risk" genotypes of CYP1A1 rs4646903, the GSTM1 deletion polymorphism and ERCC2 rs13181 was at a 5.94-fold (95% CI = 2.77-12.7) increased risk of lung cancer.
A synergistic increase in susceptibility to lung cancer was observed when the susceptible genotypes of CYP1A1 were combined with a deficient GSTM1 genotype.
Fasting blood samples were collected for assays of PAH-DNA adducts in circulating mononuclear cells, plasma cotinine and serum levels of vitamin A, beta-carotene, vitamin C and vitamin E. Since genetic deficiency in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) has been associated with increased risk of lung cancer, GSTM1 genotype was also determined.
In this study, the involvement of three polymorphic genes (CYP2E1, GSTM1, and GSTT1) in the development of different histological types of lung cancer was investigated.
The results showed that the frequency of the GSTM1 null genotype was higher in the lung cancer patients compared to the controls [odds ratio (OR), 1.57; 95% confidence interval (CI), 0.99-2.51].
Smokers with homozygous CYP1A1 variant and GSTM1 null had the highest adduct levels and were, as shown in Japanese smokers, most susceptible to lung cancer.
Therefore, in 46 published studies in Chinese populations, we found evidence of an association between the CYP1A1 variant and GSTM1 null genotypes and increased risk of lung cancer.