As previous studies have reported that the GSTM1 null genotype is associated with an increased lung cancer risk, further work is required to determine whether the observed association is true, or whether it arises from bias or confounding factors.
No significant single gene associations between GSTM1, GSTT1 or GSTP1 and early-onset lung cancer were identified in Caucasians, after adjusting for age, sex, pack years and family history of lung cancer.
A gene-gene interaction analysis showed that there was an interaction for individuals with combination of GSTM1 (or GSTT1) null genotype and GSTP1 (AG+GG) mutant genotype for lung cancer risk in Chinese.
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 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.
A common genetic polymorphism divides the population of never smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele).
The aim of present study was to present the results of a case-control study focused on genetic polymorphisms of selected Phase II metabolizing enzymes (GSTM1, T1, and P1) and to investigate the association of these polymorphisms with lung cancer risk in the Slovakian population.
Individuals with the MspI CC genotype showed a two-fold higher risk of lung cancer if they were also null for either GSTM1 or T1 (OR=2.3, 95CI=1.0-5.0 and OR=2.7, 95 CI=1.1-6.9, respectively, compared to other genotype combinations combined).
The selective effect of PEITC on detoxification in subjects lacking both GSTM1 and GSTT1 genes supports the epidemiologic findings of stronger protection by dietary isothiocyanates against the development of lung cancer in such individuals.
In this Chinese cohort, with CYP1A1 valine allele frequency intermediate between Japanese and Caucasian populations, the I462V polymorphism is not related to lung cancer overall, but it might play a role at lower levels of cigarette smoking among subjects with impaired carcinogen detoxification as assessed by the GSTM1-null genotype.
Our results suggest that GSTM1 and GSTT1 polymorphisms may play a role in the development of lung cancer for some histological subtypes and modifies the risk of smoking-related 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.
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.
In a case-control study, it was found that the individual susceptibility to lung cancer risk may be increased by GSTM1 null genotype as well as overexpression of the p53 protein.
Risk modification by CYP1A1 and GSTM1 polymorphisms in the association of environmental tobacco smoke and lung cancer: a case-control study in Japanese nonsmoking women.
An association between the presence of this transversion and the genotype deficient in glutathione S-transferase M1-mediated detoxification has been observed in lung cancer.
Although no significant association between any single genetic variant and lung cancer risk was observed, when genetic variants were analyzed in combination, a significant effect on lung cancer risk was found for the variant allele in a combination of five genes involved in oxidative stress and inflammatory response: GSTM1 (null), MPO (-463A), OGG1 (326Cys), TP53 (72Pro) (alias p53), MMP1 (2G).
Genetic biomarkers such as 2A and GSTM1 polymorphisms in addition to DR70 as screening biomarkers might provide relevant information to identify individuals with a high risk for lung cancer as prevention and protection actions to protect public health.
We observed a stronger association between GSTM1 null genotype and lung cancer among heavy smokers with > or =30 pack-years (OR 4.35, 95% CI 1.16-16.23).