The GSTT1 null genotype was also associated with an increased lung cancer risk (OR, 1.49; 95% CI, 1.17-1.89; p=0.001), but no association was observed for the GSTP1 105Val allele.
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.
The polymorphism of CYP1A1*2A or CYP1A1*2B, and the linkage of CYP1A1*2A, CYP1A1*2B, GSTM1 and GSTT1 polymorphisms have been established as susceptible genes or gene-gene interactions of tobacco-related lung cancer.
CYP1A1 rs4646903 (OR = 1.72, 95% CI = 1.25-2.38), rs1048943 (OR = 1.40, 95% CI = 1.02-1.92), the GSTM1 deletion polymorphism (OR = 1.38, 95% CI = 1.01-1.89), GSTP1 rs1695 (OR =1.48, 95% CI = 1.04-2.11), ERCC2 rs13181 (OR = 1.89, 95% CI = 1.28-2.78), and Chinese hamster 1 rs25487 (OR = 1.54, 95% CI = 1.12-2.13) were associated with lung cancer risk whereas the GSTT1 deletion polymorphism and XRCC3 rs861539 were not.
There is a twofold increased risk for lung cancer with the null GSTM1 and wild-type GSTP1 genotypes (P=0.0004); similarly, a fourfold increased risk was observed with the null GSTT1 and wild-type GSTP1 genotypes (P=0.0001).
Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on alpha1-antitrypsin in asbestosis and MPO in lung cancer.
Results showed that CYP1A1 m1 'CC' genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 'AG' gene polymorphisms with 8.8-fold risk and GSTT1 (-/-) genotype demonstrated a twofold risk of disease susceptibility.
The GSTT1*O/*O genotype also appeared to be a possible risk factor in light smokers, whereas, in heavy smokers, this genotype was associated with decreased risk for lung cancer overall (odds ratio 0.36, 95% confidence interval 0.13-0.99).
The present analyses compare the gene gene interactions of the CYP1A1*2A, GSTM1 and GSTT1 polymorphisms from studies on lung cancer conducted in Europe and the USA between 1991 and 2000.Only Caucasians have been included.
No statistically significant effects in the lung cancer risk were observed for the GSTT1 genotypes, but the GSTP1*B/*B genotype posed a 2-fold risk [odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.0-4.1] of this malignancy compared with the GSTP1*A allele containing genotypes; this association was mainly attributable to small cell lung cancer (OR = 3.6, 95% CI 1.3-9.8).
Hence our study-the first to analyse a South Indian population-suggests the importance of combined CYP1A1, GSTM1 and GSTT1 polymorphisms in the development of smoking-induced lung cancer.
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).
In summary, this meta-analysis indicates that the combined effects of the GSTM1 and GSTT1 polymorphisms are associated with increased lung cancer risk in Asians, Caucasians, and Indians.
Because ITCs also serve as a substrate for GSTs, we evaluated dietary intake of ITCs and GSTM1 and GSTT1 genotype information in a lung cancer case-control study.
Data on genetic polymorphisms of glutathione S-transferase Mu 1 (GSTM1) from 68 studies, glutathione S-transferase theta 1 (GSTT1) from 17 studies and GSTM1-GSTT1 from 8 studies in the Chinese population were reanalyzed on their association with lung cancer risk.
Our study showed the GSTT1 null polymorphism to be associated with smoking-induced lung cancer and the GSTM1 null polymorphism to have a link with non-smoking related lung cancer.