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.
The results showed a 2.4-fold (CI = 1.31-4.41) increased risk of lung cancer in GSTT1 null-genotype carriers but no significant effects of the polymorphisms in GSTM1, GSTM3, GSTP1-105 or GSTP1-114.
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).
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 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.
We studied the potential role of GSTM3 and GSTP1 gene polymorphisms either separately, or in combination with GSTM1 and GSTT1 gene polymorphisms, in susceptibility to lung cancer using peripheral blood DNA from 150 lung cancer patients and 172 control individuals, all regular smokers.
To evaluate the role of the genetic polymorphisms of CYP2E1, GSTM1 and GSTT1, and their interaction with smoking in lung cancer development in Korean males, a hospital-based case-control study was conducted.
In 2141 cases and 2168 controls, weekly consumption of cruciferous vegetables protected against lung cancer in those who were GSTM1 null (odds ratio=0.67, 95% CI 0.49-0.91), GSTT1 null (0.63, 0.37-1.07), or both (0.28, 0.11-0.67).
Overall, there was no significant association between single or combinations of genotypes at GSTM1, GSTT1 or GSTP1 and lung cancer risk after adjustment for age, race, sex and household ETS exposure in years.
'deletion polymorphism (del1) (OR = 1.39, 95% CI = 1.03-1.87, P = 0.027) in GSTT1', 'deletion polymorphism (del2) (OR = 1.30, 95% CI = 1.01-1.67, P = 0.038) in GSTM1' and 'rs1048943 (OR = 1.98, 95% CI = 1.27-3.10, P = 0.002) in CYP1A1' to be associated with lung cancer.
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).
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.
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.
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.
Several case-control studies have found associations of the homozygous null deletions in GSTM1 and GSTT1 with increasing the risk of colorectal and lung cancer.
From our study of 54 lung cancer patients and 50 matched controls, we observed that a combination of several versions of 'unfavorable' metabolizing genes (CYP2D6, CYP2E1, GSTM1 and GSTT1) is strongly associated with lung cancer.
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.