The most significant risk for LC (OR = 3.2; 95% CI: 0.7-3.8) was found in the association of the homozygous variant of CYP1A1 gene at A2455G base change at Exon 7 (Val/Val) genotype.
The present study was set up to establish the frequencies of the polymorphic genotypes of CYP1A1 and GSTM1 in Sweden, to evaluate a possible increased incidence of the genotypes associated with higher lung cancer risks among Swedish lung cancer patients and to try to make a combined risk estimate for carriers of multiple risk alleles.
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.
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.
Epidemiologic evidence for the association of aryl hydrocarbon hydroxylase and lung cancer is presently problematic because of difficulties in the assay and subsequent confounding factors.
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.
Thus, the apparently greater susceptibility of the CYP1A1-Val462 genotype to lung cancer is probably not related to greater extents of carcinogen bioactivation.
A pertinent combination of multiple "at-risk" genotypes of CYP1A1rs4646903, the GSTM1 deletion polymorphism and ERCC2 rs13181 was at a 5.94-fold (95% CI = 2.77-12.7) increased risk of lung cancer.
Many investigators have reported an association between genetic polymorphisms of cytochromes P-450 CYP2E1, CYP1A1 or glutathione S-transferase Mu (GSTM1) and susceptibility to lung cancer.
Therefore a lung cancer case-control study was set up to investigate the association of three polymorphisms of the CYP1A1 gene (CYP1A1*2A, CYP1A1*2B, CYP1A1*4) and GSTM1*0 genotype with lung cancer risk in Austrian Caucasians.
A combination of susceptible CYP1A1 and HYL1 genotypes was found to be highly associated with lung cancer, especially with SCC (OR 6.76; 95% CI 2.29-19.10).
Recent clinical studies suggest a relationship between high AHH activity and lung cancer associated with cigarette smoking (Kouri, R.E., McKinney, C.E., Slomiany, D.J., Snodgrass, D.R., Wray, N.P., and McLemore, T.L.Cancer Res.42: 5030-5037, 1982).
Logistic regression analysis was performed to assess the association between each of the CYP1A1 polymorphisms and lung cancer, adjusting for the matching variables (age, sex, ethnicity) and other potential risk factors.
The smokers with CYP1A1 Msp1 (wt/vt+vt/vt), CYP1A1 exon7 (Val/Val+Ile /Val), GSTM1 (-), GSTM3 (AB+BB), and GSTT1 (-) genotypes, respectively, are at elevated risk of lung cancer.
The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes).
In addition, as the gene polymorphisms reflected, the polymorphisms of CYP1A1 (-3801T/C and -4889A/G), CYP1A2 (- 163C/A and -2467T/delT), CYP1B1 (-48G/C, -119G/T and -432G/C), CYP2E1 (-1293G/C and -1053 C/T) have been associated with an increased risk of lung cancer.
DNA was obtained from blood samples and we studied by PCR-RFLP the distribution of CYP1A1 *2B (n=248) and *4 (n=222) polymorphisms in healthy controls and 222 lung cancer patients from a Mexican population.
Overall, a significant association between lung cancer and the variants of CYP1A1 MspI was found among smokers (type B and type C combined vs. type A: OR = 1.89, 95% CI = 1.15-3.11, P = 0.000 for heterogeneity), whereas not found among non-smokers.
In summary, our study demonstrated that the MspI variant CYP1A1 genotype is significantly associated with an increased risk of lung cancer among Caucasians with the odds ratio approximately, equivalent to 2 after controlling for important confounding factors.