We evaluated 23 single nucleotide polymorphisms (SNPs) in the five nicotinic receptor related genes (CHRNB3, CHRNA6, and CHRNA5/A3/B4) previously reported to be associated with lung cancer risk and smoking behavior and 14 SNPs in the four 'control' genes (TERT, CLPTM1L, CYP1A1, and TP53), which were not reported in the smoking GWA studies.
If replicated, particularly in prospective studies, these findings would suggest that foods rich in certain flavonoids may protect against certain forms of lung cancer and that decreased bioactivation of carcinogens by inhibition of CYP1A1 should be explored as underlying mechanisms.
Interestingly, positive association between CYP1A1 protein expression and DNA adduct levels was found when CYP1A1 protein expression in lung specimens from lung cancer patients was examined by immunohistochemistry.
The estimated relative risk for lung cancer associated with the CYP1A1 Val/Val allele was 2.68, and was four-fold when cases with small cell lung cancer (SCLC) were considered alone.
Present studies on increased risk of smoking-related lung cancer associated with phenotypic or genotypic variation of the genes encoding for CYP1A1 or CYP2D6 enzymes are summarized.
Since several epidemiological studies have shown an association between the CYP1A1-Val allele and lung cancer, we considered it of importance to evaluate the in vitro kinetic properties of the two CYP1A1 variants after expression of each cDNA in yeast.
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).
The aim of this study was to evaluate the contribution of CYP1A1*2A, CYP1A1*2C, CYP2D6*4, GSTP1, GSTM1, GSTT1 and NAT2 polymorphisms for the susceptibility to LC in a Portuguese population considering their demographic and clinical characteristics.
Thus, the apparently greater susceptibility of the CYP1A1-Val462 genotype to lung cancer is probably not related to greater extents of carcinogen bioactivation.
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.
Through population studies, we have learned that certain CYP1A1 variants, such as Mspl polymorphism, may render the carriers more susceptible to cigarette-induced lung cancer or severe coronary atherosclerosis.
Genetic polymorphisms of NAD(P)H quinone oxidoreductase (NQO1), cytochrome P4501A1 (CYP1A1) and microsomal epoxide hydrolase (HYL1) have been associated with increased lung cancer risk in Asian populations.
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.
These results indicated that the three-order interaction of CYP2A6, CYP1A1, and CYP2D6 polymorphisms might increase genetic susceptibility to lung cancer.
Similarly individuals carrying the mutant CYP1A1*2C genotype and single copy of the variant CYP1A1 Mspl allele, had a relative risk of 2.85 for lung cancer.
The finding of excess CYP1A1 heterozygotes in individuals with p53 mutations after adjustment for smoking suggests that CYP1A1 activation contributes to lung cancer via p53 inactivation.
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.