Lung cancer risk in relation to nicotinic acetylcholine receptor, CYP2A6 and CYP1A1 genotypes in the Bangladeshi population.

BACKGROUND

CYP1A1, CYP2A6 and CHRNA5 are biologically plausible genes as risk factors for lung cancer but no studies have been reported in the Bangladeshi population.

METHODS

We conducted this study to determine the prevalence and role of CYP1A1, CYP2A6 and CHRNA5 polymorphisms together with tobacco smoking in the development of lung cancer in Bangladesh. A case-control study was carried out on 106 lung cancer patients and 116 controls to investigate three allelic variants of the CYP1A1 gene-rs4646903, rs1048943 and rs1799814; 2 variants of CYP2A6 (CYP2A61B1, CYP2A64) and 1 variant of CHRNA5 (rs16969968) using Polymerase Chain Reaction Restriction Fragment Length Polymorphism.

RESULTS

Lung cancer risk was estimated as odds ratio (OR) and 95% confidence interval (CI) using unconditional logistic regression models adjusting for age, sex and smoking. A significantly elevated lung cancer risk was associated with heterozygous, mutant and combined heterozygous plus mutant variants of CYP1A1 rs4646903. A significant association was also found for heterozygous and heterozygous plus mutant variants of rs1048943 which was in linkage disequilibrium with rs4646903. The risk of lung cancer was decreased significantly in individuals carrying at least one CYP2A6 deletion (CYP2A6*4) allele. No association with lung cancer risk was found for CHRNA5 rs16969968. When stratified by smoking, the effects of CYP1A1 and CYP2A6 polymorphisms on lung cancer susceptibility were found to be significant only in heavy smokers who had smoked 40 pack years or more (54% of all cases) but no associations were seen for lighter smokers. No association was also found with any polymorphism in the non-smokers in this study.

CONCLUSIONS

Our results indicate that the CYP1A12B allele (rs4646903 and rs1048943) is associated with an increased lung cancer risk and CYP2A64 is associated with a decreased lung cancer risk in the study population.