Genetic variation in cyp1a1 gene towards risk of occurrence of lung carcinoma in north indian population

Abstract

Lung cancer is the most common cause of death throughout the world with cigarette smoking being established as the major etiological factor in lung cancer. The CYP1A1 category of enzymes plays a central role in the metabolic activation of major tobacco carcinogens. Several polymorphisms within the CYP1A1 locus have been identified and have been shown to be associated with lung cancer risk, particularly in Asian populations. Here we focused on the influence of one polymorphism on lung cancer in ethnic North Indian Population, genotyping 84 lung cancer cases and 86 healthy controls by PCR-RFLP methods. Allele frequency of CYP1A1*2A/*2A were 16.66% in cases and 5.81% in controls. The CYP1A1*2A/*2A variant was significantly associated with lung cancer susceptibility (OR=3.818, 95% CI= 1.215-11.650, p-value= 0.014). This risk was prominent in case of SQCC compared with AC or other types of lung cancer (OR=5.25, 95% CI=1.413-19.505, p-value= 0.008). Stratified analysis showed a significant association between tobacco smoking and variant CYP1A1M1 genotype on the risk of SQCC. Among smokers those carrying CYP1A1*2A/*2A genotype had almost five fold increase in lung cancer. Smokers having with CYP1A1*2A/*2A mutant genotype had 7 fold elevated risk of SQCC (OR=7, 95% CI=0.743-65.943, p-value = 0.0614). Our findings thus support the conclusion that CYP1A1*2A/*2A polymorphism is associated with the smoking related lung cancer risk in North Indian population. Also concluding that the CYP1A1*2A mutant allele is an important risk factor of lung cancer especially for SQCC.