CYP1A1 Polymorphisms and Risk of Lung Cancer in the Ethnic Kashmiri Population

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 three polymorphisms on lung cancer in ethnic Kashmiris, genotyping 109 lung cancer cases and 163 healthy controls by PCR-RFLP methods. While no polymorphic alleles in CYP1A1m4 (exon 7 thr to asn) site were detected in our population, the allele frequency of CYP1A1m1 (Msp1) and CYP1A1m2 (exon 7 ile to val) were 30.1 and 26.6 in controls and 44.5 and 38.9 in cases. The CYP1A1m1 and CYP1A1m2 variants were significantly associated with lung cancer susceptibility (ORs; 2.65, CI 95% = 1.562-4.49 and 2.24, CI 95%=1.35-3.73). This risk was prominent in case of SCC compared with AC or other types of lung cancer. Stratified analysis showed a multiplicative interaction between tobacco smoking and variant CYP1A1m1 genotype on the risk of SCC. The ORs of SCC for non-smokers were 2.08 and 3.15 for smokers. When stratified by pack years, effect was stronger in the heaviest smokers (ORs=6.00,95% CI=1.672-21.532). The interaction between tobacco smoking and variant CYP1A1m2 genotype followed similar pattern. Our findings thus support the conclusion that CYP1A1m1 and m2 polymorphisms are associated with the smoking related lung cancer risk in Kashmiri population.