CYP2A6 gene deletion reduces susceptibility to lung cancer

CYP2A6 is an enzyme with a high ability to activate a nitrosamine, 4-(methy lnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), to its potent and ultimate ca rcinogen. In the present study, we investigated the relationship between ge netic polymorphism of CYP2A6 and lung cancer risk in a case-control study o f Japanese subjects. Genotyping of the CYP2A6 gene in both healthy voluntee rs and lung cancer patients was conducted. The frequency with which the sub jects carried homozygotes of the CYP2A6 gene deletion-type mutation (deleti on), which causes lack of the enzyme activity, was lower in the lung cancer patients than in the healthy control subjects. The odds ratio (OR) of the group homozygous for the deletion was significantly lower and calculated to be 0.25 (95% CI; 0.08-0.83) when the OR for the population with homozygote s of the CYP2A6 wild-type gene was defined as 1.00, In the allelic-base ana lysis, there was also a significant decrease in the OR for the deletion all ele, These data suggest that deficient CYP2A6 activity due to genetic polym orphism reduces lung cancer risk. (C) 1999 Academic Press.