CYP1A1 polymorphisms and lung cancer risk:: a meta-analysis

To examine the risk of lung cancer associated with the MspI-restriction fragment length polymorphism and Exon7-Val polymorphisms of CYP1A1, a meta-analysis of published case-control studies was undertaken using a random effects model. The principal outcome measure was the odds ratio for the risk of lung cancer, using homozygosity of the 'wild-type allele' as the reference group. Fifteen reports detailing the relationship between the lung cancer and the MspI and Ile-Val polymorphisms of CYP1A1 were identified. The odds ratio of lung cancer associated with the MspI combined variant and homozygous genotypes were 1.09 (0.94-1.25) and 1.27 (0.91-1.77), respectively. The odds ratio of lung cancer associated with the Ile-Val combined variant and homozygous genotypes were 1.16 (0.92-1.48) and 1.62 (0.93-2.82), respectively. The hypothesis that the modulation of carcinogen metabolism is under genetic control is a plausible and attractive mechanism for explaining inter-individual susceptibility of lung cancer. However, the results from this analysis provide little support for the role of variation in the CYP1A1 gene defined by either polymorphisms represents as lung cancer risk factor. Additional well-designed studies based on sample sizes commensurate with the detection of small genotypic risks may allow a more definitive conclusion. Pharmacogenetics 10:105-114 (C) 2000 Lippincott Williams & Wilkins.