An association of lung cancer susceptibility with an Mspl restriction site polymorphism of the CYP1A1 gene was reported in our previous study. This polymorphism has been subsequently found to be closely linked to another isoleucine-valine (Ile-Val) polymorphism, which resulted in an Ile-Val amino acid replacement in the heme-binding region of P4501A1. We report here that genetic risk for squamous cell carcinoma of the lung was associated with these two polymorphisms of the CYP1A1 gene in terms of genotype frequencies and cigarette-smoking dose and that a more increased risk was observed for the individuals with “susceptible ” genotypes of CYP1A1 combined with a deficient genotype of a u-class glutathione 5-transferase (GST1), which detoxifies the electrophilic metabolites of aromatic hydrocarbon procarcinogens activated by P4501A1. We first compared the total amounts of cigarettes consumed during a lifetime among 85 patients with squamous cell carcinoma of the lung, whose CYP1A1 and GSTl genes were identified. The patients with a susceptible homozygote of each of the Mspl and Ile-Val polymorphisms contracted the carcinoma after smoking fewer cigarettes than those with other genotypes. When the GSTl polymorphism was taken into account, the cumulative cigarette amounts in combined genotyping of the two genes showed distinct differences, resulting in the lowest cigarette dose observed for the patients with a susceptible Mspl or Ile-Val genotype of CYP1A1 combined with a deficient GSTl homozygote. Next, a case-control study revealed that the individuals with the susceptible Mspl or Ile-Val genotype combined with deficient GSTl were at remarkably high risk with an odds ratio of 16.00 or 41.00, respectively (95% confidence interval, 3.76-68.02 or 8.68-193.61, respectively), at a low dose level of cigarette smoking.
|Number of pages||6|
|Publication status||Published - 1993 Aug|
ASJC Scopus subject areas
- Cancer Research