title: Association of cigarette smoking and CYP1A1 polymorphisms with adenocarcinoma of the lung by grades of differentiation.
abstract: We have previously reported on an association of genetic susceptibility to squamous cell carcinoma of the lung with two polymorphisms of the CYP1A1 gene, an MspI polymorphism and an isoleucine-valine (Ile-Val) polymorphism. We report here that the two CYP1A1 polymorphisms were associated with current or ex-smokers with adenocarcinoma of the lung. We first compared smoking status of the patients by differentiation grades of adenocarcinoma. Proportion of current or ex-smokers and their cigarette consumption was the highest among the poorly differentiated. Second, the two polymorphisms of CYP1A1 were examined among current or ex-smokers with three differentiation grades, and we found that poorly differentiated adenocarcinoma showed significantly high frequencies of genotypes C and Val/Val, which have been found to be 'susceptible' in squamous cell carcinoma of the lung. Third, a case-control study was carried out to estimate the genetic risk for CYP1A1 genotypes to differentiation grades, selecting only current or ex-smokers in patients and controls. Current or ex-smokers with 'susceptible' genotype C or Val/Val were at significant risk, with an odds ratio of 3.25 or 3.22 (95% confidence interval (CI), 1.40-7.56 or 1.00-10.32) for adenocarcinoma as a whole, respectively. The odds ratio increased to 4.51 or 4.09 (95% CI, 1.73-11.78 or 1.12-14.91) for poorly differentiated, while the odds ratios for other differentiated grades were not significant. Finally, a relation of the genetic risk to cigarette dose levels was evaluated.
authors.affiliation: Department of Epidemiology, Saitama Cancer Center Research Institute, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakachi
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: K
authors.initials: K
authors.lastname: Kawajiri
authors.forename: K
authors.initials: K
authors.lastname: Imai
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D019003:Deoxyribonuclease HpaII / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D007532:Isoleucine / Q000235:genetics; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014633:Valine / Q000235:genetics
chemical_list: D007527:Isoenzymes; D007532:Isoleucine; D003577:Cytochrome P-450 Enzyme System; D019003:Deoxyribonuclease HpaII; D014633:Valine