title: Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States).
abstract: OBJECTIVE
  Cytochrome P450 1A1 plays a major role in the bioactivation of a number of tobacco procarcinogens. Much interest has focused on a polymorphism in exon 7 of the CYP1A1 gene which has been associated with a more inducible form of the enzyme. However, past results of its association with lung cancer have been inconsistent, especially in Caucasians. We carried out a pooled analysis of the data submitted to the Genetic Susceptibility to Environmental Carcinogens (GSEC) database to further investigate this association and, especially, to examine the modifying effects of smoking status and race.
  
  
  METHODS
  The data set used in this analysis included 11 studies and a total of 1950 cases and 2617 controls. Both fixed- and random-effects, meta-analysis models were used to investigate heterogeneity among studies. Because no clear heterogeneity was found, a pooled analysis was conducted using unconditional logistic regression.
  
  
  RESULTS
  The pooled odds ratio for subjects heterozygous and homozygous for the exon 7 polymorphism was 1.15 (95% confidence interval: 0.95-1.39) and 1.54 (95% CI: 0.97-1.46), respectively (p for gene-dosage effect: 0.03). This association was stronger for squamous cell carcinoma (SCC) than adenocarcinoma, and appeared to be stronger in Caucasians than Asians (p for interaction: 0.03). Statistically significant interactions were also detected for smoking status and sex, with the effect of the polymorphism being stronger in never-smokers and in females.
  
  
  CONCLUSIONS
  The present data suggest that the CYP1A1 exon 7 polymorphism may confer an increased risk of lung cancer, particularly of SCC, and especially in never-smokers and in women. These interactions need to be confirmed when additional studies are available for pooling.
authors.affiliation: Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA. loic@crch.hawaii.edu
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Chuanfa
authors.initials: C
authors.lastname: Guo
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.forename: Christine
authors.initials: C
authors.lastname: Bouchardy
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
authors.forename: Margie L
authors.initials: ML
authors.lastname: Clapper
authors.forename: Seymour
authors.initials: S
authors.lastname: Garte
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kihara
authors.forename: Agneta
authors.initials: A
authors.lastname: Rannug
authors.forename: David
authors.initials: D
authors.lastname: Ryberg
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stücker
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics*; D000368:Aged; D002274:Carcinogens, Environmental / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D044469:Racial Groups / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D014481:United States / Q000453:epidemiology
chemical_list: D002274:Carcinogens, Environmental; D019363:Cytochrome P-450 CYP1A1