Pooled analysis of the CYP1A1 exon 7 polymorphism and lung cancer (United States).
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.
Le Marchand
Loïc
L
Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA. loic@crch.hawaii.edu
Guo
Chuanfa
C
Benhamou
Simone
S
Bouchardy
Christine
C
Cascorbi
Ingolf
I
Clapper
Margie L
ML
Garte
Seymour
S
Haugen
Aage
A
Ingelman-Sundberg
Magnus
M
Kihara
Masahiro
M
Rannug
Agneta
A
Ryberg
David
D
Stücker
Isabelle
I
Sugimura
Haruhiko
H
Taioli
Emanuela
E
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
D002274:Carcinogens, Environmental; D019363:Cytochrome P-450 CYP1A1