title: CYP1A1 T3801 C polymorphism and lung cancer: a pooled analysis of 2451 cases and 3358 controls.
abstract: CYP1A1 is involved in the metabolism of benzopyrene, a suspected lung carcinogen; it is therefore conceivable that genetically determined variations in its activity modify individual susceptibility to lung cancer. The role of the CYP1A1 MspI polymorphism in lung cancer has been widely studied but has not been fully clarified. We have included 2,451 cases and 3,358 controls in a pooled analysis of 22 case-control studies on CYP1A1 and lung cancer risk. We found a clear association between the CYP1A1 homozygous MspI restriction fragment length polymorphism (RFLP) and lung cancer risk in Caucasians (age- and gender-adjusted odds ratio = 2.36; 95% confidence interval 1.16-4.81); other associations were weaker or not statistically significant. The association with the homozygous variant was equally strong for squamous cell carcinomas and adenocarcinomas among Caucasians. We analyzed the risk by duration of smoking: for Caucasian subjects with the MspI RFLP combined variants (homozygotes plus heterozygotes), the increase in the risk of lung cancer was steeper than among the individuals with the homozygous reference allele. Our analysis suggests that Caucasians with homozygous variant CYP1A1 polymorphism have a higher risk of lung cancer. The data were more consistent among Caucasians, with a strong association between the homozygous variant in both squamous cell carcinomas and adenocarcinomas, and a stronger association in men than in women. The analyses were more inconsistent and failed to reach statistical significance in Asians. This observation might be due to design specificities or unknown effect modifiers in the Asian studies.
authors.affiliation: Università degli studi di Torino, Torino, Italy. paolo.vineis@unito.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.forename: Simone
authors.initials: S
authors.lastname: Benhamou
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: Ingolf
authors.initials: I
authors.lastname: Cascorbi
authors.forename: Margie L
authors.initials: ML
authors.lastname: Clapper
authors.forename: Vita
authors.initials: V
authors.lastname: Dolzan
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.forename: Ari
authors.initials: A
authors.lastname: Hirvonen
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kihara
authors.forename: Chikako
authors.initials: C
authors.lastname: Kiyohara
authors.forename: Pierre
authors.initials: P
authors.lastname: Kremers
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Susumu
authors.initials: S
authors.lastname: Ohshima
authors.forename: Roberta
authors.initials: R
authors.lastname: Pastorelli
authors.forename: Agneta
authors.initials: A
authors.lastname: Rannug
authors.forename: Marjorie
authors.initials: M
authors.lastname: Romkes
authors.forename: Bernadette
authors.initials: B
authors.lastname: Schoket
authors.forename: Peter
authors.initials: P
authors.lastname: Shields
authors.forename: Richard C
authors.initials: RC
authors.lastname: Strange
authors.forename: Isabelle
authors.initials: I
authors.lastname: Stucker
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Sugimura
authors.forename: Seymour
authors.initials: S
authors.lastname: Garte
authors.forename: Laura
authors.initials: L
authors.lastname: Gaspari
authors.forename: Emanuela
authors.initials: E
authors.lastname: Taioli
mesh_terms: D000367:Age Factors; D016022:Case-Control Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D044469:Racial Groups / Q000235:genetics; D012307:Risk Factors; D012727:Sex Characteristics; D012907:Smoking; D013997:Time Factors
chemical_list: D019363:Cytochrome P-450 CYP1A1