title: Role of CYP1A2 polymorphisms on lung cancer risk in a prospective study.
abstract: Cytochrome P4501A2 (CYP1A2) is a key enzyme for lung carcinogen activation and lung inflammation. We studied the interactions of the CYP1A2 functional variants -3860G/A(rs2069514),-2467T/delT(rs3569413),-163C/A(rs762551)] with occupational/environmental carcinogenic exposures in the development of lung cancer in a case-control study nested in the Danish prospective cohort "Diet, Cancer and Health." At enrollment (1993-1997), blood samples for genotype analyses and information on lifestyle were collected 5 (mean value) years before the onset of the disease. The study population included 425 lung cancer cases and 786 subcohort members, who were gender- and age-matched. We found that -163A carriers were at increased risk of lung cancer (P=0.035) in a multivariate COX regression model, which was adjusted for personal habits (i.e., cumulative smoking, passive smoke at home, alcohol intake, and fruit intake) and occupational exposure. Additionally, the interaction between -2467delT and smoking increases lung cancer risk in males, especially light smokers (<21.5 pack-years, P=0.004). The increased lung cancer risk found in -163C carriers, independent of smoking status, and in -2467delT male smokers, suggests that these variants could influence lung cancer development through different mechanisms (i.e. lung carcinogen activation and lung inflammation).
authors: Occupational Health Section, Department of Cardiological, Thoracic and Vascular Sciences, Università di Padova, Italy. sofia.pavanello@unipd.it
authors: Sofia
authors: S
authors: Pavanello
authors: Ugo
authors: U
authors: Fedeli
authors: Giuseppe
authors: G
authors: Mastrangelo
authors: Federica
authors: F
authors: Rota
authors: Kim
authors: K
authors: Overvad
authors: Ole
authors: O
authors: Raaschou-Nielsen
authors: Anne
authors: A
authors: Tjønneland
authors: Ulla
authors: U
authors: Vogel
mesh_terms: D016022:Case-Control Studies; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012306:Risk; D012907:Smoking / Q000009:adverse effects
chemical_list: C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2