Combinations of cytochrome P-450 genotypes and risk of early-onset lung cancer in Caucasians and African Americans: A population-based study

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2007-03, Vol.55 (3), p.255-262
• Main Authors: Cote, M.L, Wenzlaff, A.S, Bock, C.H, Land, S.J, Santer, S.K, Schwartz, D.R, Schwartz, A.G
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - ethnology; Adenocarcinoma - genetics; Adult; African Americans; African Americans - genetics; Amino Acids, Branched-Chain - genetics; Aryl Hydrocarbon Hydroxylases - genetics; Biological and medical sciences; Case-Control Studies; Caucasians; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP1B1; Cytochrome p-450 polymorphisms; European Continental Ancestry Group - genetics; Exons; Female; Genotype; Hematology, Oncology and Palliative Medicine; Humans; Lung cancer; Lung Neoplasms - ethnology; Lung Neoplasms - genetics; Male; Medical sciences; Pneumology; Polymorphism, Genetic; Pulmonary/Respiratory; Smoking; Smoking - ethnology; Tobacco, tobacco smoking; Toxicology; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2006.11.002

Summary Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found in tobacco smoke. To investigate the potential role these polymorphisms have as modulators of early-onset lung cancer risk, a population-based case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 383 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 449 age, race and sex-matched controls ascertained through random digit dialing. Genotype frequencies varied significantly by race for CYP1A1 Ile 462 Val and CYP1B1 Leu 432 Val genotypes, so all analyses were stratified by race. No association was seen between lung cancer risk and polymorphisms in CYP1A1 Msp1 or CYP1B1 Leu 432 Val for Caucasians or African Americans, after adjusting for age at diagnosis, sex, pack years of smoking and family history of lung cancer. In Caucasians, those with the IIe/Val genotype at CYP1A1 Ile 462 Val locus were at decreased risk of having lung cancer compared to those with the lle/lle genotype, after adjusting for age at diagnosis, sex, pack years of smoking and family history of cancer (OR = 0.41 95% Cl 0.19–0.90). These results were not replicated among the African American population, nor were they modified by amount of smoking.