title: CYP2A6 reduced activity gene variants confer reduction in lung cancer risk in African American smokers--findings from two independent populations.
abstract: We investigated genetic variation in CYP2A6 in relation to lung cancer risk among African American smokers, a high-risk population. Previously, we found that CYP2A6, a nicotine/nitrosamine metabolism gene, was associated with lung cancer risk in European Americans, but smoking habits, lung cancer risk and CYP2A6 gene variants differ significantly between European and African ancestry populations. Herein, African American ever-smokers, drawn from two independent lung cancer case-control studies, were genotyped for reduced activity CYP2A6 alleles and grouped by predicted metabolic activity. Lung cancer risk in the Southern Community Cohort Study (n = 494) was lower among CYP2A6 reduced versus normal metabolizers, as estimated by multivariate conditional logistic regression [odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.26-0.73] and by unconditional logistic regression (OR = 0.62; 95% CI = 0.41-0.94). The association was replicated in an independent study from MD Anderson Cancer Center (n = 407) (OR = 0.64; 95% CI = 0.42-0.98), and pooling the studies yielded an OR of 0.64 (95% CI = 0.48-0.86). Exploratory analyses revealed a significant interaction between CYP2A6 genotype and sex on the risk for lung cancer (Southern Community Cohort Study: P = 0.04; MD Anderson: P = 0.03; Pooled studies: P = 0.002) with a CYP2A6 effect in men only. These findings support a contribution of genetic variation in CYP2A6 to lung cancer risk among African American smokers, particularly men, whereby CYP2A6 genotypes associated with reduced metabolic activity confer a lower risk of developing lung cancer.
authors.affiliation: Department of Pharmacology and Toxicology, The University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Wassenaar
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
authors.forename: Qiuyin
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, TN 37203, USA, Department of Thoracic Surgery Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
authors.forename: Melinda C
authors.initials: MC
authors.lastname: Aldrich
authors.affiliation: Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada, Department of Psychiatry, The University of Toronto, Toronto, Ontario M5T 1R8, Canada.
authors.forename: Joanne
authors.initials: J
authors.lastname: Knight
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA and.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Division of Epidemiology, Vanderbilt University School of Medicine, Nashville, TN 37203, USA, International Epidemiology Institute, Rockville, MD 20850, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Blot
authors.affiliation: Department of Pharmacology and Toxicology, The University of Toronto, Toronto, Ontario M5S 1A8, Canada, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario M5T 1R8, Canada, Department of Psychiatry, The University of Toronto, Toronto, Ontario M5T 1R8, Canada, r.tyndale@utoronto.ca.
authors.forename: Rachel F
authors.initials: RF
authors.lastname: Tyndale
mesh_terms: D000230:Adenocarcinoma / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D001741:Black or African American / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D065637:Cytochrome P-450 CYP2A6 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking; D044465:White People / Q000235:genetics
chemical_list: C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6