CYP2A6 reduced activity gene variants confer reduction in lung cancer risk in African American smokers--findings from two independent populations

Carcinogenesis. 2015 Jan;36(1):99-103. doi: 10.1093/carcin/bgu235. Epub 2014 Nov 21.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / ethnology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • African Americans / genetics*
  • Carcinoma, Squamous Cell / ethnology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • Cytochrome P-450 CYP2A6 / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Prognosis
  • Prospective Studies
  • Risk Factors
  • Smoking*

Substances

  • CYP2A6 protein, human
  • Cytochrome P-450 CYP2A6