Are SNP-Smoking Association Studies Needed in Controls? DNA Repair Gene Polymorphisms and Smoking Intensity

PLoS One. 2015 May 27;10(5):e0129374. doi: 10.1371/journal.pone.0129374. eCollection 2015.

Abstract

Variations in tobacco-related cancers, incidence and prevalence reflect differences in tobacco consumption in addition to genetic factors. Besides, genes related to lung cancer risk could be related to smoking behavior. Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Common problems in genetic association studies, such as presence of gene-by-environment (G x E) correlation in the population, may reduce the validity of these designs. The main purpose of this study was to evaluate the independence assumption for selected SNPs and smoking behaviour in a cohort of 320 healthy Spanish smokers. We found an association between the wild type alleles of XRCC3 Thr241Met or KLC3 Lys751Gln and greater smoking intensity (OR = 12.98, 95% CI = 2.86-58.82 and OR=16.90, 95% CI=2.09-142.8; respectively). Although preliminary, the results of our study provide evidence that genetic variations in DNA-repair genes may influence both smoking habits and the development of lung cancer. Population-specific G x E studies should be carried out when genetic and environmental factors interact to cause the disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • DNA Repair / genetics*
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Lung Neoplasms / genetics
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Smoking / genetics*
  • Tobacco Use Disorder / genetics*

Substances

  • DNA-Binding Proteins
  • X-ray repair cross complementing protein 3

Grants and funding

This study was supported by a grant from Universidad Europea, Madrid (project number 2012/UEM17) and Cátedra Florencio Tejerina-UEM (project number 2010/UEM19). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.