Role of 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) variation and lung cancer risk in never-smokers

Carcinogenesis. 2010 Feb;31(2):234-8. doi: 10.1093/carcin/bgp287. Epub 2009 Dec 2.

Abstract

Genome-wide association studies have provided evidence that common variation at 5p15.33 (TERT-CLPTM1L), 6p21.33 and 15q25.1 (CHRNA5-CHRNA3) influences lung cancer risk. To examine if variation at any of these loci influences the risk of lung cancer in never-smokers, we compared 5p15.33-TERT (rs2736100), 5p15.33-CLPTM1L (rs4975616), 6p21.33-BAT3 (rs3117582), 15q25.1-CHRNA3 (rs8042374) and 15q25.1-CHRNA3 (rs12914385) genotypes in a series of 239 never-smoker lung cancer cases and 553 never-smoker controls. A statistically significant association between lung cancer risk and 5p15.33 genotypes was found: rs2736100 (odds ratio = 0.78, 95% confidence interval: 0.63-0.97; P = 0.02), rs4975616 (odds ratio = 0.69, 95% confidence interval: 0.55-0.85; P = 7.95 x 10(-4)), primarily for adenocarcinoma. There was no evidence of association between 6p21.33 or 15q25.1 variation and risk of lung cancer. This analysis provides evidence that TERT-CLPTM1L variants may influence the risk of lung cancer outside the context of tobacco smoking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / secondary
  • Chromosomes, Human, Pair 15 / genetics*
  • Chromosomes, Human, Pair 5 / genetics*
  • Chromosomes, Human, Pair 6 / genetics*
  • Cohort Studies
  • Computational Biology
  • Female
  • Genome-Wide Association Study
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Molecular Chaperones / genetics
  • Neoplasm Proteins / genetics
  • Nerve Tissue Proteins / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Receptors, Nicotinic / genetics
  • Risk Factors
  • Smoking / genetics*
  • Survival Rate
  • Telomerase / genetics*
  • Young Adult

Substances

  • BAG6 protein, human
  • CHRNA5 protein, human
  • CLPTM1L protein, human
  • Membrane Proteins
  • Molecular Chaperones
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Receptors, Nicotinic
  • nicotinic receptor subunit alpha3
  • TERT protein, human
  • Telomerase