Polymorphisms in excision repair cross-complementing group 4 (ERCC4) and susceptibility to primary lung cancer in a Chinese Han population

Lung Cancer. 2008 Jun;60(3):332-9. doi: 10.1016/j.lungcan.2007.10.023. Epub 2008 Feb 20.


ERCC4/XPF protein plays an important role in the nucleotide excision repair (NER) pathway, and deficiencies in the gene encoding it can lead to a repair-deficiency syndrome, xeroderma pigmentosum group F (XP-F). Common variants on this gene are assumed to be foreboding markers for lung cancer, and 4 selected SNPs in the ERCC4 gene were genotyped in a multi-center case-control study involving 1010 lung cancer patients and 1011 cancer-free controls in a Chinese Han population to test the hypothesis. A significant association to decreased risk of lung cancer was observed in major allele C of rs3136038 carriers (adjusted OR=0.57, 95% CI=0.39-0.84 for CT; adjusted OR=0.75, 95% CI=0.52-1.10 for CC; adjusted OR=0.68, 95% CI=0.46-0.99 for CT+CC, compared with genotype TT), and additionally, referenced with homozygote TT, the heterozygous genotype CT showed a distinct protective effect in younger subjects (adjusted OR=0.47, 95% CI=0.26-0.86), in males (adjusted OR=0.59, 95% CI=0.37-0.93), in non-smokers (adjusted OR=0.38, 95% CI=0.20-0.72), in subjects without family history of cancer (adjusted OR=0.52, 95% CI=0.34-0.80) and in adenocarcinomas patients (adjusted OR=0.51, 95% CI=0.31-0.84). Our finding indicated, for the first time, the polymorphism rs3136038 on the promotor region of ERCC4 may contribute to the etiology of lung cancer. Further functional studies on this locus and/or other genetic variants in highly linkage disequilibrium with it are warranted to elucidate the underlying molecular mechanisms of the association.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / ethnology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Asian Continental Ancestry Group*
  • Carcinoma, Small Cell / ethnology
  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Small Cell / pathology
  • Carcinoma, Squamous Cell / ethnology
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • DNA Repair / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Linkage Disequilibrium
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Risk Factors
  • Smoking


  • DNA-Binding Proteins
  • xeroderma pigmentosum group F protein