Sequence variations in the DNA repair gene XPD and risk of lung cancer in a Chinese population

Int J Cancer. 2003 Jul 10;105(5):669-73. doi: 10.1002/ijc.11136.


Variation in DNA repair capacity, which is believed to be largely determined by genetic traits, is linked to risk of certain cancers. The Asp312Asn and Lys751Gln polymorphisms in the xeroderma pigmentosum complementary group D (XPD) gene may alter DNA repair capacity. We thus examined the hypothesis that these 2 XPD polymorphisms are associated with risk of lung cancer via a large hospital-based, case-control study among Chinese. The study subjects consisted of 1,006 patients with primary lung cancer and 1,020 age- and sex-matched population controls. XPD genotypes were determined using PCR-RFLP techniques, and the associations between genotypes and risk of lung cancer were estimated by odds ratios (ORs) and their 95% confidence intervals (CIs) calculated by unconditional logistic regression. Subjects homozygous for the 312Asn/Asn genotype had an increased risk of lung cancer (adjusted OR = 10.33, 95% CI = 1.29-82.50) compared with subjects homozygous for the 312Asp/Asp genotype. The 751Gln/Gln genotype was also associated with increased risk for the cancer compared with the 751Lys/Lys genotype (adjusted OR = 2.71, 95% CI = 1.01-7.24). Stratification analysis revealed that the increased risk was mainly confined to lung squamous cell carcinoma, with the ORs being 20.50 (95% CI = 2.25-179.05) for the 312Asn/Asn genotype and 4.24 (95% CI = 1.34-13.38) for the 751Gln/Gln genotype, respectively. Haplotype analysis with the 2 polymorphisms suggested these polymorphisms might be in linkage disequilibrium with a different causative locus or act together with other functional variants in or close to the XPD locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Amino Acid Substitution
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • China / epidemiology
  • DNA Helicases*
  • DNA Repair / genetics*
  • DNA-Binding Proteins*
  • Ethnic Groups / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Linkage Disequilibrium
  • Logistic Models
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Odds Ratio
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Proteins / genetics*
  • Risk
  • Transcription Factors*
  • Xeroderma Pigmentosum Group D Protein


  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Proteins
  • Transcription Factors
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human