DNA Repair Gene Polymorphisms in Relation to Non-Small Cell Lung Cancer Survival

Cell Physiol Biochem. 2015;36(4):1419-29. doi: 10.1159/000430307.

Abstract

Background: Single nucleotide polymorphisms (SNPs) in the DNA repair genes are suspected to be related to the survival of lung cancer patients due to their possible influence on DNA repair capacity (DRC). However, the study results are inconsistent.

Methods: A follow-up study of 610 non-small cell lung cancer (NSCLC) patients was conducted to investigate genetic polymorphisms associated with the DNA repair genes in relation to NSCLC survival; 6 SNPs were genotyped, including XRCC1 (rs25487 G>A), hOGG1 (rs1052133 C>G), MUTYH (rs3219489 G>C), XPA (rs1800975 G>A), ERCC2 (rs1799793 G>A) and XRCC3 (rs861539 C>T). Kaplan- Meier survival curve and Cox proportional hazards regression analyses were performed. SNP-SNP interaction was also examined using the survival tree analysis.

Results: Advanced disease stage and older age at diagnosis were associated with poor prognosis of NSCLC. Patients with the variant 'G' allele of hOGG1 rs1052133 had poor overall survival compared with those with the homozygous wild 'CC' genotype, especially in female patients, adenocarcinoma histology, early stage, light smokers and without family history of cancer. For never smoking female lung cancer patients, individuals carrying homozygous variant 'AA' genotype of XPA had shorter survival time compared to those with wild 'G' alleles. Furthermore, females carrying homozygous variant XPA and hOGG1 genotypes simultaneously had 2.78-fold increased risk for death. Among all 6 polymorphisms, the homozygous variant 'AA' of XPA carriers had poor prognosis compared to the carriers of wild 'G' alleles of XPA together with other base excision repair (BER) polymorphisms.

Conclusions: Besides disease stage and age, the study found DNA repair gene polymorphisms were associated with lung cancer survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • DNA Glycosylases / genetics
  • DNA Repair*
  • DNA-Binding Proteins / genetics
  • Epistasis, Genetic
  • Female
  • Follow-Up Studies
  • Humans
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Survival Analysis
  • X-ray Repair Cross Complementing Protein 1
  • Xeroderma Pigmentosum Group A Protein / genetics*
  • Xeroderma Pigmentosum Group D Protein / genetics
  • Young Adult

Substances

  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • X-ray repair cross complementing protein 3
  • XPA protein, human
  • XRCC1 protein, human
  • Xeroderma Pigmentosum Group A Protein
  • DNA Glycosylases
  • mutY adenine glycosylase
  • oxoguanine glycosylase 1, human
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human