Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study

Carcinogenesis. 2011 Aug;32(8):1223-30. doi: 10.1093/carcin/bgr096. Epub 2011 May 27.


Base excision repair (BER) and nucleotide excision repair (NER) pathways repair damaged DNA, and polymorphisms in these genes might affect breast cancer susceptibility. We evaluated associations between seven single-nucleotide polymorphisms in four DNA repair genes (ERCC4 rs1799801, XPC rs2227998, rs2228001, rs2228000, OGG1 rs1052133 and XRCC1 rs25487 and rs25486) and breast cancer risk, examining modification by smoking and alcohol consumption, using data from the Western New York Exposures and Breast Cancer Study. Women aged 35-79 years with incident breast cancer (n = 1170) and age- and race-matched controls (n = 2115) were enrolled. Genotyping was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). No significant associations were observed in premenopausal women. Among postmenopausal women, rs25487 and rs25486 (OR = 1.24; 95% CI 1.01-1.51 and OR = 1.23; 95% CI 1.01-1.49, respectively, for combined heterozygous and homozygous variant compared with reference) were associated with increased risk of breast cancer. Postmenopausal women carrying the variant allele of the synonymous XPC polymorphism (rs2227998) were also at borderline significantly increased risk (OR = 1.24; 95% CI 1.01-1.52, heterozygous variant compared with reference; OR = 1.22; 95% CI 1.01-1.48, for combined heterozygous and homozygous variant compared with reference). There was no evidence of genotype-smoking and genotype-alcohol consumption interactions for pre- and postmenopausal women. These results indicate that some of the variants in BER and NER genes may influence risk of postmenopausal breast cancer.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / genetics*
  • Case-Control Studies
  • DNA Damage
  • DNA Glycosylases / genetics*
  • DNA Repair / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Menopause
  • Middle Aged
  • New York
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Risk Factors
  • Smoking
  • X-ray Repair Cross Complementing Protein 1


  • DNA-Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • xeroderma pigmentosum group F protein
  • XPC protein, human
  • DNA Glycosylases
  • oxoguanine glycosylase 1, human