title: Breast cancer risk is not associated with polymorphic forms of xeroderma pigmentosum genes in a cohort of women from Washington County, Maryland.
abstract: BACKGROUND
  The genes mutated in the cancer-prone syndrome, xeroderma pigmentosum (XP genes), have been well studied both biochemically and mechanistically. These genes are important components of the DNA nucleotide excision repair (NER) pathway, which protects against environmentally-induced cancers. XP genes are also downstream of the hereditary breast cancer syndrome gene, BRCA1, suggesting that XP genes may be important to hereditary forms of breast cancer as well. Although mutated XP genes are rare, polymorphic forms with potential functional deficiencies are common, and could pose a significant cancer risk in the general population.
  
  
  OBJECTIVE
  This study tested the hypothesis that common polymorphic variants of XP genes were associated with the risk of breast cancer among a population of women in Washington County, Maryland.
  
  
  METHODS
  Five single nucleotide polymorphisms (SNPs) among four XP genes (XPC, XPD, XPF and XPG) were genotyped from DNA samples collected at baseline, and then analyzed by conditional logistic regression for association with the incidence of breast cancer. 321 cases were individually matched to 321 controls, by age and menopausal status.
  
  
  RESULTS
  No significant associations were found between breast cancer risk and any of the XP genotypes. Odds ratios for all genotypes ranged from 0.61 to 1.14, and none were statistically significant. Adjustment and stratification for family history of breast cancer did not alter the findings.
  
  
  CONCLUSIONS
  These results suggest that polymorphisms of XP genes are not likely to be significant risk factors for women within the general population. This study did not address, however, risks for subpopulations of women with high exposures to DNA damaging agents.
authors.affiliation: Department of Radiation Medicine, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Road, NW, TRB Room E212, Washington, DC 20057, USA. tjorge01@georgetown.edu
authors.forename: T J
authors.initials: TJ
authors.lastname: Jorgensen
authors.forename: K
authors.initials: K
authors.lastname: Visvanathan
authors.forename: I
authors.initials: I
authors.lastname: Ruczinski
authors.forename: L
authors.initials: L
authors.lastname: Thuita
authors.forename: S
authors.initials: S
authors.lastname: Hoffman
authors.forename: K J
authors.initials: KJ
authors.lastname: Helzlsouer
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D015331:Cohort Studies; D004260:DNA Repair / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008396:Maryland; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014983:Xeroderma Pigmentosum / Q000235:genetics*