Human Genetics

, 119:376

Polymorphisms in DNA double-strand break repair genes and risk of breast cancer: two population-based studies in USA and Poland, and meta-analyses

  • Montserrat García-Closas
  • Kathleen M. Egan
  • Polly A. Newcomb
  • Louise A. Brinton
  • Linda Titus-Ernstoff
  • Stephen Chanock
  • Robert Welch
  • Jolanta Lissowska
  • Beata Peplonska
  • Neonila Szeszenia-Dabrowska
  • Witold Zatonski
  • Alicja Bardin-Mikolajczak
  • Jeffery P. Struewing
Original Investigation

Abstract

The double-strand break DNA repair pathway has been implicated in breast carcinogenesis. We evaluated the association between 19 polymorphisms in seven genes in this pathway (XRCC2, XRCC3, BRCA2, ZNF350, BRIP1, XRCC4, LIG4) and breast cancer risk in two population-based studies in USA (3,368 cases and 2,880 controls) and Poland (1,995 cases and 2,296 controls). These data suggested weak associations with breast cancer risk for XRCC3 T241M and IVS7-14A>G (pooled odds ratio (95% confidence interval): 1.18 (1.04–1.34) and 0.85 (0.73–0.98) for homozygous variant vs wild-type genotypes, respectively), and for an uncommon variant in ZNF350S472P (1.24 (1.05–1.48)), with no evidence for study heterogeneity. The remaining variants examined had no significant relationships to breast cancer risk. Meta-analyses of studies in Caucasian populations, including ours, provided some support for a weak association for homozygous variants for XRCC3 T241M (1.16 (1.04–1.30); total of 10,979 cases and 10,423 controls) and BRCA2 N372H (1.13 (1.10–1.28); total of 13,032 cases and 13,314 controls), and no support for XRCC2 R188H (1.06 (0.59–1.91); total of 8,394 cases and 8,404 controls). In conclusion, the genetic variants evaluated are unlikely to have a substantial overall association with breast cancer risk; however, weak associations are possible for XRCC3 (T241M and IVS7-14A>G), BRCA2 N372H, and ZNF350 S472P. Evaluation of potential underlying gene–gene interactions or associations in population subgroups will require even larger sample sizes.

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Montserrat García-Closas
    • 1
  • Kathleen M. Egan
    • 2
  • Polly A. Newcomb
    • 3
    • 4
  • Louise A. Brinton
    • 1
  • Linda Titus-Ernstoff
    • 5
  • Stephen Chanock
    • 6
  • Robert Welch
    • 6
  • Jolanta Lissowska
    • 7
  • Beata Peplonska
    • 8
  • Neonila Szeszenia-Dabrowska
    • 8
  • Witold Zatonski
    • 7
  • Alicja Bardin-Mikolajczak
    • 7
  • Jeffery P. Struewing
    • 9
  1. 1.Division of Cancer Epidemiology and GeneticsNational Cancer Institute, National Institutes of Health, Department of Health and Human ServicesRockvilleUSA
  2. 2.Vanderbilt University Medical CenterNashvilleUSA
  3. 3.Fred Hutchinson Cancer Research CenterCancer Prevention Research GroupSeattleUSA
  4. 4.Comprehensive Cancer Center and Department of Population Health SciencesUniversity of WisconsinMadisonUSA
  5. 5.Dartmouth Medical SchoolNorris Cotton Cancer CenterLebanonUSA
  6. 6.Department of Health and Human Services, Core Genotyping Facility, Division of Cancer Epidemiology and GeneticsNational Cancer Institute, National Institutes of HealthGaithersburgUSA
  7. 7.Department of Cancer Epidemiology and PreventionM. Sklodowska-Curie Institute of Oncology and Cancer CenterWarsawPoland
  8. 8.Nofer Institute of Occupational MedicineLodzPoland
  9. 9.Department of Health and Human Services, Laboratory of Population GeneticsNational Cancer Institute, National Institutes of HealthBethesdaUSA

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