Breast Cancer Research and Treatment

, Volume 115, Issue 3, pp 613–622

Genetic variation in DNA repair pathway genes and premenopausal breast cancer risk

  • Jiali Han
  • Christopher Haiman
  • Tianhua Niu
  • Qun Guo
  • David G. Cox
  • Walter C. Willett
  • Susan E. Hankinson
  • David J. Hunter
Epidemiology

DOI: 10.1007/s10549-008-0089-z

Cite this article as:
Han, J., Haiman, C., Niu, T. et al. Breast Cancer Res Treat (2009) 115: 613. doi:10.1007/s10549-008-0089-z

Abstract

Purpose We comprehensively evaluated genetic variants in DNA repair genes with premenopausal breast cancer risk. Methods In this nested case–control study of 239 prospectively ascertained premenopausal breast cancer cases and 477 matched controls within the Nurses’ Health Study II, we evaluated 1,463 genetic variants in 60 candidate genes across five DNA repair pathways, along with DNA polymerases, Fanconi Anemia complementation groups, and other related genes. Results Four variants were associated with breast cancer risk with a significance level of <0.01; two in the XPF gene and two in the XRCC3 gene. An increased risk was found in those harboring a greater number of missense putative risk alleles (a priori defined in an independent study) in the non-homologous end-joining (NHEJ) repair pathway of double-strand breaks (odds ratio (OR) per risk allele, 1.37 (95% confidence interval (CI), 1.03–1.82), P trend, 0.03). Conclusions This study implicates variants of genes in the double-strand break repair pathway in the etiology of premenopausal breast cancer.

Keywords

Polymorphism DNA repair Breast cancer Premenopausal women 

Abbreviations

BER

Base excision repair

CI

Confidence interval

DSB

Double strand break

ER

Estrogen receptor

HR

Homologous recombination

LD

Linkage disequilibrium

MMR

Mismatch repair

NER

Nucleotide excision repair

NHEJ

Non-homologous end-joining

OR

Odds ratio

PR

Progesterone receptor

SNP

Single nucleotide polymorphism

Supplementary material

10549_2008_89_MOESM1_ESM.pdf (91 kb)
MOESM1 (PDF 90 kb)

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Jiali Han
    • 1
    • 2
    • 3
  • Christopher Haiman
    • 4
  • Tianhua Niu
    • 3
    • 5
  • Qun Guo
    • 1
    • 2
  • David G. Cox
    • 3
    • 5
  • Walter C. Willett
    • 1
    • 2
    • 5
    • 6
  • Susan E. Hankinson
    • 1
    • 2
    • 5
  • David J. Hunter
    • 1
    • 2
    • 3
    • 5
    • 6
  1. 1.Channing Laboratory, Department of MedicineBrigham and Women’s HospitalBostonUSA
  2. 2.Channing Laboratory, Department of MedicineHarvard Medical SchoolBostonUSA
  3. 3.Program in Molecular and Genetic EpidemiologyHarvard School of Public HealthBostonUSA
  4. 4.Department of Preventive Medicine, Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA
  5. 5.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  6. 6.Department of NutritionHarvard School of Public HealthBostonUSA

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