Breast Cancer Research and Treatment

, Volume 112, Issue 1, pp 35–39

The RAD51D E233G variant and breast cancer risk: population-based and clinic-based family studies of Australian women

  • James G. Dowty
  • Felicity Lose
  • Mark A. Jenkins
  • Jiun-Horng Chang
  • XiaoQing Chen
  • Jonathan Beesley
  • Gillian S. Dite
  • Melissa C. Southey
  • Graham B. Byrnes
  • Andrea Tesoriero
  • Graham G. Giles
  • kConFab Investigators
  • Australian Breast Cancer Family Study (ABCFS)
  • John L. Hopper
  • Amanda B. Spurdle
Preclinical Study

DOI: 10.1007/s10549-007-9832-0

Cite this article as:
Dowty, J.G., Lose, F., Jenkins, M.A. et al. Breast Cancer Res Treat (2008) 112: 35. doi:10.1007/s10549-007-9832-0

Abstract

RAD51D is a homolog of the RAD51 protein, which is known to be an important component of the DNA repair pathway. A rare missense variant in the RAD51D gene, E233G (c.A > G), has been reported to be more prevalent in breast cancer cases from specific multiple-case breast cancer families, with an odds ratio of 2.6 (95% confidence interval (CI): 1.12–6.03). We assessed whether this variant was associated with breast cancer risk using two studies: a population-based case–control-family study based on 1,110 cases and 629 controls, and a clinic-based study based on 390 cases from multiple-case breast cancer families. We conducted case–control analyses and modified segregation analyses of carrier families. The carrier frequencies (95% CI) of the RAD51D variant were 4.1% (2.4–6.6) for clinic-based cases, 3.9% (2.8–5.2) for population-based cases, and 3.7% (2.3–5.4) for population-based controls, and were not significantly higher in case groups than controls (P = 0.7 and P = 0.8, respectively). After genotyping the relatives of cases who carried the variant, modified segregation analyses of these families were conducted, and the estimated hazard ratio for breast cancer corresponding to the E233G variant was 1.30 (95% CI: 0.66–2.58; P = 0.4) for familial breast cancer families and 1.28 (95% CI: 0.47–3.43; P = 0.6) for families unselected for family history. Therefore, despite being well powered to detect moderate risks, no evidence for an association between the E233G variant and breast cancer risk was observed in any setting. Larger studies would be required to determine if this variant is associated with a smaller risk of breast cancer.

Keywords

Breast cancer RAD51D Regressive logistic model Segregation analysis 

Copyright information

© Springer Science+Business Media, LLC. 2007

Authors and Affiliations

  • James G. Dowty
    • 1
  • Felicity Lose
    • 2
    • 3
  • Mark A. Jenkins
    • 1
  • Jiun-Horng Chang
    • 1
  • XiaoQing Chen
    • 2
  • Jonathan Beesley
    • 2
  • Gillian S. Dite
    • 1
  • Melissa C. Southey
    • 4
  • Graham B. Byrnes
    • 1
  • Andrea Tesoriero
    • 4
  • Graham G. Giles
    • 5
  • kConFab Investigators
    • 6
  • Australian Breast Cancer Family Study (ABCFS)
    • 7
  • John L. Hopper
    • 1
  • Amanda B. Spurdle
    • 2
  1. 1.Centre for Molecular, Environmental, Genetic and Analytic EpidemiologyUniversity of MelbourneVictoriaAustralia
  2. 2.Cancer and Cell Biology DivisionQueensland Institute of Medical ResearchBrisbaneAustralia
  3. 3.School of Medicine, Central Clinical DivisionRoyal Brisbane HospitalBrisbaneAustralia
  4. 4.Department of PathologyUniversity of MelbourneVictoriaAustralia
  5. 5.Cancer Council of VictoriaVictoriaAustralia
  6. 6.Peter MacCallum Cancer CentreEast MelbourneAustralia
  7. 7.University of MelbourneMelbourneAustralia

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