Preclinical Study

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. DowtyAffiliated withCentre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne
  • , Felicity LoseAffiliated withCancer and Cell Biology Division, Queensland Institute of Medical ResearchSchool of Medicine, Central Clinical Division, Royal Brisbane Hospital
  • , Mark A. JenkinsAffiliated withCentre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne
  • , Jiun-Horng ChangAffiliated withCentre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne
  • , XiaoQing ChenAffiliated withCancer and Cell Biology Division, Queensland Institute of Medical Research
  • , Jonathan BeesleyAffiliated withCancer and Cell Biology Division, Queensland Institute of Medical Research
  • , Gillian S. DiteAffiliated withCentre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne
  • , Melissa C. SoutheyAffiliated withDepartment of Pathology, University of Melbourne
  • , Graham B. ByrnesAffiliated withCentre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne
    • , Andrea TesorieroAffiliated withDepartment of Pathology, University of Melbourne
    • , Graham G. GilesAffiliated withCancer Council of Victoria
    • , kConFab InvestigatorsAffiliated withPeter MacCallum Cancer Centre
    • , Australian Breast Cancer Family Study (ABCFS)Affiliated withUniversity of Melbourne
    • , John L. HopperAffiliated withCentre for Molecular, Environmental, Genetic and Analytic Epidemiology, University of Melbourne
    • , Amanda B. SpurdleAffiliated withCancer and Cell Biology Division, Queensland Institute of Medical Research Email author 

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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