Abstract
Several studies in various populations have suggested that non-synonymous BARD1 variants are associated with increased breast cancer risk. Using DHPLC analysis we screened the coding region of BARD1 for variants in 210 probands of breast cancer families including 129 families with no mutations in BRCA1 or BRCA2. These families were ascertained in Australia through the Kathleen Cunningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). Nine coding variants were detected among the kConFab families, including two novel variants (Thr598Ile and Ile692Thr). The frequency of five of these variants were evaluated in 258 non-cancer controls and 401 women with sporadic breast cancer. Three variants (1139del21, G1756C and A2285G) were detected in all three groups at a similar frequency suggesting that these do not represent BRCAX candidates. Two variants (Thr598Ile and Ile692Thr) were not detected in any of the 659 sporadic breast cancer cases and controls and were assessed for segregation with breast cancer in the families of the probands. However, neither variant was identified in any other breast cancer case in either family suggesting that these variants are non-pathogenic polymorphisms. We have found no evidence to support involvement of BARD1 in familial breast cancer risk in the Australian population. In addition, three variants previously reported to be pathogenic in other populations are likely to represent benign polymorphisms and therefore we conclude that BARD1 is unlikely to represent a high-penetrance breast cancer susceptibility gene.
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Acknowledgements
The authors would like to thank Heather Thorne, Danni Surace and Lynda Williams for preparing DNA, the kConFab research nurses and staff of the Familial Cancer Clinics for data collection, kConFab Central Registry staff for supplying data, and the families for their participation. kConFab is supported by the NHMRC Australia, the National Breast Cancer Foundation of Australia and the Cancer Councils of New South Wales, Queensland, South Australia, Victoria and Western Australia. This work was supported by the Victorian Breast Cancer Research Consortium.
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Gorringe, K.L., Choong, D.Y.H., Visvader, J.E. et al. BARD1 variants are not associated with breast cancer risk in Australian familial breast cancer. Breast Cancer Res Treat 111, 505–509 (2008). https://doi.org/10.1007/s10549-007-9799-x
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DOI: https://doi.org/10.1007/s10549-007-9799-x