Research article
Variation in the RAD51 gene and familial breast cancer
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* Corresponding author: Amanda B Spurdle Amanda.Spurdle@qimr.edu.au
1 Cancer and Cell Biology Division, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
2 School of Medicine, Central Clinical Division, University of Queensland, Royal Brisbane Hospital, Brisbane, Queensland, Australia
3 School of Molecular and Microbial Sciences, University of Queensland, Brisbane, Queensland, Australia
4 Westmead Institute for Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead Hospital, Westmead, New South Wales, Australia
Breast Cancer Research 2006, 8:R26 doi:10.1186/bcr1415
Published: 8 June 2006Abstract
Introduction
Human RAD51 is a homologue of the Escherichia coli RecA protein and is known to function in recombinational repair of double-stranded DNA breaks. Mutations in the lower eukaryotic homologues of RAD51 result in a deficiency in the repair of double-stranded DNA breaks. Loss of RAD51 function would therefore be expected to result in an elevated mutation rate, leading to accumulation of DNA damage and, hence, to increased cancer risk. RAD51 interacts directly or indirectly with a number of proteins implicated in breast cancer, such as BRCA1 and BRCA2. Similar to BRCA1 mice, RAD51-/- mice are embryonic lethal. The RAD51 gene region has been shown to exhibit loss of heterozygosity in breast tumours, and deregulated RAD51 expression in breast cancer patients has also been reported. Few studies have investigated the role of coding region variation in the RAD51 gene in familial breast cancer, with only one coding region variant – exon 6 c.449G>A (p.R150Q) – reported to date.
Methods
All nine coding exons of the RAD51 gene were analysed for variation in 46 well-characterised, BRCA1/2-negative breast cancer families using denaturing high-performance liquid chromatography. Genotyping of the exon 6 p.R150Q variant was performed in an additional 66 families. Additionally, lymphoblastoid cell lines from breast cancer patients were subjected to single nucleotide primer extension analysis to assess RAD51 expression.
Results
No coding region variation was found, and all intronic variation detected was either found in unaffected controls or was unlikely to have functional consequences. Single nucleotide primer extension analysis did not reveal any allele-specific changes in RAD51 expression in all lymphoblastoid cell lines tested.
Conclusion
Our study indicates that RAD51 is not a major familial breast cancer predisposition gene.