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RAD51, XRCC3, and XRCC2 mutation screening in Finnish breast cancer families
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RAD51, XRCC3, and XRCC2 mutation screening in Finnish breast cancer families
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Journal Article
RAD51, XRCC3, and XRCC2 mutation screening in Finnish breast cancer families
2015
Overview
Majority of the known breast cancer susceptibility genes have a role in DNA repair and the most important high-risk genes
BRCA1
and
BRCA2
are specifically involved in the homologous recombination repair (HRR) of DNA double-strand breaks. A central player in HRR is RAD51 that binds DNA at the damage site. The RAD51 paralogs RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3 facilitate the binding of RAD51 to DNA. While germline mutations in
RAD51C
and
RAD51D
are associated with high ovarian cancer risk and
RAD51B
polymorphisms with breast cancer, the contribution of
RAD51, XRCC3,
and
XRCC2
is more unclear. To investigate the role of
RAD51, XRCC3,
and
XRCC2
in breast cancer predisposition and to identify putative recurrent founder mutations in the Finnish population where such mutations have been observed in most of the currently known susceptibility genes, we screened 182 familial Finnish breast or ovarian cancer patients for germline variation in the
RAD51
and
XRCC3
genes and 342 patients for variation in
XRCC2
, with a subset of the patients selected on the basis of decreased RAD51 protein expression on tumors. We also performed haplotype analyses for 1516 breast cancer cases and 1234 controls to assess the common variation in these genes. No pathogenic mutations were detected in any of the genes and the distribution of haplotypes was similar between cases and controls. Our results suggest that
RAD51, XRCC3,
and
XRCC2
do not substantially contribute to breast cancer predisposition in the Finnish population.
Publisher
Springer International Publishing,Springer Nature B.V
