title: Further evidence for the contribution of the RAD51C gene in hereditary breast and ovarian cancer susceptibility.
abstract: RAD51C, a RAD51 paralogue involved in homologous recombination, is a recently established Fanconi anemia and breast cancer predisposing factor. In the initial report, RAD51C mutations were shown to confer a high risk for both breast and ovarian tumors, but most of the replication studies published so far have failed to identify any additional susceptibility alleles. Here, we report a full mutation screening of the RAD51C gene in 147 Finnish familial breast cancer cases and in 232 unselected ovarian cancer cases originating from Finland and Sweden. In addition, in order to resolve whether common RAD51C SNPs are risk factors for breast cancer, we genotyped five tagging single nucleotide polymorphisms, rs12946522, rs304270, rs304283, rs17222691, and rs28363312, all located within the gene, from 993 Finnish breast cancer cases and 871 controls for cancer associated variants. Whereas, none of the studied common SNPs associated with breast cancer susceptibility, mutation analysis revealed two clearly pathogenic alterations. RAD51C c.-13_14del27 was observed in one familial breast cancer case and c.774delT in one unselected ovarian cancer case, thus confirming that RAD51C mutations are implicated in breast and ovarian cancer predisposition, although their overall frequency seems to be low. Independent identification of the very recently reported RAD51C c.774delT mutation in yet another patient originating from Sweden suggests that it might be a recurrent mutation in that population and should be studied further. The reliable estimation of the clinical implications of carrying a defective RAD51C allele still requires the identification of additional mutation positive families.
authors.affiliation: Laboratory of Cancer Genetics, Department of Clinical Genetics and Biocenter Oulu, University of Oulu, Oulu University Hospital, PO Box 5000, 90014 Oulu, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Vuorela
authors.forename: Katri
authors.initials: K
authors.lastname: Pylkäs
authors.forename: Jaana M
authors.initials: JM
authors.lastname: Hartikainen
authors.forename: Karin
authors.initials: K
authors.lastname: Sundfeldt
authors.forename: Annika
authors.initials: A
authors.lastname: Lindblom
authors.forename: Anna
authors.initials: A
authors.lastname: von Wachenfeldt Wäppling
authors.forename: Maria
authors.initials: M
authors.lastname: Haanpää
authors.forename: Ulla
authors.initials: U
authors.lastname: Puistola
authors.forename: Annika
authors.initials: A
authors.lastname: Rosengren
authors.forename: Maarit
authors.initials: M
authors.lastname: Anttila
authors.forename: Veli-Matti
authors.initials: VM
authors.lastname: Kosma
authors.forename: Arto
authors.initials: A
authors.lastname: Mannermaa
authors.forename: Robert
authors.initials: R
authors.lastname: Winqvist
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C448305:RAD51C protein, human