title: The variant E233G of the RAD51D gene could be a low-penetrance allele in high-risk breast cancer families without BRCA1/2 mutations.
abstract: Six SNPs have been detected in the DNA repair genes RAD51C and RAD51D, not previously characterized. The novel variant E233G in RAD51D is more highly represented in high-risk, site-specific, familial breast cancer cases that are not associated with the BRCA1/2 genes, with a frequency of 5.74% (n = 174) compared to a control population (n = 567) and another subset of breast cancer patients (n = 765) with a prevalence of around 2% only (comparison to controls, OR = 2.6, 95% CI 1.12-6.03; p < 0.021). We found that the immunohistochemical profile detected in available tumors from these patients differs slightly from those described in non-BRCA1/2 tumors. Finally, the structural prediction of the putative functional consequence of this change indicates that it can diminish protein stability and structure. This suggests a role for E233G as a low-penetrance susceptibility gene in the specific subgroup of high-risk familial breast cancer cases that are not related to BRCA1/2.
authors.affiliation: Department of Human Genetics, Spanish National Cancer Centre, C/Melchior Fernández Almagro 3, 28029 Madrid, Spain. rrodriguez@cnio.es
authors.forename: Raquel
authors.initials: R
authors.lastname: Rodríguez-López
authors.forename: Ana
authors.initials: A
authors.lastname: Osorio
authors.forename: Gloria
authors.initials: G
authors.lastname: Ribas
authors.forename: Marina
authors.initials: M
authors.lastname: Pollán
authors.forename: Luis
authors.initials: L
authors.lastname: Sánchez-Pulido
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Hoya
authors.forename: Alvaro
authors.initials: A
authors.lastname: Ruibal
authors.forename: Pilar
authors.initials: P
authors.lastname: Zamora
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Arias
authors.forename: Raquel
authors.initials: R
authors.lastname: Salazar
authors.forename: Ana
authors.initials: A
authors.lastname: Vega
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Martínez
authors.forename: Eva
authors.initials: E
authors.lastname: Esteban-Cardeñosa
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.forename: Rocío
authors.initials: R
authors.lastname: Letón
authors.forename: Miguel
authors.initials: M
authors.lastname: Urioste Azcorra
authors.forename: Cristina
authors.initials: C
authors.lastname: Miner
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Armengod
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.forename: Rogelio
authors.initials: R
authors.lastname: González-Sarmiento
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.forename: Orland
authors.initials: O
authors.lastname: Díez
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
mesh_terms: D017668:Age of Onset; D019943:Amino Acid Substitution; D001943:Breast Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010051:Ovarian Neoplasms / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values
chemical_list: D004268:DNA-Binding Proteins; C112629:RAD51D protein, human