1. The variant E233G of the RAD51D gene could be a low-penetrance allele in high-risk breast cancer families without BRCA1/2 mutations
- Author
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Raquel, Rodríguez-López, Ana, Osorio, Gloria, Ribas, Marina, Pollán, Luis, Sánchez-Pulido, Miguel, de la Hoya, Alvaro, Ruibal, Pilar, Zamora, Jose Ignacio, Arias, Raquel, Salazar, Ana, Vega, Jose Ignacio, Martínez, Eva, Esteban-Cardeñosa, Carmen, Alonso, Rocío, Letón, Miguel, Urioste Azcorra, Cristina, Miner, M Eugenia, Armengod, Angel, Carracedo, Rogelio, González-Sarmiento, Trinidad, Caldés, Orland, Díez, and Javier, Benítez
- Subjects
Ovarian Neoplasms ,Genes, BRCA2 ,Genes, BRCA1 ,Mutation, Missense ,Breast Neoplasms ,Middle Aged ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,DNA-Binding Proteins ,Amino Acid Substitution ,Gene Frequency ,Reference Values ,Mutation ,Humans ,Female ,Age of Onset - 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; p0.021). 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.
- Published
- 2004