The variant E233G of the RAD51D gene could be a low-penetrance allele in high-risk breast cancer families without BRCA1/2 mutations.
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.
Rodríguez-López
Raquel
R
Department of Human Genetics, Spanish National Cancer Centre, C/Melchior Fernández Almagro 3, 28029 Madrid, Spain. rrodriguez@cnio.es
Osorio
Ana
A
Ribas
Gloria
G
Pollán
Marina
M
Sánchez-Pulido
Luis
L
de la Hoya
Miguel
M
Ruibal
Alvaro
A
Zamora
Pilar
P
Arias
Jose Ignacio
JI
Salazar
Raquel
R
Vega
Ana
A
Martínez
Jose Ignacio
JI
Esteban-Cardeñosa
Eva
E
Alonso
Carmen
C
Letón
Rocío
R
Urioste Azcorra
Miguel
M
Miner
Cristina
C
Armengod
M Eugenia
ME
Carracedo
Angel
A
González-Sarmiento
Rogelio
R
Caldés
Trinidad
T
Díez
Orland
O
Benítez
Javier
J
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
D004268:DNA-Binding Proteins; C112629:RAD51D protein, human