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The variant E233G of the RAD51D gene could be a low‐penetrance allele in high‐risk breast cancer families without BRCA1/2 mutations
Author(s) -
RodríguezLópez Raquel,
Osorio Ana,
Ribas Gloria,
Pollán Marina,
SánchezPulido Luis,
de la Hoya Miguel,
Ruibal Álvaro,
Zamora Pilar,
Arias Jose Ignacio,
Salazar Raquel,
Vega Ana,
Martínez Jose Ignacio,
EstebanCardeñosa Eva,
Alonso Carmen,
Letón Rocío,
Urioste Azcorra Miguel,
Miner Cristina,
Armengod M. Eugenia,
Carracedo Angel,
GonzálezSarmiento Rogelio,
Caldés Trinidad,
Díez Orland,
Benítez Javier
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20169
Subject(s) - penetrance , breast cancer , allele , genetics , cancer , oncology , single nucleotide polymorphism , biology , population , gene , medicine , cancer research , genotype , environmental health , phenotype
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. © 2004 Wiley‐Liss, Inc.