Detalle de: 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. © 2004 Wiley‐Liss, Inc.