Although the interrogated mutation was not prevalent in case-control association study, a comprehensive mutational analysis of the ATM gene revealed 1.78% prevalence of mutations in the ATM gene in HBOC and 1.94% in breast cancer-only BRCAX families in Spanish population, where data about ATM mutations were very limited.
The main aim of this study was to screen epigenetic modifier genes and known breast cancer driver genes for germline mutations in non-BRCA1/2 (BRCAx) breast cancer families in order to identify novel susceptibility genes of moderate-high penetrance.
The likely benign variant p.Val22Met occurred less frequently in patients from the incident BC (p=0.03) and BRCAx groups (p=0.11), respectively, as compared to the controls.
We have defined a group of BRCAX families with short telomeres, suggesting that telomere maintenance genes might be susceptibility genes for breast cancer.
No CHEK2*1100delC mutations were detected in any of the 102 individuals, including 51 women diagnosed with breast cancer at an early age (<45 years), 8 women with bilateral breast cancer, 3 men with breast cancer, and 8 women with ovarian cancer.
Despite significant efforts, BRCA3could not be identified, but several reports have recently been published on genes involved in DNA repair and single nucleotide polymorphisms (SNPs) associated with an increased breast cancer risk.
No "BRCA3" gene has been found to account for the non-BRCA1/BRCA2 breast cancer (BRCAx) families, and BRCAx tumors are increasingly believed to originate from multiple distinct genetic events.
These non-BRCA1/2 breast cancer families (termed BRCAx families) comprise a histopathologically heterogeneous group, further supporting their origin from multiple genetic events.
We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations.No evidence of linkage was found.
Our findings considerably strengthen the evidence for a third breast cancer susceptibility locus (BRCA3) mapping to the short arm of human chromosome 8.