Triple-Negative Breast Cancer Risk Linked to Germline Variants in Several Cancer Genes

NEW YORK (GenomeWeb) – Germline alterations affecting a handful of cancer-associated genes appear to dial up the risk of breast cancer, new research suggests, particularly triple-negative breast cancers (TNBC) that do not express receptors for estrogen, progesterone, or the human epidermal growth factor.

“This study is the first to establish which genes are associated with high lifetime risks of triple-negative breast cancer,” corresponding author Fergus Couch, a laboratory medicine, pathology, and genetics researcher at the Mayo Clinic in Rochester, Minnesota, said in a statement.

Couch and his colleagues searched for suspicious germline mutations in panel sequence data generated for almost 8,800 TNBC cases assessed at the Ambry Genetics clinical testing laboratory, focusing on 21 genes implicated in cancer risk and another 2,148 individuals with TNBC who received panel sequencing across 17 cancer-related genes through a Triple-Negative Breast Cancer Consortium (TNBCC) study.

From these data, the team tracked down risky germline mutations in the BARD1, BRCA1/2, PALB2, and RAD51D genes that were linked to breast cancer — and with an especially high risk of TNBC — in individuals with Caucasian ancestry. Alterations in the BRIP1, RAD51C, and TP53 genes had apparent ties to TNBC as well, albeit at more moderate risk

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