Collaborator: Mayo Clinic
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Rare BRIP1 missense alleles confer risk for ovarian and breast cancer.
Abstract Germline loss-of-function mutations in BRCA1 interacting protein C-terminal helicase 1 (BRIP1) are associated with ovarian carcinoma and may also contribute to breast cancer risk, particularly among patients who develop disease at an early age. Normal BRIP1 activity is required for DNA interstrand cross-link (ICL) repair and is thus central to the maintenance of genome…
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A clinical guide to hereditary cancer panel testing: evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients
Abstract Purpose Despite the rapid uptake of multigene panel testing (MGPT) for hereditary cancer predisposition, there is limited guidance surrounding indications for testing and genes to include. Methods To inform the clinical approach to hereditary cancer MGPT, we comprehensively evaluated 32 cancer predisposition genes by assessing phenotype-specific pathogenic variant (PV) frequencies, cancer risk associations, and…
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Genetic predisposition to invasive lobular carcinoma
Despite accounting for about 15% of all BCs diagnosed each year, making ILC the second most common histologic subtype after invasive ductal breast cancer (IDC), it is largely underrepresented in genetic studies. Pathogenic alteration frequencies were compared between female ILC and IDC cases, among ~91,000 patients referred for testing, including ~4700 ILC cases Pathogenic alterations…
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Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary Cancer Panel Testing
Abstract Background Germline genetic testing with hereditary cancer gene panels can identify women at increased risk of breast cancer. However, those at increased risk of triple-negative (estrogen receptor–negative, progesterone receptor–negative, human epidermal growth factor receptor–negative) breast cancer (TNBC) cannot be identified because predisposition genes for TNBC, other than BRCA1, have not been established. The aim of…
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Multigene Hereditary Cancer Panels Reveal High-Risk Pancreatic Cancer Susceptibility Genes
Abstract Purpose The relevance of inherited pathogenic mutations in cancer predisposition genes in pancreatic cancer is not well understood. We aimed to assess the characteristics of patients with pancreatic cancer referred for hereditary cancer genetic testing and to estimate the risk of pancreatic cancer associated with mutations in panel-based cancer predisposition genes in this high-risk…
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Polygenic risk score for breast cancer in high-risk women
Speaker: Celine Vachon, MD. PhD (Mayo Clinic) We evaluated a 100-SNP polygenic risk score (PRS) in a high-risk patient population of Caucasian women referred for genetic testing, to determine the extent to which the PRS is predictive of breast cancer. The PRS was significantly higher in cases than controls (mean±SD 1.20±0.88 vs. 0.95±0.69, p<0.0001). The…