{"entity":{"id":"paper-shimelis-tnbc-risk-genes-jnci-2018","kind":"paper","name":"Triple-negative breast cancer risk genes identified by multigene hereditary cancer panel testing","aka":[],"tldr":"Panel testing of 10,901 women with triple-negative breast cancer pinned down which inherited genes raise the risk of this particular subtype: BARD1, BRCA1, BRCA2, PALB2 and RAD51D carry high risk, and BRIP1, RAD51C and TP53 moderate risk.","summary":"Multigene panel testing for 21 genes in 8,753 TNBC patients by a clinical laboratory and 17 genes in 2,148 patients from the Triple Negative Breast Cancer Consortium was compared with reference controls. Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2 and RAD51D were associated with high risk of TNBC (odds ratio above 5.0) and more than 20% lifetime breast cancer risk among Caucasians; BRIP1, RAD51C and TP53 with moderate risk (odds ratio above 2). Similar trends were observed in the African American population. Pathogenic variants in these genes were detected in 12.0% of participants (3.7% outside BRCA1/2).","asOf":"2026-09-24","links":[{"label":"Shimelis et al., JNCI 2018: TNBC risk genes from panel testing of 10,901 patients","url":"https://doi.org/10.1093/jnci/djy106"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/30099541/"}],"tags":[],"related":[],"cancers":["tnbc"],"sections":[],"technologies":["germline-testing"],"targets":["brca","palb2","bard1","rad51c","rad51d","tp53"],"drugs":[],"companies":[],"institutions":["mayo-clinic"],"pathways":[],"terms":["gbrca-mutation","vus"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["jnci"],"dependsOn":[],"notes":[],"journal":"JNCI: Journal of the National Cancer Institute","year":2018,"doi":"10.1093/jnci/djy106","pmid":"30099541","authors":"Shimelis H, LaDuca H, Hu C, et al.","paperType":"observational","findings":["High-risk TNBC genes: BARD1, BRCA1, BRCA2, PALB2, RAD51D (OR above 5).","Moderate-risk: BRIP1, RAD51C, TP53 (OR above 2).","12.0% of TNBC patients carried a pathogenic variant in these genes, 3.7% outside BRCA1/2."],"whatItMeans":"It defines the gene list a TNBC germline panel should report on and shows the same genes apply in African American women, the population with the highest TNBC incidence.","caveats":["Clinical laboratory referrals are enriched for family history.","Risk estimates outside BRCA1/2 rest on small carrier counts."],"changedPractice":false,"participants":10901},"route":"/key-papers/paper-shimelis-tnbc-risk-genes-jnci-2018/","neighbours":{"cancer":[{"id":"tnbc","kind":"cancer","name":"Triple-negative breast cancer (TNBC)","route":"/cancers/tnbc/"}],"technology":[{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"}],"target":[{"id":"bard1","kind":"target","name":"BARD1","route":"/targets/bard1/"},{"id":"brca","kind":"target","name":"BRCA1 / BRCA2 (HRD)","route":"/targets/brca/"},{"id":"palb2","kind":"target","name":"PALB2","route":"/targets/palb2/"},{"id":"rad51c","kind":"target","name":"RAD51C","route":"/targets/rad51c/"},{"id":"rad51d","kind":"target","name":"RAD51D","route":"/targets/rad51d/"},{"id":"tp53","kind":"target","name":"TP53","route":"/targets/tp53/"}],"institution":[{"id":"mayo-clinic","kind":"institution","name":"Mayo Clinic","route":"/institutions/mayo-clinic/"}],"term":[{"id":"gbrca-mutation","kind":"term","name":"Germline BRCA mutation (gBRCA)","route":"/terms/gbrca-mutation/"},{"id":"vus","kind":"term","name":"Variant of uncertain significance (VUS)","route":"/terms/vus/"}],"journal":[{"id":"jnci","kind":"journal","name":"JNCI: Journal of the National Cancer Institute","route":"/journals/jnci/"}]}}