{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T16:14:10Z","timestamp":1779380050416,"version":"3.53.1"},"reference-count":0,"publisher":"Ethnicity and Disease Inc","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ethn Dis"],"abstract":"<p class=\"Pa7\"><strong>Background: <\/strong>Variants of unknown signifi\u00adcance (VUSs) have been identified in <em>BRCA1 <\/em>and <em>BRCA2 <\/em>and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age.<\/p><p class=\"Pa7\"><strong>Methods: <\/strong>In our study, the spectrum of mu\u00adtations in <em>BRCA1 <\/em>and <em>BRCA2 <\/em>was enumer\u00adated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and\/or with triple negative breast cancer. To improve the characterization of the <em>BRCA1 <\/em>and <em>BRCA2 <\/em>variants, bioinfor\u00admatics tools were utilized to predict the potential function of each of the variants.<\/p><p class=\"Pa7\"><strong>Results: <\/strong>Using next generation sequencing methods and <em>in silico <\/em>analysis of variants, a total of 197 <em>BRCA1 <\/em>and 266 <em>BRCA2 <\/em>vari\u00adants comprising 77 unique variants were identified in 31 patients. Of the 77 unique variants, one (1.3%) was a pathogenic frameshift mutation (rs80359304; <em>BRCA2 <\/em>Met591Ile), 13 (16.9%) were possibly pathogenic, 34 (44.2%) were benign, and 29 (37.7%) were VUSs. Genetic epidemio\u00adlogical approaches were used to determine the association with variant, haplotype, and phenotypes, such as age at diagnosis, family history of cancer and family history of breast cancer. There were 5 BRCA1 SNPs associated with age at diagnosis; rs1799966 (P=.045; Log Additive model), rs16942 (P=.033; Log Additive model), rs1799949 (P=.058; Log Additive model), rs373413425 (P=.040 and .023; Dominant and Log Additive models, respectively) and rs3765640 (P=.033 Log Additive model). Additionally, a haplotype composed of all 5 SNPs was found to be significantly associated with younger age at diagnosis using linear regression modeling (P=.023). Specifically, the haplotype containing all the variant alleles was associated with older age at diagnosis (OR= 5.03 95% CI=.91-9.14).<\/p><p class=\"Pa7\"><strong>Conclusions: <\/strong>Knowing a patient\u2019s BRCA mutation status is important for prevention and treatment decision-making. Improv\u00ading the characterization of mutations will lead to better management, treatment, and BCa prevention efforts in African Ameri\u00adcans who are disproportionately affected with aggressive BCa and may inform future precision medicine genomic-based clinical studies. <em><\/em><\/p><p class=\"Pa7\"><em>Ethn Dis. <\/em>2017;27(1):169-178; doi:10.18865\/ed.27.2.169<\/p><\/jats:p>","DOI":"10.18865\/ed.27.2.169","type":"journal-article","created":{"date-parts":[[2017,4,20]],"date-time":"2017-04-20T10:06:02Z","timestamp":1492682762000},"page":"169","source":"Crossref","is-referenced-by-count":29,"title":["Next Generation Sequencing Reveals High Prevalence of BRCA1 and BRCA2 Variants of Unknown Significance in Early-Onset Breast Cancer in African American Women"],"prefix":"10.18865","volume":"27","author":[{"given":"Luisel","family":"Ricks-Santi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Tyson","family":"McDonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert","family":"Gold","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Dean","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muneer","family":"Abbas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Kanaan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammey J.","family":"Naab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Dunston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"18154","published-online":{"date-parts":[[2017,4,20]]},"container-title":["Ethnicity & Disease"],"original-title":[],"link":[{"URL":"https:\/\/www.ethndis.org\/edonline\/index.php\/ethndis\/article\/viewFile\/607\/821","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ethndis.org\/edonline\/index.php\/ethndis\/article\/viewFile\/607\/839","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ethndis.org\/edonline\/index.php\/ethndis\/article\/download\/607\/821","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,3,8]],"date-time":"2019-03-08T12:42:29Z","timestamp":1552048949000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ethndis.org\/edonline\/index.php\/ethndis\/article\/view\/607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4,20]]},"references-count":0,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,4,20]]}},"URL":"https:\/\/doi.org\/10.18865\/ed.27.2.169","relation":{},"ISSN":["1945-0826","1049-510X"],"issn-type":[{"value":"1945-0826","type":"electronic"},{"value":"1049-510X","type":"print"}],"subject":[],"published":{"date-parts":[[2017,4,20]]}}}