{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:29:06Z","timestamp":1780414146857,"version":"3.54.1"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Germline mutations in <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> are known to cause hereditary tumors in the breast, ovary, and other organs. With the widespread adoption of comprehensive diagnostics, including comprehensive genomic profiling (CGP) tests for solid tumors, many patients with <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> variants have been identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we extracted and analyzed cases of <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> variants that were presumed to be germline, which were repeatedly detected using the CGP test for solid tumors in northeastern Japan. The frequencies of <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> variants in regional areas were compared with those of healthy individuals or nationwide cancer cohorts to investigate regional distribution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings revealed regional disparities in <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> pathogenic germline variants, while variants of unknown significance (VUS) showed no such differences. The regional distribution of <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> variants showed distinct patterns: pathogenic variants of <jats:italic>BRCA1<\/jats:italic> exhibited regional differences and were less prevalent compared to VUS, whereas <jats:italic>BRCA2<\/jats:italic> variants, including both pathogenic variants and VUS, did not exhibit such clear regional localization. This discrepancy in regional distribution between <jats:italic>BRCA1<\/jats:italic> and <jats:italic>BRCA2<\/jats:italic> variants could be attributed to factors such as the diversity of the genome, gender differences, and cancer types.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results highlight the importance of considering regional differences in comparative cohort studies, particularly in assessing the differential extension of mutations in pathogenic changes and VUS. Moreover, a presumption of pathogenicity variants would need to be discussed at the regional level.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.70443","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T14:36:01Z","timestamp":1744986961000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Regional Differences in the Frequency of <scp><i>BRCA1<\/i><\/scp> and <scp><i>BRCA2<\/i><\/scp> Variants in Northeastern Japan: A Cohort Study"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9154-9004","authenticated-orcid":false,"given":"Hidekazu","family":"Shirota","sequence":"first","affiliation":[{"name":"Department of Medical Oncology Tohoku University Hospital  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akimitsu","family":"Miyake","sequence":"additional","affiliation":[{"name":"Tohoku Medical Megabank Organization 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