Regional Differences in the Frequency of BRCA1 and BRCA2 Variants in Northeastern Japan: A Cohort Study
ABSTRACT Background Germline mutations in BRCA1/2 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 BRCA1/2 variants have b...
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Wiley
2025-04-01
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| Online Access: | https://doi.org/10.1002/cam4.70443 |
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| author | Hidekazu Shirota Akimitsu Miyake Maako Kawamura Shuhei Suzuki Kensuke Saito Jun Yasuda Hiroyuki Shibata Motonobu Saito Takeshi Iwaya Hiroshi Tada Muneaki Shimada Naoki Kawamorita Masayuki Kanamori Eisaku Miyauchi Hidetaka Niizuma Tomoyuki Iwasaki Yuki Kasahara Hiroo Imai Ken Saijo Keigo Komine Masanobu Takahashi Tetsuya Niihori Yoko Aoki Toru Furukawa Gen Tamiya Chikashi Ishioka |
| author_facet | Hidekazu Shirota Akimitsu Miyake Maako Kawamura Shuhei Suzuki Kensuke Saito Jun Yasuda Hiroyuki Shibata Motonobu Saito Takeshi Iwaya Hiroshi Tada Muneaki Shimada Naoki Kawamorita Masayuki Kanamori Eisaku Miyauchi Hidetaka Niizuma Tomoyuki Iwasaki Yuki Kasahara Hiroo Imai Ken Saijo Keigo Komine Masanobu Takahashi Tetsuya Niihori Yoko Aoki Toru Furukawa Gen Tamiya Chikashi Ishioka |
| author_sort | Hidekazu Shirota |
| collection | DOAJ |
| description | ABSTRACT Background Germline mutations in BRCA1/2 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 BRCA1/2 variants have been identified. Methods In this study, we extracted and analyzed cases of BRCA1/2 variants that were presumed to be germline, which were repeatedly detected using the CGP test for solid tumors in northeastern Japan. The frequencies of BRCA1/2 variants in regional areas were compared with those of healthy individuals or nationwide cancer cohorts to investigate regional distribution. Results Our findings revealed regional disparities in BRCA1/2 pathogenic germline variants, while variants of unknown significance (VUS) showed no such differences. The regional distribution of BRCA1 and BRCA2 variants showed distinct patterns: pathogenic variants of BRCA1 exhibited regional differences and were less prevalent compared to VUS, whereas BRCA2 variants, including both pathogenic variants and VUS, did not exhibit such clear regional localization. This discrepancy in regional distribution between BRCA1 and BRCA2 variants could be attributed to factors such as the diversity of the genome, gender differences, and cancer types. Conclusions 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. |
| format | Article |
| id | doaj-art-30b130dee5d24e50adb920de018adf50 |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-04-01 |
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| series | Cancer Medicine |
| spelling | doaj-art-30b130dee5d24e50adb920de018adf502025-08-20T03:15:05ZengWileyCancer Medicine2045-76342025-04-01148n/an/a10.1002/cam4.70443Regional Differences in the Frequency of BRCA1 and BRCA2 Variants in Northeastern Japan: A Cohort StudyHidekazu Shirota0Akimitsu Miyake1Maako Kawamura2Shuhei Suzuki3Kensuke Saito4Jun Yasuda5Hiroyuki Shibata6Motonobu Saito7Takeshi Iwaya8Hiroshi Tada9Muneaki Shimada10Naoki Kawamorita11Masayuki Kanamori12Eisaku Miyauchi13Hidetaka Niizuma14Tomoyuki Iwasaki15Yuki Kasahara16Hiroo Imai17Ken Saijo18Keigo Komine19Masanobu Takahashi20Tetsuya Niihori21Yoko Aoki22Toru Furukawa23Gen Tamiya24Chikashi Ishioka25Department of Medical Oncology Tohoku University Hospital Sendai JapanTohoku Medical Megabank Organization Tohoku University Sendai JapanPersonalized Medicine Center Tohoku University Hospital Sendai JapanDepartment of Clinical Oncology Yamagata University Faculty of Medicine Yamagata JapanDepartment of Medical Oncology Hirosaki University Graduate School of Medicine Hirosaki JapanDivision of Molecular Cellular Oncology Miyagi Cancer Center Research Institute Natori JapanDepartment of Clinical Oncology, Graduate School of Medicine Akita University Akita JapanDepartment of Gastrointestinal Tract Surgery Fukushima Medical University School of Medicine Fukushima JapanDepartment of Clinical Oncology Iwate Medical University School of Medicine Morioka JapanDepartment of Breast and Endocrine Surgical Oncology Tohoku University Graduate School of Medicine Sendai JapanDepartment of Obstetrics and Gynecology Tohoku University School of Medicine Sendai JapanDepartment of Urology Tohoku University School of Medicine Sendai JapanDepartment of Neurosurgery Tohoku University School of Medicine Sendai JapanDepartment of Respiratory Medicine Tohoku University Graduate School of Medicine Sendai JapanDepartment of Pediatrics Tohoku University School of Medicine Sendai JapanDepartment of Medical Oncology Tohoku University Hospital Sendai JapanDepartment of Medical Oncology Tohoku University Hospital Sendai JapanDepartment of Medical Oncology Tohoku University Hospital Sendai JapanDepartment of Medical Oncology Tohoku University Hospital Sendai JapanDepartment of Medical Oncology Tohoku University Hospital Sendai JapanDepartment of Medical Oncology Tohoku University Hospital Sendai JapanDepartment of Medical Genetics Tohoku University Graduate School of Medicine Sendai JapanDepartment of Medical Genetics Tohoku University Graduate School of Medicine Sendai JapanDepartment of Investigative Pathology Tohoku University Graduate School of Medicine Sendai JapanTohoku Medical Megabank Organization Tohoku University Sendai JapanDepartment of Medical Oncology Tohoku University Hospital Sendai JapanABSTRACT Background Germline mutations in BRCA1/2 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 BRCA1/2 variants have been identified. Methods In this study, we extracted and analyzed cases of BRCA1/2 variants that were presumed to be germline, which were repeatedly detected using the CGP test for solid tumors in northeastern Japan. The frequencies of BRCA1/2 variants in regional areas were compared with those of healthy individuals or nationwide cancer cohorts to investigate regional distribution. Results Our findings revealed regional disparities in BRCA1/2 pathogenic germline variants, while variants of unknown significance (VUS) showed no such differences. The regional distribution of BRCA1 and BRCA2 variants showed distinct patterns: pathogenic variants of BRCA1 exhibited regional differences and were less prevalent compared to VUS, whereas BRCA2 variants, including both pathogenic variants and VUS, did not exhibit such clear regional localization. This discrepancy in regional distribution between BRCA1 and BRCA2 variants could be attributed to factors such as the diversity of the genome, gender differences, and cancer types. Conclusions 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.https://doi.org/10.1002/cam4.70443BRCA1BRCA2CGP testgeographical distributionsolid tumor |
| spellingShingle | Hidekazu Shirota Akimitsu Miyake Maako Kawamura Shuhei Suzuki Kensuke Saito Jun Yasuda Hiroyuki Shibata Motonobu Saito Takeshi Iwaya Hiroshi Tada Muneaki Shimada Naoki Kawamorita Masayuki Kanamori Eisaku Miyauchi Hidetaka Niizuma Tomoyuki Iwasaki Yuki Kasahara Hiroo Imai Ken Saijo Keigo Komine Masanobu Takahashi Tetsuya Niihori Yoko Aoki Toru Furukawa Gen Tamiya Chikashi Ishioka Regional Differences in the Frequency of BRCA1 and BRCA2 Variants in Northeastern Japan: A Cohort Study Cancer Medicine BRCA1 BRCA2 CGP test geographical distribution solid tumor |
| title | Regional Differences in the Frequency of BRCA1 and BRCA2 Variants in Northeastern Japan: A Cohort Study |
| title_full | Regional Differences in the Frequency of BRCA1 and BRCA2 Variants in Northeastern Japan: A Cohort Study |
| title_fullStr | Regional Differences in the Frequency of BRCA1 and BRCA2 Variants in Northeastern Japan: A Cohort Study |
| title_full_unstemmed | Regional Differences in the Frequency of BRCA1 and BRCA2 Variants in Northeastern Japan: A Cohort Study |
| title_short | Regional Differences in the Frequency of BRCA1 and BRCA2 Variants in Northeastern Japan: A Cohort Study |
| title_sort | regional differences in the frequency of brca1 and brca2 variants in northeastern japan a cohort study |
| topic | BRCA1 BRCA2 CGP test geographical distribution solid tumor |
| url | https://doi.org/10.1002/cam4.70443 |
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