A Population-Based Analysis of <i>BRCA1</i>/<i>2</i> Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study
In this study, we performed a comprehensive analysis of <i>BRCA1</i>/<i>2</i> variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic or likely pathogenic variants (PLPVs) in <i>BRCA1</i&...
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MDPI AG
2021-05-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/9/2192 |
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| author | Kyung-Sun Park Woochang Lee Moon-Woo Seong Sun-Young Kong Kyung-A Lee Jung-Sook Ha Eun-Hae Cho Sung-Hee Han Inho Park Jong-Won Kim |
| author_facet | Kyung-Sun Park Woochang Lee Moon-Woo Seong Sun-Young Kong Kyung-A Lee Jung-Sook Ha Eun-Hae Cho Sung-Hee Han Inho Park Jong-Won Kim |
| author_sort | Kyung-Sun Park |
| collection | DOAJ |
| description | In this study, we performed a comprehensive analysis of <i>BRCA1</i>/<i>2</i> variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic or likely pathogenic variants (PLPVs) in <i>BRCA1</i> and <i>BRCA2</i>. This study included 5433 Korean participants who were tested for <i>BRCA1/2</i> genes. The <i>BRCA1/2</i> variants were classified following the standards/guidelines for interpretation of genetic variants and using a multifactorial probability-based approach. In Korea, 15.8% of participants had <i>BRCA1</i> or <i>BRCA2</i> PLPVs. To estimate the additional sample numbers needed to resolve unclassified status, we applied a simulation analysis. The simulation study for VUS showed that the smaller the number of samples, the more the posterior probability was affected by the prior probability; in addition, more samples for <i>BRCA2</i> VUS than those of <i>BRCA1</i> VUS were required to resolve the unclassified status, and the presence of clinical information associated with their VUS was an important factor. The cumulative lifetime breast cancer risk was 59.1% (95% CI: 44.1–73.6%) for <i>BRCA1</i> and 58.3% (95% CI: 43.2–73.0%) for <i>BRCA2</i> carriers. The cumulative lifetime ovarian cancer risk was estimated to be 36.9% (95% CI: 23.4–53.9%) for <i>BRCA1</i> and 14.9% (95% CI: 7.4–28.5%) for <i>BRCA2</i> carriers. |
| first_indexed | 2024-03-10T11:44:09Z |
| format | Article |
| id | doaj.art-422dcb320dd549b0baaf6c934bf02834 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T11:44:09Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-422dcb320dd549b0baaf6c934bf028342023-11-21T18:13:42ZengMDPI AGCancers2072-66942021-05-01139219210.3390/cancers13092192A Population-Based Analysis of <i>BRCA1</i>/<i>2</i> Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort StudyKyung-Sun Park0Woochang Lee1Moon-Woo Seong2Sun-Young Kong3Kyung-A Lee4Jung-Sook Ha5Eun-Hae Cho6Sung-Hee Han7Inho Park8Jong-Won Kim9Department of Laboratory Medicine, Kyung Hee University School of Medicine and Kyung Hee University Medical Center, Seoul 02447, KoreaDepartment of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, KoreaDepartment of Laboratory Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, KoreaDivision of Translational Science, Research Institute, National Cancer Center, Goyang 10408, KoreaDepartment of Laboratory Medicine, Yonsei University College of Medicine, Seoul 06273, KoreaDepartment of Laboratory Medicine, Keimyung University School of Medicine, Daegu 41931, KoreaGenomic Research Center, GC Genome, Yongin 16924, KoreaBiotechnology Division, BioCore Co. Ltd., Yongin 16954, KoreaDepartment of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, KoreaDepartment of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaIn this study, we performed a comprehensive analysis of <i>BRCA1</i>/<i>2</i> variants and associated cancer risk in Korean patients considering two aspects: variants of uncertain significance (VUS) and pathogenic or likely pathogenic variants (PLPVs) in <i>BRCA1</i> and <i>BRCA2</i>. This study included 5433 Korean participants who were tested for <i>BRCA1/2</i> genes. The <i>BRCA1/2</i> variants were classified following the standards/guidelines for interpretation of genetic variants and using a multifactorial probability-based approach. In Korea, 15.8% of participants had <i>BRCA1</i> or <i>BRCA2</i> PLPVs. To estimate the additional sample numbers needed to resolve unclassified status, we applied a simulation analysis. The simulation study for VUS showed that the smaller the number of samples, the more the posterior probability was affected by the prior probability; in addition, more samples for <i>BRCA2</i> VUS than those of <i>BRCA1</i> VUS were required to resolve the unclassified status, and the presence of clinical information associated with their VUS was an important factor. The cumulative lifetime breast cancer risk was 59.1% (95% CI: 44.1–73.6%) for <i>BRCA1</i> and 58.3% (95% CI: 43.2–73.0%) for <i>BRCA2</i> carriers. The cumulative lifetime ovarian cancer risk was estimated to be 36.9% (95% CI: 23.4–53.9%) for <i>BRCA1</i> and 14.9% (95% CI: 7.4–28.5%) for <i>BRCA2</i> carriers.https://www.mdpi.com/2072-6694/13/9/2192<i>BRCA1</i><i>BRCA2</i>breast cancerovarian cancervariants of uncertain significancecumulative risk |
| spellingShingle | Kyung-Sun Park Woochang Lee Moon-Woo Seong Sun-Young Kong Kyung-A Lee Jung-Sook Ha Eun-Hae Cho Sung-Hee Han Inho Park Jong-Won Kim A Population-Based Analysis of <i>BRCA1</i>/<i>2</i> Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study Cancers <i>BRCA1</i> <i>BRCA2</i> breast cancer ovarian cancer variants of uncertain significance cumulative risk |
| title | A Population-Based Analysis of <i>BRCA1</i>/<i>2</i> Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study |
| title_full | A Population-Based Analysis of <i>BRCA1</i>/<i>2</i> Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study |
| title_fullStr | A Population-Based Analysis of <i>BRCA1</i>/<i>2</i> Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study |
| title_full_unstemmed | A Population-Based Analysis of <i>BRCA1</i>/<i>2</i> Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study |
| title_short | A Population-Based Analysis of <i>BRCA1</i>/<i>2</i> Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study |
| title_sort | population based analysis of i brca1 i i 2 i genes and associated breast and ovarian cancer risk in korean patients a multicenter cohort study |
| topic | <i>BRCA1</i> <i>BRCA2</i> breast cancer ovarian cancer variants of uncertain significance cumulative risk |
| url | https://www.mdpi.com/2072-6694/13/9/2192 |
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