دورية أكاديمية
Influence of family history on penetrance of hereditary cancers in a population setting
| العنوان: | Influence of family history on penetrance of hereditary cancers in a population setting |
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| المؤلفون: | Jackson, L, Weedon, MN, Green, HD, Mallabar-Rimmer, B, Harrison, JW, Wood, AR, Ruth, KS, Tyrrell, J, Wright, CF |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2023 |
| المجموعة: | University of Exeter: Open Research Exeter (ORE) |
| مصطلحات موضوعية: | BRCA, Family history, Inheritance, Lynch syndrome, Penetrance |
| الوصف: | This is the final version. Available on open access from Elsevier via the DOI in this record ; Data sharing statement: All data used in this study can be accessed via application to UK Biobank and approval via the data access committee. The authors are not permitted to directly share this data. The code used to perform GRS is available at https://github.com/hdg204/Rdna-nexusTest. Variants classified as pathogenic and used in this study are defined in the methods and can be replicated, however a list is available on request. ; BACKGROUND: We sought to investigate how penetrance of familial cancer syndromes varies with family history using a population-based cohort. METHODS: We analysed 454,712 UK Biobank participants with exome sequence and clinical data (data collected between March 2006 and June 2021). We identified participants with a self-reported family history of breast or colorectal cancer and a pathogenic/likely pathogenic variant in the major genes responsible for hereditary breast cancer or Lynch syndrome. We calculated survival to cancer diagnosis (controlled for sex, death, recruitment centre, screening and prophylactic surgery). FINDINGS: Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2-59.3 and 24.1%, CI 17.5-32.6) versus those without (22.8%, CI 15.9-32.0 and 17.9%, CI 13.8-23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) than those without (13.0, 15.4 and 7.2). Penetrance to age 60 was also higher for carriers of a pathogenic MLH1 or MSH2 variant in those with a family history (30.9%, CI 18.1-49.3 and 38.3%, CI 21.5-61.8) versus those without ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 102159-; Electronic-eCollection |
| اللغة: | English |
| تدمد: | 2589-5370 |
| العلاقة: | https://github.com/hdg204/Rdna-nexusTest; https://www.ncbi.nlm.nih.gov/pubmed/37936660Test; EClinicalMedicine, 64; orcid:0000-0002-0260-5295 (Jackson, Leigh); orcid:0000-0002-5105-184X (Green, Harry D); ScopusID: 57208081135 (Green, Harry D); orcid:0000-0002-8314-9411 (Harrison, Jamie W); orcid:0000-0003-4966-9170 (Ruth, Kate S); ScopusID: 56661968700 (Ruth, Kate S); orcid:0000-0002-9256-6065 (Tyrrell, Jess); orcid:0000-0003-2958-5076 (Wright, Caroline F); ScopusID: 35175170800 (Wright, Caroline F); Vol. 64, article 102159; https://doi.org/10.1016/j.eclinm.2023.102159Test; MR/T00200X/1; http://hdl.handle.net/10871/134907Test; EClinicalMedicine |
| DOI: | 10.1016/j.eclinm.2023.102159 |
| الإتاحة: | https://doi.org/10.1016/j.eclinm.2023.102159Test http://hdl.handle.net/10871/134907Test |
| حقوق: | © 2023 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0Test/) ; https://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; CC BY |
| رقم الانضمام: | edsbas.AB6846AC |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 25895370 |
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| DOI: | 10.1016/j.eclinm.2023.102159 |