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Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers
Aggregation of genome-wide common risk variants, such as polygenic risk score (PRS), can measure genetic susceptibility to cancer. A better understanding of how common germline variants associate with somatic alterations and clinical features could facilitate personalized cancer prevention and early...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for Cancer Research
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811159/ https://www.ncbi.nlm.nih.gov/pubmed/36286845 http://dx.doi.org/10.1158/0008-5472.CAN-22-1492 |
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author | Namba, Shinichi Saito, Yuki Kogure, Yasunori Masuda, Tatsuo Bondy, Melissa L. Gharahkhani, Puya Gockel, Ines Heider, Dominik Hillmer, Axel Jankowski, Janusz MacGregor, Stuart Maj, Carlo Melin, Beatrice Ostrom, Quinn T. Palles, Claire Schumacher, Johannes Tomlinson, Ian Whiteman, David C. Okada, Yukinori Kataoka, Keisuke |
author_facet | Namba, Shinichi Saito, Yuki Kogure, Yasunori Masuda, Tatsuo Bondy, Melissa L. Gharahkhani, Puya Gockel, Ines Heider, Dominik Hillmer, Axel Jankowski, Janusz MacGregor, Stuart Maj, Carlo Melin, Beatrice Ostrom, Quinn T. Palles, Claire Schumacher, Johannes Tomlinson, Ian Whiteman, David C. Okada, Yukinori Kataoka, Keisuke |
author_sort | Namba, Shinichi |
collection | PubMed |
description | Aggregation of genome-wide common risk variants, such as polygenic risk score (PRS), can measure genetic susceptibility to cancer. A better understanding of how common germline variants associate with somatic alterations and clinical features could facilitate personalized cancer prevention and early detection. We constructed PRSs from 14 genome-wide association studies (median n = 64,905) for 12 cancer types by multiple methods and calibrated them using the UK Biobank resources (n = 335,048). Meta-analyses across cancer types in The Cancer Genome Atlas (n = 7,965) revealed that higher PRS values were associated with earlier cancer onset and lower burden of somatic alterations, including total mutations, chromosome/arm somatic copy-number alterations (SCNA), and focal SCNAs. This contrasts with rare germline pathogenic variants (e.g., BRCA1/2 variants), showing heterogeneous associations with somatic alterations. Our results suggest that common germline cancer risk variants allow early tumor development before the accumulation of many somatic alterations characteristic of later stages of carcinogenesis. SIGNIFICANCE: Meta-analyses across cancers show that common germline risk variants affect not only cancer predisposition but the age of cancer onset and burden of somatic alterations, including total mutations and copy-number alterations. |
format | Online Article Text |
id | pubmed-9811159 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-98111592023-02-08 Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers Namba, Shinichi Saito, Yuki Kogure, Yasunori Masuda, Tatsuo Bondy, Melissa L. Gharahkhani, Puya Gockel, Ines Heider, Dominik Hillmer, Axel Jankowski, Janusz MacGregor, Stuart Maj, Carlo Melin, Beatrice Ostrom, Quinn T. Palles, Claire Schumacher, Johannes Tomlinson, Ian Whiteman, David C. Okada, Yukinori Kataoka, Keisuke Cancer Res Priority Reports Aggregation of genome-wide common risk variants, such as polygenic risk score (PRS), can measure genetic susceptibility to cancer. A better understanding of how common germline variants associate with somatic alterations and clinical features could facilitate personalized cancer prevention and early detection. We constructed PRSs from 14 genome-wide association studies (median n = 64,905) for 12 cancer types by multiple methods and calibrated them using the UK Biobank resources (n = 335,048). Meta-analyses across cancer types in The Cancer Genome Atlas (n = 7,965) revealed that higher PRS values were associated with earlier cancer onset and lower burden of somatic alterations, including total mutations, chromosome/arm somatic copy-number alterations (SCNA), and focal SCNAs. This contrasts with rare germline pathogenic variants (e.g., BRCA1/2 variants), showing heterogeneous associations with somatic alterations. Our results suggest that common germline cancer risk variants allow early tumor development before the accumulation of many somatic alterations characteristic of later stages of carcinogenesis. SIGNIFICANCE: Meta-analyses across cancers show that common germline risk variants affect not only cancer predisposition but the age of cancer onset and burden of somatic alterations, including total mutations and copy-number alterations. American Association for Cancer Research 2023-01-04 2022-10-26 /pmc/articles/PMC9811159/ /pubmed/36286845 http://dx.doi.org/10.1158/0008-5472.CAN-22-1492 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
spellingShingle | Priority Reports Namba, Shinichi Saito, Yuki Kogure, Yasunori Masuda, Tatsuo Bondy, Melissa L. Gharahkhani, Puya Gockel, Ines Heider, Dominik Hillmer, Axel Jankowski, Janusz MacGregor, Stuart Maj, Carlo Melin, Beatrice Ostrom, Quinn T. Palles, Claire Schumacher, Johannes Tomlinson, Ian Whiteman, David C. Okada, Yukinori Kataoka, Keisuke Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers |
title | Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers |
title_full | Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers |
title_fullStr | Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers |
title_full_unstemmed | Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers |
title_short | Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers |
title_sort | common germline risk variants impact somatic alterations and clinical features across cancers |
topic | Priority Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811159/ https://www.ncbi.nlm.nih.gov/pubmed/36286845 http://dx.doi.org/10.1158/0008-5472.CAN-22-1492 |
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