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Sökning: onr:"swepub:oai:DiVA.org:umu-203795" > Common germline ris...

Common germline risk variants impact somatic alterations and clinical features across cancers

Namba, Shinichi (författare)
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
Saito, Yuki (författare)
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan; Department of Gastroenterology, Keio University School of Medicine, Tokyo, Japan
Kogure, Yasunori (författare)
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan
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Masuda, Tatsuo (författare)
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan; Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Osaka, Japan; StemRIM Institute of Regeneration-Inducing Medicine, Osaka University, Osaka, Japan
Bondy, Melissa L. (författare)
Department of Epidemiology and Population Health, Stanford University School of Medicine, CA, Stanford, United States
Gharahkhani, Puya (författare)
Statistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, QLD, Brisbane, Australia
Gockel, Ines (författare)
Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany
Heider, Dominik (författare)
Department of Mathematics and Computer Science, University of Marburg, Marburg, Germany
Hillmer, Axel (författare)
Institute of Pathology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany
Jankowski, Janusz (författare)
Office of Vice President Research and Innovation, Laucala Bay Campus, University of South Pacific, Suva, Fiji; University College London, London, United Kingdom
MacGregor, Stuart (författare)
Statistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, QLD, Brisbane, Australia
Maj, Carlo (författare)
Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Bonn, Germany
Melin, Beatrice S. (författare)
Umeå universitet,Onkologi
Ostrom, Quinn T. (författare)
Department of Neurosurgery, Duke University School of Medicine, NC, Durham, United States; Preston Robert Tisch Brain Tumor Center, Duke University School of Medicine, NC, Durham, United States; Duke Cancer Institute, Duke University Medical Center, NC, Durham, United States
Palles, Claire (författare)
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom
Schumacher, Johannes (författare)
Center for Human Genetics, University Hospital of Marburg, Marburg, Germany
Tomlinson, Ian (författare)
Edinburgh Cancer Research Centre, IGMM, University of Edinburgh, Crewe Road, Edinburgh, United Kingdom
Whiteman, David C. (författare)
Cancer Control, QIMR Berghofer Medical Research Institute, QLD, Brisbane, Australia
Okada, Yukinori (författare)
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan; Department of Genome Informatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Suita, Japan; Center for Infectious Disease Education and Research (CiDER), Osaka University, Suita, Japan
Kataoka, Keisuke (författare)
Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan; Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan
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 (creator_code:org_t)
American Association for Cancer Research, 2023
2023
Engelska.
Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 83:1, s. 20-27
Relaterad länk:
https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

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