Namba, Shinichi ORCID: 0000-0002-7486-3146, Saito, Yuki ORCID: 0000-0003-2686-9604, Kogure, Yasunori ORCID: 0000-0003-1158-5131, Masuda, Tatsuo, Bondy, Melissa L., Gharahkhani, Puya ORCID: 0000-0002-4203-5952, Gockel, Ines, Heider, Dominik ORCID: 0000-0002-3108-8311, Hillmer, Axel, Jankowski, Janusz ORCID: 0000-0003-2130-9181, MacGregor, Stuart, Maj, Carlo, Melin, Beatrice, Ostrom, Quinn T., Palles, Claire, Schumacher, Johannes, Tomlinson, Ian, Whiteman, David C., Okada, Yukinori and Kataoka, Keisuke (2022). Common Germline Risk Variants Impact Somatic Alterations and Clinical Features across Cancers. Cancer Res., 83 (1). S. 20 - 28. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 1538-7445

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Namba, ShinichiUNSPECIFIEDorcid.org/0000-0002-7486-3146UNSPECIFIED
Saito, YukiUNSPECIFIEDorcid.org/0000-0003-2686-9604UNSPECIFIED
Kogure, YasunoriUNSPECIFIEDorcid.org/0000-0003-1158-5131UNSPECIFIED
Masuda, TatsuoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bondy, Melissa L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gharahkhani, PuyaUNSPECIFIEDorcid.org/0000-0002-4203-5952UNSPECIFIED
Gockel, InesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heider, DominikUNSPECIFIEDorcid.org/0000-0002-3108-8311UNSPECIFIED
Hillmer, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jankowski, JanuszUNSPECIFIEDorcid.org/0000-0003-2130-9181UNSPECIFIED
MacGregor, StuartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maj, CarloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Melin, BeatriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ostrom, Quinn T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Palles, ClaireUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schumacher, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tomlinson, IanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Whiteman, David C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Okada, YukinoriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kataoka, KeisukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-695889
DOI: 10.1158/0008-5472.CAN-22-1492
Journal or Publication Title: Cancer Res.
Volume: 83
Number: 1
Page Range: S. 20 - 28
Date: 2022
Publisher: AMER ASSOC CANCER RESEARCH
Place of Publication: PHILADELPHIA
ISSN: 1538-7445
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SCORES; ASSOCIATIONMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69588

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