Germline variation at 8q24 and prostate cancer risk in men of European ancestry

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http://hdl.handle.net/10138/300056

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The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium , Matejcic , M , Saunders , E J & Taari , K O 2018 , ' Germline variation at 8q24 and prostate cancer risk in men of European ancestry ' , Nature Communications , vol. 9 , no. 1 , 4616 . https://doi.org/10.1038/s41467-018-06863-1

Titel: Germline variation at 8q24 and prostate cancer risk in men of European ancestry
Författare: The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; Matejcic, Marco; Saunders, Edward J.; Taari, Kimmo Olavi
Upphovmannens organisation: University Management
Clinicum
HUS Abdominal Center
Datum: 2018-11-05
Språk: eng
Sidantal: 11
Tillhör serie: Nature Communications
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-06863-1
Permanenta länken (URI): http://hdl.handle.net/10138/300056
Abstrakt: Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10 −15 ), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification. © 2018, The Author(s).Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10 −15 ), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification. © 2018, The Author(s).
Beskrivning: An Author Correction to this article was published on 17 January 2019.
Subject: 3122 Cancers
3126 Surgery, anesthesiology, intensive care, radiology
Referentgranskad: Ja
Licens: cc_by
Användningsbegränsning: openAccess
Parallelpublicerad version: publishedVersion


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