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

PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Number of pages1
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Nov 5 2018

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Prostatic Neoplasms
cancer
magnetic permeability
chromosomes
loci
Chromosomes
stratification
Population

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium (2018). Germline variation at 8q24 and prostate cancer risk in men of European ancestry. Nature Communications, 9(1). https://doi.org/10.1038/s41467-018-06863-1

Germline variation at 8q24 and prostate cancer risk in men of European ancestry. / PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium.

In: Nature Communications, Vol. 9, No. 1, 05.11.2018.

Research output: Contribution to journalArticle

PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium 2018, 'Germline variation at 8q24 and prostate cancer risk in men of European ancestry', Nature Communications, vol. 9, no. 1. https://doi.org/10.1038/s41467-018-06863-1
PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium. Germline variation at 8q24 and prostate cancer risk in men of European ancestry. Nature Communications. 2018 Nov 5;9(1). https://doi.org/10.1038/s41467-018-06863-1
PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium. / Germline variation at 8q24 and prostate cancer risk in men of European ancestry. In: Nature Communications. 2018 ; Vol. 9, No. 1.
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abstract = "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.",
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