Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

for the PRACTICAL/ELLIPSE Consortium

Research output: Contribution to journalArticle

Abstract

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancerin men of African ancestry, we performed a genome-wide associationmeta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects.We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10×10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR=1.62, 95% CI=1.39 to 1.89, P = 7.50×10-10). At 13q34, the signal is located 5′ of the gene IRS2 and 3′ of a long noncoding RNA, while at 22q12 the candidate functional allele is amissense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

Original languageEnglish (US)
Article numberdjx084
JournalJournal of the National Cancer Institute
Volume109
Issue number8
DOIs
StatePublished - Aug 1 2017

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Prostatic Neoplasms
Gene Frequency
Alleles
Odds Ratio
Long Noncoding RNA
Confidence Intervals
African Americans
Population
Genes
Prostate
Chromosomes
Genome
Incidence

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry. / for the PRACTICAL/ELLIPSE Consortium.

In: Journal of the National Cancer Institute, Vol. 109, No. 8, djx084, 01.08.2017.

Research output: Contribution to journalArticle

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abstract = "Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancerin men of African ancestry, we performed a genome-wide associationmeta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects.We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2{\%}, odds ratio [OR] = 1.55, 95{\%} confidence interval [CI] = 1.37 to 1.76, P = 6.10×10-12; 22q12.1: rs78554043, risk allele frequency = 1.5{\%}, OR=1.62, 95{\%} CI=1.39 to 1.89, P = 7.50×10-10). At 13q34, the signal is located 5′ of the gene IRS2 and 3′ of a long noncoding RNA, while at 22q12 the candidate functional allele is amissense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.",
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