Search for genetic factor association with cancer-free prostate-specific antigen level elevation on the basis of a genome-wide association study in the Korean population

Eun Kyung Choe, Young Lee, Jeong Yeon Cho, Seung Ho Choi, Boram Park, Jong Eun Lee, Eun Young Cho

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

We investigated the genetic markers associated with elevated serum prostate-specific antigen (sPSA) levels to improve the predictive power of sPSA in screening for prostate cancer. A genome-wide association study was carried out among 4124 healthy Korean male adults using the Affymetrix Axiom Customized Biobank Genotyping Arrays for sPSA levels. A subgroup analysis for increased sPSA levels who underwent a prostate biopsy (n=64) was also carried out. We detected 11 single nucleotide polymorphisms (SNPs) near the Solute carrier family 45member 3, AGAP7P, MSMB, LOC101929917, and KLK3 genes associated with sPSA levels. The top SNP associated with the log of the sPSA levels was rs72434280 in the Solute carrier family 45 member 3 gene (P value, discovery set=2.98×10 -20, replication set=7.31×10 -10). A case-control study utilizing available biopsy reports (49 patients with normal biopsies vs. 15 patients with biopsies indicating cancer) for the sPSA more than 3 ng/ml group was carried out for the respective SNPs after adjusting for age. Only the SNPs near the KLK3 gene were associated with prostate cancer. In the model of the predictive elevation of sPSA level, adding the genetic risk score [area under the curve (AUC)=0.697] to age and BMI (AUC=0.602) significantly improved the results of the AUC (P<0.0001). We found seven SNPs associated with elevated prostate-specific antigen levels in healthy Korean men. Four SNPs were a novel marker in the Korean population. In men with increased prostate-specific antigen levels, genotyping SNP related to cancer-free elevation of sPSA level could be informative to decide the indication of prostate biopsy.

Original languageEnglish
Pages (from-to)453-460
Number of pages8
JournalEuropean Journal of Cancer Prevention
Volume27
Issue number5
DOIs
StatePublished - 1 Sep 2018

Fingerprint

Genome-Wide Association Study
Prostate-Specific Antigen
Prostatic Neoplasms
Single Nucleotide Polymorphism
Population
Serum
Biopsy
Area Under Curve
Prostate
Genes
Genetic Markers
Case-Control Studies

Keywords

  • prostate cancer
  • prostate-specific antigen
  • screening
  • single nucleotide polymorphism

Cite this

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title = "Search for genetic factor association with cancer-free prostate-specific antigen level elevation on the basis of a genome-wide association study in the Korean population",
abstract = "We investigated the genetic markers associated with elevated serum prostate-specific antigen (sPSA) levels to improve the predictive power of sPSA in screening for prostate cancer. A genome-wide association study was carried out among 4124 healthy Korean male adults using the Affymetrix Axiom Customized Biobank Genotyping Arrays for sPSA levels. A subgroup analysis for increased sPSA levels who underwent a prostate biopsy (n=64) was also carried out. We detected 11 single nucleotide polymorphisms (SNPs) near the Solute carrier family 45member 3, AGAP7P, MSMB, LOC101929917, and KLK3 genes associated with sPSA levels. The top SNP associated with the log of the sPSA levels was rs72434280 in the Solute carrier family 45 member 3 gene (P value, discovery set=2.98×10 -20, replication set=7.31×10 -10). A case-control study utilizing available biopsy reports (49 patients with normal biopsies vs. 15 patients with biopsies indicating cancer) for the sPSA more than 3 ng/ml group was carried out for the respective SNPs after adjusting for age. Only the SNPs near the KLK3 gene were associated with prostate cancer. In the model of the predictive elevation of sPSA level, adding the genetic risk score [area under the curve (AUC)=0.697] to age and BMI (AUC=0.602) significantly improved the results of the AUC (P<0.0001). We found seven SNPs associated with elevated prostate-specific antigen levels in healthy Korean men. Four SNPs were a novel marker in the Korean population. In men with increased prostate-specific antigen levels, genotyping SNP related to cancer-free elevation of sPSA level could be informative to decide the indication of prostate biopsy.",
keywords = "prostate cancer, prostate-specific antigen, screening, single nucleotide polymorphism",
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Search for genetic factor association with cancer-free prostate-specific antigen level elevation on the basis of a genome-wide association study in the Korean population. / Choe, Eun Kyung; Lee, Young; Cho, Jeong Yeon; Choi, Seung Ho; Park, Boram; Lee, Jong Eun; Cho, Eun Young.

In: European Journal of Cancer Prevention, Vol. 27, No. 5, 01.09.2018, p. 453-460.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Cho, Eun Young

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