Genome-wide association study identifies loci at ATF7IP and KLK2 associated with percentage of circulating free PSA

Guangfu Jin, Siqun Lilly Zheng, Hans Lilja, Seong Tae Kim, Sha Tao, Zhengrong Gao, Tracey Young, Fredrik Wiklund, Junjie Feng, William B Isaacs, Roger S. Rittmaster, Henrik Gronberg, Lynn D. Condreay, Jielin Sun, Jianfeng Xu

Research output: Contribution to journalArticle

Abstract

Background: Percentage of free-to-total prostate-specific antigen (%fPSA) is an independent predictor of risk for prostate cancer among men with modestly elevated level of total PSA (tPSA) in blood. Physiological and pathological factors have been shown to influence the %fPSA value and diagnostic accuracy. Materials/Methods: To evaluate genetic determinants of %fPSA, we conducted a genome-wide association study of serum %fPSA by genotyping 642,584 single nucleotide polymorphisms (SNPs) in 3192 men of European ancestry, each with a tPSA level of 2.5 to 10 ng/ml, that were recruited in the REduction by DUtasteride of Prostate Cancer Events study. Single nucleotide polymorphisms (SNPs) with P <10-5 were further evaluated among the controls of a population-based case-control study in Sweden (2899 prostate cancer cases and 1722 male controls), including 464 controls having tPSA levels of 2.5 to 10 ng/ml. Results: We identified two loci that were associated with %fPSA at a genome-wide significance level (P-8). The first associated SNP was rs3213764 (P= 6.45×10-10), a nonsynonymous variant (K530R) in the ATF7IP gene at 12p13. This variant was also nominally associated with tPSA (P =.015). The second locus was rs1354774 (P = 1.25 × 10-12), near KLK2 at 19q13, which was not associated with tPSA levels, and is separate from the rs17632542 locus at KLK3 that was previously associated with tPSA levels and prostate cancer risk. Neither rs3213764 nor rs1354774 was associated with prostate cancer risk or aggressiveness. Conclusions: These findings demonstrate that genetic variants at ATF7IP and KLK2 contribute to the variance of %fPSA.

Original languageEnglish (US)
Pages (from-to)95-101
Number of pages7
JournalNeoplasia
Volume15
Issue number1
DOIs
StatePublished - Jan 2013

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Genome-Wide Association Study
Prostatic Neoplasms
Single Nucleotide Polymorphism
Prostate-Specific Antigen
Sweden
Case-Control Studies
Genome
Serum
Population
Genes

ASJC Scopus subject areas

  • Cancer Research

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Genome-wide association study identifies loci at ATF7IP and KLK2 associated with percentage of circulating free PSA. / Jin, Guangfu; Zheng, Siqun Lilly; Lilja, Hans; Kim, Seong Tae; Tao, Sha; Gao, Zhengrong; Young, Tracey; Wiklund, Fredrik; Feng, Junjie; Isaacs, William B; Rittmaster, Roger S.; Gronberg, Henrik; Condreay, Lynn D.; Sun, Jielin; Xu, Jianfeng.

In: Neoplasia, Vol. 15, No. 1, 01.2013, p. 95-101.

Research output: Contribution to journalArticle

Jin, G, Zheng, SL, Lilja, H, Kim, ST, Tao, S, Gao, Z, Young, T, Wiklund, F, Feng, J, Isaacs, WB, Rittmaster, RS, Gronberg, H, Condreay, LD, Sun, J & Xu, J 2013, 'Genome-wide association study identifies loci at ATF7IP and KLK2 associated with percentage of circulating free PSA', Neoplasia, vol. 15, no. 1, pp. 95-101. https://doi.org/10.1593/neo.121620
Jin, Guangfu ; Zheng, Siqun Lilly ; Lilja, Hans ; Kim, Seong Tae ; Tao, Sha ; Gao, Zhengrong ; Young, Tracey ; Wiklund, Fredrik ; Feng, Junjie ; Isaacs, William B ; Rittmaster, Roger S. ; Gronberg, Henrik ; Condreay, Lynn D. ; Sun, Jielin ; Xu, Jianfeng. / Genome-wide association study identifies loci at ATF7IP and KLK2 associated with percentage of circulating free PSA. In: Neoplasia. 2013 ; Vol. 15, No. 1. pp. 95-101.
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title = "Genome-wide association study identifies loci at ATF7IP and KLK2 associated with percentage of circulating free PSA",
abstract = "Background: Percentage of free-to-total prostate-specific antigen ({\%}fPSA) is an independent predictor of risk for prostate cancer among men with modestly elevated level of total PSA (tPSA) in blood. Physiological and pathological factors have been shown to influence the {\%}fPSA value and diagnostic accuracy. Materials/Methods: To evaluate genetic determinants of {\%}fPSA, we conducted a genome-wide association study of serum {\%}fPSA by genotyping 642,584 single nucleotide polymorphisms (SNPs) in 3192 men of European ancestry, each with a tPSA level of 2.5 to 10 ng/ml, that were recruited in the REduction by DUtasteride of Prostate Cancer Events study. Single nucleotide polymorphisms (SNPs) with P <10-5 were further evaluated among the controls of a population-based case-control study in Sweden (2899 prostate cancer cases and 1722 male controls), including 464 controls having tPSA levels of 2.5 to 10 ng/ml. Results: We identified two loci that were associated with {\%}fPSA at a genome-wide significance level (P-8). The first associated SNP was rs3213764 (P= 6.45×10-10), a nonsynonymous variant (K530R) in the ATF7IP gene at 12p13. This variant was also nominally associated with tPSA (P =.015). The second locus was rs1354774 (P = 1.25 × 10-12), near KLK2 at 19q13, which was not associated with tPSA levels, and is separate from the rs17632542 locus at KLK3 that was previously associated with tPSA levels and prostate cancer risk. Neither rs3213764 nor rs1354774 was associated with prostate cancer risk or aggressiveness. Conclusions: These findings demonstrate that genetic variants at ATF7IP and KLK2 contribute to the variance of {\%}fPSA.",
author = "Guangfu Jin and Zheng, {Siqun Lilly} and Hans Lilja and Kim, {Seong Tae} and Sha Tao and Zhengrong Gao and Tracey Young and Fredrik Wiklund and Junjie Feng and Isaacs, {William B} and Rittmaster, {Roger S.} and Henrik Gronberg and Condreay, {Lynn D.} and Jielin Sun and Jianfeng Xu",
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T1 - Genome-wide association study identifies loci at ATF7IP and KLK2 associated with percentage of circulating free PSA

AU - Jin, Guangfu

AU - Zheng, Siqun Lilly

AU - Lilja, Hans

AU - Kim, Seong Tae

AU - Tao, Sha

AU - Gao, Zhengrong

AU - Young, Tracey

AU - Wiklund, Fredrik

AU - Feng, Junjie

AU - Isaacs, William B

AU - Rittmaster, Roger S.

AU - Gronberg, Henrik

AU - Condreay, Lynn D.

AU - Sun, Jielin

AU - Xu, Jianfeng

PY - 2013/1

Y1 - 2013/1

N2 - Background: Percentage of free-to-total prostate-specific antigen (%fPSA) is an independent predictor of risk for prostate cancer among men with modestly elevated level of total PSA (tPSA) in blood. Physiological and pathological factors have been shown to influence the %fPSA value and diagnostic accuracy. Materials/Methods: To evaluate genetic determinants of %fPSA, we conducted a genome-wide association study of serum %fPSA by genotyping 642,584 single nucleotide polymorphisms (SNPs) in 3192 men of European ancestry, each with a tPSA level of 2.5 to 10 ng/ml, that were recruited in the REduction by DUtasteride of Prostate Cancer Events study. Single nucleotide polymorphisms (SNPs) with P <10-5 were further evaluated among the controls of a population-based case-control study in Sweden (2899 prostate cancer cases and 1722 male controls), including 464 controls having tPSA levels of 2.5 to 10 ng/ml. Results: We identified two loci that were associated with %fPSA at a genome-wide significance level (P-8). The first associated SNP was rs3213764 (P= 6.45×10-10), a nonsynonymous variant (K530R) in the ATF7IP gene at 12p13. This variant was also nominally associated with tPSA (P =.015). The second locus was rs1354774 (P = 1.25 × 10-12), near KLK2 at 19q13, which was not associated with tPSA levels, and is separate from the rs17632542 locus at KLK3 that was previously associated with tPSA levels and prostate cancer risk. Neither rs3213764 nor rs1354774 was associated with prostate cancer risk or aggressiveness. Conclusions: These findings demonstrate that genetic variants at ATF7IP and KLK2 contribute to the variance of %fPSA.

AB - Background: Percentage of free-to-total prostate-specific antigen (%fPSA) is an independent predictor of risk for prostate cancer among men with modestly elevated level of total PSA (tPSA) in blood. Physiological and pathological factors have been shown to influence the %fPSA value and diagnostic accuracy. Materials/Methods: To evaluate genetic determinants of %fPSA, we conducted a genome-wide association study of serum %fPSA by genotyping 642,584 single nucleotide polymorphisms (SNPs) in 3192 men of European ancestry, each with a tPSA level of 2.5 to 10 ng/ml, that were recruited in the REduction by DUtasteride of Prostate Cancer Events study. Single nucleotide polymorphisms (SNPs) with P <10-5 were further evaluated among the controls of a population-based case-control study in Sweden (2899 prostate cancer cases and 1722 male controls), including 464 controls having tPSA levels of 2.5 to 10 ng/ml. Results: We identified two loci that were associated with %fPSA at a genome-wide significance level (P-8). The first associated SNP was rs3213764 (P= 6.45×10-10), a nonsynonymous variant (K530R) in the ATF7IP gene at 12p13. This variant was also nominally associated with tPSA (P =.015). The second locus was rs1354774 (P = 1.25 × 10-12), near KLK2 at 19q13, which was not associated with tPSA levels, and is separate from the rs17632542 locus at KLK3 that was previously associated with tPSA levels and prostate cancer risk. Neither rs3213764 nor rs1354774 was associated with prostate cancer risk or aggressiveness. Conclusions: These findings demonstrate that genetic variants at ATF7IP and KLK2 contribute to the variance of %fPSA.

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