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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 LU orcid ; Kim, Seong-Tae ; Tao, Sha ; Gao, Zhengrong ; Young, Tracey ; Wiklund, Fredrik LU ; Feng, Junjie and Isaacs, William B. , et al. (2013) In Neoplasia 15(1). p.95-95
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... (More)
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 < 5 x 10(-8)). The first associated SNP was rs3213764 (P = 6.45 x 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 x 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Neoplasia
volume
15
issue
1
pages
95 - 95
publisher
Neoplasia Press
external identifiers
  • wos:000318618200009
  • scopus:84873047405
ISSN
1522-8002
DOI
10.1593/neo.121620
language
English
LU publication?
yes
id
3fc30045-25f4-41a8-8869-664fb8723f2b (old id 3821354)
alternative location
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556942/
date added to LUP
2016-04-01 11:04:16
date last changed
2024-03-10 14:31:13
@article{3fc30045-25f4-41a8-8869-664fb8723f2b,
  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 &lt; 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 &lt; 5 x 10(-8)). The first associated SNP was rs3213764 (P = 6.45 x 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 x 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       = {{Jin, Guangfu and Zheng, Siqun Lilly and Lilja, Hans and Kim, Seong-Tae and Tao, Sha and Gao, Zhengrong and Young, Tracey and Wiklund, Fredrik and Feng, Junjie and Isaacs, William B. and Rittmaster, Roger S. and Gronberg, Henrik and Condreay, Lynn D. and Sun, Jielin and Xu, Jianfeng}},
  issn         = {{1522-8002}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{95--95}},
  publisher    = {{Neoplasia Press}},
  series       = {{Neoplasia}},
  title        = {{Genome-wide Association Study Identifies Loci at ATF7IP and KLK2 Associated with Percentage of Circulating Free PSA}},
  url          = {{http://dx.doi.org/10.1593/neo.121620}},
  doi          = {{10.1593/neo.121620}},
  volume       = {{15}},
  year         = {{2013}},
}