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Genome-wide Association Study Identifies Loci at ATF7IP and KLK2 Associated with Percentage of Circulating Free PSA

In English

Författare

  • 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
Visa allt

Summary, in English

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.

Publiceringsår

2013

Språk

Engelska

Sidor

95-95

Publikation/Tidskrift/Serie

Neoplasia

Volym

15

Issue

1

Dokumenttyp

Artikel i tidskrift

Förlag

Neoplasia Press

Ämne

  • Cancer and Oncology

Status

Published

Forskningsgrupp

  • Clinical Chemistry, Malmö
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Övrigt

  • ISSN: 1522-8002