Genetic Association of the KLK4 Locus with Risk of Prostate Cancer

Felicity Lose, Srilakshmi Srinivasan, Tracy O'Mara, Louise Marquart, Suzanne Chambers, Robert A. Gardiner, Joanne F. Aitken, Trina Yeadon, Pamela Saunders, Allison Eckert, Judith Clements, Peter Heathcote, Glenn Wood, Greg Malone, Hema Samaratunga, Angus Collins, Megan Turner, Kris Kerr, Amanda B. Spurdle, Jyotsna Batra & 1 others Judith A. Clements

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

LanguageEnglish
Article numbere44520
JournalPloS one
Volume7
Issue number9
DOIs
Publication statusPublished - 6 Sep 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Lose, F., Srinivasan, S., O'Mara, T., Marquart, L., Chambers, S., Gardiner, R. A., ... Clements, J. A. (2012). Genetic Association of the KLK4 Locus with Risk of Prostate Cancer. PloS one, 7(9), [e44520]. https://doi.org/10.1371/journal.pone.0044520
Lose, Felicity ; Srinivasan, Srilakshmi ; O'Mara, Tracy ; Marquart, Louise ; Chambers, Suzanne ; Gardiner, Robert A. ; Aitken, Joanne F. ; Yeadon, Trina ; Saunders, Pamela ; Eckert, Allison ; Clements, Judith ; Heathcote, Peter ; Wood, Glenn ; Malone, Greg ; Samaratunga, Hema ; Collins, Angus ; Turner, Megan ; Kerr, Kris ; Spurdle, Amanda B. ; Batra, Jyotsna ; Clements, Judith A. / Genetic Association of the KLK4 Locus with Risk of Prostate Cancer. In: PloS one. 2012 ; Vol. 7, No. 9.
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abstract = "The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.",
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Lose, F, Srinivasan, S, O'Mara, T, Marquart, L, Chambers, S, Gardiner, RA, Aitken, JF, Yeadon, T, Saunders, P, Eckert, A, Clements, J, Heathcote, P, Wood, G, Malone, G, Samaratunga, H, Collins, A, Turner, M, Kerr, K, Spurdle, AB, Batra, J & Clements, JA 2012, 'Genetic Association of the KLK4 Locus with Risk of Prostate Cancer', PloS one, vol. 7, no. 9, e44520. https://doi.org/10.1371/journal.pone.0044520

Genetic Association of the KLK4 Locus with Risk of Prostate Cancer. / Lose, Felicity; Srinivasan, Srilakshmi; O'Mara, Tracy; Marquart, Louise; Chambers, Suzanne; Gardiner, Robert A.; Aitken, Joanne F.; Yeadon, Trina; Saunders, Pamela; Eckert, Allison; Clements, Judith; Heathcote, Peter; Wood, Glenn; Malone, Greg; Samaratunga, Hema; Collins, Angus; Turner, Megan; Kerr, Kris; Spurdle, Amanda B.; Batra, Jyotsna; Clements, Judith A.

In: PloS one, Vol. 7, No. 9, e44520, 06.09.2012.

Research output: Contribution to journalArticle

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T1 - Genetic Association of the KLK4 Locus with Risk of Prostate Cancer

AU - Lose, Felicity

AU - Srinivasan, Srilakshmi

AU - O'Mara, Tracy

AU - Marquart, Louise

AU - Chambers, Suzanne

AU - Gardiner, Robert A.

AU - Aitken, Joanne F.

AU - Yeadon, Trina

AU - Saunders, Pamela

AU - Eckert, Allison

AU - Clements, Judith

AU - Heathcote, Peter

AU - Wood, Glenn

AU - Malone, Greg

AU - Samaratunga, Hema

AU - Collins, Angus

AU - Turner, Megan

AU - Kerr, Kris

AU - Spurdle, Amanda B.

AU - Batra, Jyotsna

AU - Clements, Judith A.

PY - 2012/9/6

Y1 - 2012/9/6

N2 - The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

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Lose F, Srinivasan S, O'Mara T, Marquart L, Chambers S, Gardiner RA et al. Genetic Association of the KLK4 Locus with Risk of Prostate Cancer. PloS one. 2012 Sep 6;7(9). e44520. https://doi.org/10.1371/journal.pone.0044520