Genetic association of the KLK4 locus with risk of prostate cancer.

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-mesenchyma...

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Autores principales:	Felicity Lose, Srilakshmi Srinivasan, Tracy O'Mara, Louise Marquart, Suzanne Chambers, Robert A Gardiner, Joanne F Aitken, Australian Prostate Cancer BioResource, Amanda B Spurdle, Jyotsna Batra, Judith A Clements
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/01315c51f5e34bb6845a35b919654b57
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spelling	oai:doaj.org-article:01315c51f5e34bb6845a35b919654b572021-11-18T07:06:18ZGenetic association of the KLK4 locus with risk of prostate cancer.1932-620310.1371/journal.pone.0044520https://doaj.org/article/01315c51f5e34bb6845a35b919654b572012-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0044520https://doaj.org/toc/1932-6203The 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 P(trend)<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 (r(2) ≥ 0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.Felicity LoseSrilakshmi SrinivasanTracy O'MaraLouise MarquartSuzanne ChambersRobert A GardinerJoanne F AitkenAustralian Prostate Cancer BioResourceAmanda B SpurdleJyotsna BatraJudith A ClementsPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44520 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Felicity Lose Srilakshmi Srinivasan Tracy O'Mara Louise Marquart Suzanne Chambers Robert A Gardiner Joanne F Aitken Australian Prostate Cancer BioResource Amanda B Spurdle Jyotsna Batra Judith A Clements Genetic association of the KLK4 locus with risk of prostate cancer.
description	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 P(trend)<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 (r(2) ≥ 0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.
format	article
author	Felicity Lose Srilakshmi Srinivasan Tracy O'Mara Louise Marquart Suzanne Chambers Robert A Gardiner Joanne F Aitken Australian Prostate Cancer BioResource Amanda B Spurdle Jyotsna Batra Judith A Clements
author_facet	Felicity Lose Srilakshmi Srinivasan Tracy O'Mara Louise Marquart Suzanne Chambers Robert A Gardiner Joanne F Aitken Australian Prostate Cancer BioResource Amanda B Spurdle Jyotsna Batra Judith A Clements
author_sort	Felicity Lose
title	Genetic association of the KLK4 locus with risk of prostate cancer.
title_short	Genetic association of the KLK4 locus with risk of prostate cancer.
title_full	Genetic association of the KLK4 locus with risk of prostate cancer.
title_fullStr	Genetic association of the KLK4 locus with risk of prostate cancer.
title_full_unstemmed	Genetic association of the KLK4 locus with risk of prostate cancer.
title_sort	genetic association of the klk4 locus with risk of prostate cancer.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/01315c51f5e34bb6845a35b919654b57
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Genetic association of the KLK4 locus with risk of prostate cancer.

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