Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness

Felicity Lose; J Batra; T O'Mara; P Fahey; L Marquart; R A Eeles; D F Easton; A A Al Olama; Z Kote-Jarai; M Guy; K Muir; A Lophatananon; A A Rahman; D E Neal; F C Hamdy; Jenny L Donovan; S Chambers; R A Gardiner; J F Aitken; J Yaxley; K Alexander; J A Clements; A B Spurdle; M A Kedda

doi:10.1016/j.urolonc.2011.05.011

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Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness

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Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness

Felicity Lose, J Batra, T O'Mara, P Fahey, L Marquart, R A Eeles, D F Easton, A A Al Olama, Z Kote-Jarai, M Guy, …

Urologic Oncology: Seminars and Original Investigations, Vol.31(5), pp.635-643

2013

DOI: https://doi.org/10.1016/j.urolonc.2011.05.011

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Abstract

The human tissue Kallikrein family consists of 15 genes with the majority shown to be differentially expressed in cancers and/or indicators of cancer prognosis. We sought to elucidate the role of common genetic variation in four of the Kallikrein genes, KLK5, KLK6, KLK12, and KLK13, in prostate cancer risk and tumor aggressiveness. Genotyping of all 22 tagging single nucleotide polymorphisms (tagSNPs) in the KLK5, KLK6, KLK12, and KLK13 genes was performed in approximately 1,000 prostate cancer cases and 1,300 male controls from Australia. Data from any positive results were also accessed for 1,844 cases and 1,886 controls from a previously published prostate cancer genome-wide association study set from the United Kingdom. For one SNP in KLK12, rs3865443, there was evidence for association with prostate cancer risk of similar direction and magnitude in the replication set to that seen in the Australian cohort. We conducted genotyping of a further 309 prostate cancer cases, and combined analyses revealed an increased risk of prostate cancer for carriers of the rare homozygous genotype for rs3865443 (OR 1.28, 95% CI 1.04-1.57; P = 0.018). No other tagSNPs in the KLK5, KLK6, and KLK13 genes were consistently associated with prostate cancer risk or tumor aggressiveness. Analysis of a combined sample of 3,153 cases and 3,199 controls revealed the KLK12 tagSNP rs3865443 to be marginally statistically significantly associated with risk of prostate cancer. Considering the total number of SNPs investigated in this study, this finding should be interpreted cautiously and requires additional validation from very large datasets such as those of the Prostate Cancer Association group to investigate cancer associated alterations (PRACTICAL) Consortium. © 2013 Elsevier Inc.

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Title: Common variation in Kallikrein genes KLK5, KLK6, KLK12, and KLK13 and risk of prostate cancer and tumor aggressiveness
Authors: Felicity Lose (Author) - Queensland Institute of Medical Research
J Batra (Author) - Queensland Institute of Medical Research
T O'Mara (Author) - Queensland Institute of Medical Research
P Fahey (Author) - Queensland Institute of Medical Research
L Marquart (Author) - Queensland Institute of Medical Research
R A Eeles (Author) - Institute of Cancer Research and Cancer Genetics Unit, United Kingdom
D F Easton (Author) - Cancer Research UK Genetic Epidemiology Unit, United Kingdom
A A Al Olama (Author) - Cancer Research UK Genetic Epidemiology Unit, United Kingdom
Z Kote-Jarai (Author) - Institute of Cancer Research and Cancer Genetics Unit, United Kingdom
M Guy (Author) - Institute of Cancer Research and Cancer Genetics Unit, United Kingdom
K Muir (Author) - Warwick University, United Kingdom
A Lophatananon (Author) - Warwick University, United Kingdom
A A Rahman (Author) - Liaquat University of Medical and Health Sciences, Pakistan
D E Neal (Author) - University of Cambridge, United Kingdom
F C Hamdy (Author) - John Radcliffe Hospital, United Kingdom
Jenny L Donovan (Author)
S Chambers (Author) - Cancer Council Queensland
R A Gardiner (Author) - University of Queensland
J F Aitken (Author) - Griffith University
J Yaxley (Author) - Brisbane Private Hospital
K Alexander (Author) - Queensland University of Technology
J A Clements (Author) - Queensland University of Technology
A B Spurdle (Author) - Queensland Institute of Medical Research
M A Kedda (Author) - Queensland University of Technology
Publication details: Urologic Oncology: Seminars and Original Investigations, Vol.31(5), pp.635-643
Publisher: Elsevier Inc.
Date published: 2013
DOI: 10.1016/j.urolonc.2011.05.011
ISSN: 1078-1439
Organisation Unit: University of the Sunshine Coast, Queensland; Office of Research
Language: English
Record Identifier: 99450573902621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Oncology; Urology & Nephrology

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