A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

J Batra; C M Nagle; T O'Mara; M Higgins; Y Dong; O L Tan; Felicity Lose; L M Skeie; S Srinivasan; K L Bolton; H Song; S J Ramus; S A Gayther; P D P Pharoah; M Kedda; A B Spurdle; J A Clements

doi:10.1186/1471-2407-11-119

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A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

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A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival

J Batra, C M Nagle, T O'Mara, M Higgins, Y Dong, O L Tan, Felicity Lose, L M Skeie, S Srinivasan, K L Bolton, …

BMC Cancer, Vol.11, 119

2011

DOI: https://doi.org/10.1186/1471-2407-11-119

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Abstract

Kallikrein 15 single nucleotide polymorphism

ovarian cancer

splice variants

Background: KLK15 over-expression is reported to be a significant predictor of reduced progression-free survival and overall survival in ovarian cancer. Our aim was to analyse the KLK15 gene for putative functional single nucleotide polymorphisms (SNPs) and assess the association of these and KLK15 HapMap tag SNPs with ovarian cancer survival.Results: In silico analysis was performed to identify KLK15 regulatory elements and to classify potentially functional SNPs in these regions. After SNP validation and identification by DNA sequencing of ovarian cancer cell lines and aggressive ovarian cancer patients, 9 SNPs were shortlisted and genotyped using the Sequenom iPLEX Mass Array platform in a cohort of Australian ovarian cancer patients (N = 319). In the Australian dataset we observed significantly worse survival for the KLK15 rs266851 SNP in a dominant model (Hazard Ratio (HR) 1.42, 95% CI 1.02-1.96). This association was observed in the same direction in two independent datasets, with a combined HR for the three studies of 1.16 (1.00-1.34). This SNP lies 15bp downstream of a novel exon and is predicted to be involved in mRNA splicing. The mutant allele is also predicted to abrogate an HSF-2 binding site.Conclusions: We provide evidence of association for the SNP rs266851 with ovarian cancer survival. Our results provide the impetus for downstream functional assays and additional independent validation studies to assess the role of KLK15 regulatory SNPs and KLK15 isoforms with alternative intracellular functional roles in ovarian cancer survival. © 2011 Batra et al; licensee BioMed Central Ltd.

Details

Title: A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival
Authors: J Batra (Author) - Queensland University of Technology
C M Nagle (Author) - Queensland Institute of Medical Research
T O'Mara (Author) - Queensland University of Technology
M Higgins (Author) - Queensland University of Technology
Y Dong (Author) - Queensland University of Technology
O L Tan (Author) - Queensland University of Technology
Felicity Lose (Author) - Queensland Institute of Medical Research
L M Skeie (Author) - Queensland University of Technology
S Srinivasan (Author) - Queensland University of Technology
K L Bolton (Author) - University of Cambridge, United Kingdom
H Song (Author) - University College London, United Kingdom
S J Ramus (Author) - University College London, United Kingdom
S A Gayther (Author) - University College London, United Kingdom
P D P Pharoah (Author) - University of Cambridge, United Kingdom
M Kedda (Author) - Queensland University of Technology
A B Spurdle (Author) - Queensland University of Technology
J A Clements (Author) - Queensland University of Technology
Publication details: BMC Cancer, Vol.11, 119; 11
Publisher: BioMed Central Ltd.
Date published: 2011
DOI: 10.1186/1471-2407-11-119
ISSN: 1471-2407
Copyright note: Copyright © 2011 Batra et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Organisation Unit: University of the Sunshine Coast, Queensland; Office of Research
Language: English
Record Identifier: 99450704402621
Output Type: Journal article

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