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BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

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

Authors: Jyotsna Batra, Christina M Nagle, Tracy O'Mara, Melanie Higgins, Ying Dong, Olivia L Tan, Felicity Lose, Lene Marie Skeie, Srilakshmi Srinivasan, Kelly L Bolton, Honglin Song, Susan J Ramus, Simon A Gayther, Paul DP Pharoah, Mary-Anne Kedda, Amanda B Spurdle, Judith A Clements

Published in: BMC Cancer | Issue 1/2011

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Abstract

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.
Appendix
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Metadata
Title
A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival
Authors
Jyotsna Batra
Christina M Nagle
Tracy O'Mara
Melanie Higgins
Ying Dong
Olivia L Tan
Felicity Lose
Lene Marie Skeie
Srilakshmi Srinivasan
Kelly L Bolton
Honglin Song
Susan J Ramus
Simon A Gayther
Paul DP Pharoah
Mary-Anne Kedda
Amanda B Spurdle
Judith A Clements
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-119

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