A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival
Batra, Jyotsna, Nagle, Christina , O'Mara, Tracy, Higgins, Melanie , Dong, Ying, Tan, Olivia, Lose, Felicity , Skeie, Lene , Srinivasan, Srilakshmi, Bolton, Kelly , Song, Honglin , Ramus, Susan , Gayther, Simon , Pharoah, Paul , Kedda, Mary-Anne, Spurdle, Amanda , & Clements, Judith (2011) A Kallikrein 15 (KLK15) single nucleotide polymorphism located close to a novel exon shows evidence of association with poor ovarian cancer survival. BMC Cancer, 11(119), pp. 1-11.
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.
Impact and interest:
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|Item Type:||Journal Article|
|Keywords:||Kallikrein 15 single nucleotide polymorphisms, ovarian cancer, splice variants|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health|
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||© 2011 Batra et al; licensee BioMed Central Ltd.|
|Copyright Statement:||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.|
|Deposited On:||19 Jul 2012 16:28|
|Last Modified:||09 Apr 2014 22:21|
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