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Kallikrein-Related Peptidase 3 (KLK3/PSA) Single Nucleotide Polymorphisms and Ovarian Cancer Survival

Published online by Cambridge University Press:  21 February 2012

Tracy A. O'Mara ,
Christina M. Nagle ,
Jyotsna Batra ,
Mary-Anne Kedda ,
Judith A. Clements  and
Amanda B. Spurdle
Tracy A. O'Mara
Affiliation:
Hormone Dependent Cancer Program, Institute of Health and Biomedical Innovation, and Faculty of Science and Technology, Queensland University of Technology, Australia; Molecular Cancer Epidemiology Laboratory, Genetics and Population Health Division, Queensland Institute of Medical Research, Australia.
Christina M. Nagle*
Affiliation:
Gynaecological Cancer Group, Genetics and Population Health Division, Queensland Institute of Medical Research, Australia. Christina.Nagle@qimr.edu.au
Jyotsna Batra
Affiliation:
Hormone Dependent Cancer Program, Institute of Health and Biomedical Innovation, and Faculty of Science and Technology, Queensland University of Technology, Australia; Molecular Cancer Epidemiology Laboratory, Genetics and Population Health Division, Queensland Institute of Medical Research, Australia.
Mary-Anne Kedda
Affiliation:
Hormone Dependent Cancer Program, Institute of Health and Biomedical Innovation, and Faculty of Science and Technology, Queensland University of Technology, Australia.
Judith A. Clements
Affiliation:
Hormone Dependent Cancer Program, Institute of Health and Biomedical Innovation, and Faculty of Science and Technology, Queensland University of Technology, Australia.
Amanda B. Spurdle
Affiliation:
Molecular Cancer Epidemiology Laboratory, Genetics and Population Health Division, Queensland Institute of Medical Research, Australia.
*
*ADDRESS FOR CORRESPONDENCE: Christina Nagle, Gynaecological Cancer Group, Genetics and Population Health Division, Queensland Institute of Medical Research, 300 Herston Road, Herston, Qld, 4006, Australia.

Abstract

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There is substantial evidence suggesting a role for hormone-regulated kallikrein-related peptidases (KLKs) in carcinogenesis and tumour metastasis. KLKs are considered to have potential as prognostic biomarkers for hormone dependent cancers, particularly ovarian cancer. The purpose of this study was to evaluate the association between Kallikrein-related peptidase 3 (KLK3) gene single nucleotide polymorphisms (SNPs) located in hormone response elements and ovarian cancer survival. DNA samples were analyzed from 304 Australian women diagnosed with epithelial ovarian cancer. The KLK3 rs266882 and rs11084033 SNPs were genotyped by the Sequenom iPLEX Mass Array platform. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models. An association was observed with ovarian cancer survival for homozygote carriers of the rare allele of rs11084033 (adjusted HR 2.12, 95% CI 1.08–4.15). This finding is consistent with bioinformatic analysis predicting the rs11084033 rare allele to be responsible for the loss of a confirmed androgen response element, and with published expression data suggesting that aggressive ovarian cancers show decreased KLK3 tumor expression. The rs11084033 has potential prognostic significance in ovarian cancer. However, this finding requires replication, and further investigation regarding the functional significance of rs11084033 and correlated SNPs.

Keywords

kallikrein-related peptidase 3 SNPovarian cancersurvivalprognosishormone dependant cancers
Type
Articles
Information
Twin Research and Human Genetics , Volume 14 , Issue 4 , 01 August 2011 , pp. 323 - 327
Copyright
Copyright © Cambridge University Press 2011