A Single Nucleotide Polymorphism in Catalase Is Strongly Associated with Ovarian Cancer Survival.

Jimmy Belotte,Ghassan M Saed,Mohammed S Abusamaan,Mohammed G Saed,Gregory Dyson,Michael P Diamond,Nicole M Fletcher,Alvaro Galli

doi:10.1371/journal.pone.0135739

Abstract

Ovarian cancer is the deadliest of all gynecologic cancers. Recent evidence demonstrates an association between enzymatic activity altering single nucleotide polymorphisms (SNP) with human cancer susceptibility. We sought to evaluate the association of SNPs in key oxidant and antioxidant enzymes with increased risk and survival in epithelial ovarian cancer. Individuals (n = 143) recruited were divided into controls, (n = 94): healthy volunteers, (n = 18), high-risk BRCA1/2 negative (n = 53), high-risk BRCA1/2 positive (n = 23) and ovarian cancer cases (n = 49). DNA was subjected to TaqMan SNP genotype analysis for selected oxidant and antioxidant enzymes. Of the seven selected SNP studied, no association with ovarian cancer risk (Pearson Chi-square) was found. However, a catalase SNP was identified as a predictor of ovarian cancer survival by the Cox regression model. The presence of this SNP was associated with a higher likelihood of death (hazard ratio (HR) of 3.68 (95% confidence interval (CI): 1.149–11.836)) for ovarian cancer patients. Kaplan-Meier survival analysis demonstrated a significant median overall survival difference (108 versus 60 months, p<0.05) for those without the catalase SNP as compared to those with the SNP. Additionally, age at diagnosis greater than the median was found to be a significant predictor of death (HR of 2.78 (95% CI: 1.022–7.578)). This study indicates a strong association with the catalase SNP and survival of ovarian cancer patients, and thus may serve as a prognosticator.

Highlights

Epithelial ovarian cancer (EOC) accounts for 85 to 90% of all cancers of the ovaries, fallopian tubes and primary peritoneum; and displays various histologies such as serous, mucinous, or endometrioid [1]
We have reported the existence of a persistent pro-oxidant state in EOC that included increased expression of key prooxidant enzymes such as inducible nitric oxide synthase, NAD(P)H oxidase, and MPO [16,32,33]
We have determined that MPO can produce the nitrosonium cation (NO+) utilizing NO produced by inducible nitric oxide synthase (iNOS)

Summary

Introduction

Epithelial ovarian cancer (EOC) accounts for 85 to 90% of all cancers of the ovaries, fallopian tubes and primary peritoneum; and displays various histologies such as serous, mucinous, or endometrioid [1]. Ovarian cancer is the deadliest of all gynecologic cancers with an estimated. Association of a SNP in Catalase with Ovarian Cancer Survival. Treatment of ovarian cancer is performed with either cytoreductive surgery (CRS) followed by platinum/ taxane combination chemotherapy or neoadjuvant chemotherapy with interval CRS [3,4]. A 50–80% complete clinical response can be achieved in patients with advanced disease. Most treated patients will relapse within 18 months with chemoresistant disease [5]. While the chances of long-term patient survival are significantly increased when the cancer is detected at its early stage, to date, there is no reliable method available for early detection of this disease [5]

Objectives

Methods

Results

Conclusion