971PD - Functional -413 A > T polymorphism in HMOX1 gene is associated with the clinical outcome of ovarian cancer patients treated with paclitaxel/platinum...

Date 30 September 2012
Event ESMO Congress 2012
Session Gynecological cancers
Topics Ovarian Cancer
Translational Research
Presenter Lukasz Milewski
Authors L. Milewski1, Z. Dabrowska2, L. Bodnar1, A. Synowiec1, C. Szczylik1, J. Malejczyk2
  • 1Department Of Oncology, Military Institute of Medicine, 04-141 - Warsaw/PL
  • 2Department Of Histology, Medical University o Warsaw, 02004 - Warsaw/PL

Abstract

Introduction

Heme oxygenase 1 (HMOX1) is a key enzyme involved in the heme metabolism. HMOX1 expression may be induced by oxidative stress and cytokines, and there is increasing evidence that it may exert cytoprotective effects and facilitate survival and growth of some tumor cells. Aim: The aim of our study was to analyze whether clinical outcome of ovarian cancer patients subjected to standard therapeutic procedures may be associated with the functional -413A > T single nucleotide polymorphism (SNP) within the promoter of HMOX1 gene.

Methods

The study included 135 patients (median age, 54 years; 95% CI, 39-69) with stage I-IV epithelial ovarian cancer who underwent cytoreductive surgery followed by standard paclitaxel/platinum analogue chemotherapy. Patients DNA was routinely isolated from the peripheral blood and -413A > T SNP was genotyped using specific SNP Genotyping Assay (Applied Biosystems).

Results

The respective frequencies of -413A > T SNP AA, AT and TT genotypes within the patients' group were 34.1% (46/135), 46.7% (63/135) and 19.3% (26/135) and were similar to distribution within the general population control group. Kaplan-Meier analysis has revealed that AA genotype was associated with significantly longer progression free survival time. The median progression free survival time was 22.2 months in AA harboring patients and 14.5 months in patients with AT + TT genotype (p = 0.033 by log-rank test). AA genotype was also significantly associated with longer overall survival time. Three-year overall survival in AA and AT + TT group was 77.9% and 52.5%, respectively (p = 0.014).

Conclusions

The results of our study show for the first time that response to the first line treatment and clinical outcome of ovarian cancer patients with standard paclitaxel/platinum analogue chemotherapy might be associated with functional -413A > T SNP in the HMOX1 gene. This finding may be of practical importance for prognostication and may suggest that HMOX-1 is a potential target for a supportive clinical intervention.

Disclosure

All authors have declared no conflicts of interest.