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Role of Superoxide Dismutase in Spinocellular Carcinoma of Head and Neck - a Pilot Study


Authors: Richard Salzman 1;  R. Kostřica 1;  L. Pácal 2;  J. Tomandl 3;  K. Kaňková 2;  Z. Horáková 1
Authors‘ workplace: Klinika otorinolaryngologie a chirurgie hlavy a krku LF MU a FN u sv. Anny, Brno ;  přednosta prof. MUDr. R. Kostřica, CSc. 1;  Ústav patologické fyziologie a LF MU, Brno 2;  Biochemický ústav LF MU, Brno 3
Published in: Otorinolaryngol Foniatr, 56, 2007, No. 1, pp. 24-30.
Category: Original Article

Overview

Introduction:
Oxidative status plays an important role in cancer development. Our aim is to investigate relationship between genetic variants encoding for antioxidant enzymes; activity of the expressed enzyme and clinical stage of head and neck squamous cell carcinoma (HNSCC).

Material and Methods:
prospective study of 75 patients treated with head&neck squamous cell carcinoma at St. Anne’s University Hospital in Brno from July 2005 to August 2006. PCR-based methodology was used to detect genotype of the manganese superoxide dismutase (SOD) Ala16Val polymorphism. We measured activity of superoxide dismutase in plasma (p-SOD) and in erythrocytes (ery-SOD). Using high performance liquid chromatography we analyzed malondialdehyde (MDA) in plasma. Tumor necrosis factor (TNF) in plasma was measured by the ultrasensitive ELISA.

Results:
Our study revealed significantly lower p-SOD level in patients without metastatic spread to neck lymph nodes (n=30) in comparison to N+ patients (n=45, p=0.02, Mann-Whitney). Increased plasmatic MDA was found in patients with recurrent disease (n=13) in 22 months following complete remission (CR) when compared to those who remained in CR (n=58, remaining 4 patients didn’t reach CR, p=0.06, Mann-Whitney). Subjects with MDA < 0.25nmol/g manifested longer disease free interval than those with MDA > 0.25nmol/g (log rank test, p = 0.01). Patients with MDA level > 0.25nmol/g face 42.9% risk of recurrence in contrast to patients with MDA < 0.25nmol/g with a risk of 8.0% (p=0.01, χ² test). Furthermore, our study revealed that patients with p-SOD level < 1.3kU/g suffer from metastases in neck lymph nodes in 49.7% in contrast to 77.1% in those with p-SOD > 1.3kU/g (p=0.03, χ² test). Frequences of the Ala-9Val alleles were 58.8% Ala and 41.2% Val. Genotype distribution for the Ala/Val genetic polymorphism fits predictions for Hardy-Weinberg equilibrium (p=0.05, χ² test). Activities of p-SOD revealed significant differences when comparing groups representing different genetic variants of SOD polymorphism (p=0.05, Kruskal-Wallis). Otherwise, there were no significant associations between patient groups divided by locoregional metastatic spread to neck lymph nodes, patients in CR and those with recurrence or holders of different genetic variants of the Ala-9Val polymorphism. Neither alleles distribution showed differences when comparing afore-mentioned groups.

Conclusions:
Our results entitle us to hypothesize the important role of oxidative stress in head and neck oncology. Validation of our preliminary results could bring major changes to decision making in dealing with head and neck cancer. The coming research should focus on prognostication role of MDA in recurrent disease and value of SOD activity as a marker of metastatic potential

Key words:
oxidative stress, head and neck squamous cell carcinoma, superoxidedismutase, malondialdehyd, metastatic potential, prognostication factor


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Audiology Paediatric ENT ENT (Otorhinolaryngology)
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