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 place of work:
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 the journal:
Otorinolaryngol Foniatr, 56, 2007, No. 1, pp. 24-30.
Category:
Original Article
Summary
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
Zdroje
1. Arikan, S., Akcay, T., Konukoglu, D., Obek, C., Kural, A. R.: The relationship between antioxidant enzymes and bladder cancer. Neoplasma, 52, 2005, 4, s. 314-317.
2. Bhuvarahamurthy, V., Balasubramanian, N., Govindasamy, S.: Effect of radiotherapy and chemoradiotherapy on circulating antioxidant system of human uterine cervical carcinoma. Molecular and Cellular Biochemistry, 158, 1996, 1, s. 17-23.
3. Bier, H., Hoffamnn, T., Eickelmann, P., Hafner, D.: Chemosensitivity of head and neck squamous carcinoma cell lines is not primarily correlated with glutathione level but is modified by glutathione depletion. Journal of Cancer Research and Clinical Oncology, 122, 1996, 11, s. 653-658.
4. Bohn, S. K., Smeland, S., Sakhi, A. K.: Post-radiotherapy plasma total glutathione is associated to outcome in patients with head and neck squamous cell carcinoma. Cancer Letters, 18, 2, s. 240-247.
5. Genkinger, J. M., Platz, E. A., Hoffman, S. C.: C47T polymorhism in manganese superoxide dismutase, antioxidant intake and survival. Mechanisms of Ageing and Development, 127, 2006, 4, s. 371-377.
6. Hrizostov, D., Gadjeva, V., Vlaykova, T., Dimitrov, G.: Evaluation of oxidative stress in patients with cancer. Archives of Physiology and Biochemistry, 109, 2001, 4, s. 331-336
7. Chistyakov, D. A:, Savostanov, K. V., Zotova, E. V., Nosikov, V. V.: Polymorphisms in the Mn-SOD and EC-SOD genes and their relationship to diabetic neuropathy in type I diabetes mellitus. BMC Medical Genetics, 2, 2000, s. 4-10.
8. Jaloszynski, P., Jaruga, O., Olinski, R., Biczysko, W., Szyfter, W., Nagy, E. et al.: Oxidative DNA base modifications and polycyclic aromatic hydrocarbon DNA adducts in squamous cell carcinoma of larynx. Free Radicals Research, 37, 2003, 3, s. 231-240.
9. Kakko, S., Päivänsalo, M., Koistinen, P., Kesäniemi, Y. A., Kinnula, V. L., Savolainen, M. J.: The signal sequence polymorphism of the MnSOD gene is associated with the degree of carotid atherosclerosis. Atherosclerosis, 168, 2003, s. 47-152.
10. Kaynar, H., Meral, M., Turhan, H., Keles, M., Celik, G., Akcay, F.: Glutathione peroxidase, glutathione-S-transferase, catalase, xanthine oxidase, Cu-Zn superoxide dismutase activities, total glutathione, nitric oxide and malondialdehyde levels in erythrocytes of patients with small cell and non-small cell lung cancer. Cancer Letters, 227, 2005, 2, s. 133-139.
11. Khoschsorur, G. A., Winklhofer Roob, B. M., Rabl, H., Auer, T., Peng, Z., Schaur, R. J.: Evaluation of a senstitive HPLC method for the determination of malondialdehyde, and application of the method to different biological materials. Chromatographia, 52, 2000, s. 181-184.
12. Korotkina, R. N., Matskevitch, G. N., Devlikano, A. S., Vishnevskii, A. A., Kunitsyn, A. G., Karelin, A. A.: Activity of glutathione metabolizing and antioxidant enzymes in malignant and benign tumors of human lungs. Bulletin of experimental Biology and Medicine, 133, 2002, 6, s. 606-608.
13. Reznick, A. Z., Klein, I., Eiserich, J. P., Cross, C. E., Nagler, R. M.: Inhibition of oral peroxidase aktivity by cigaretce smoke: in vivo and in vitro studies. Free Radical Biology&Medicine, 34, 2003, 3, s. 377-384.
14. Sabitha, K. E., Shyamaladevi, C. S.: Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy. Oral Oncology, 35, 1999, s. 273-277.
15. Samir, M., el Kholy, N. M.: Thiobarbituric acid reactive substances in patients with laryngeal cancer. Clinical Otolaryngology and Allied Science, 24, 1999, 3, s. 232-234.
16. Seven, A., Civelek,S., Inci, E., Inci F., Korkut, N., Burcak, G.: Evaluation of oxidative stress parameters in blood of patients with laryngeal carcinoma. Clinical Biochemistry. 32, 1999, 5, s. 369-373.
17. Shimoda-Matsubayashi, S., Matsumine, H., Kobayashi, T., Nagakawa-Hatori, Y., Shimizu, Y., Mizino, Y.: Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. Biochemical and Biophysical Reserch Communications, 226, 1996, s. 561-565.
18. Subapriya, R., Kumaraguruparan, R., Ramachandran, C. R., Nagini, S.: Oxidant-antioxidant status in patients with oral squamous cell carcinomas at different inraoral sites. Clinical Biochemistry, 35, 2002, s. 489-493
19. Subapriya, R., Kumaraguruparan, R., Nagini, S., Thangavelu, A.: Oxidant-antioxidant status in oral precancer and oral cancer patients. Toxicology Mechanisms and Methods, 13, 2003, s. 77-81
20. Szuster-Ciesielska, A., Hryciuk-Umer, E., Stepulak, A., Kupisz, K., Kandefer, M.: Reactive oxygen species production by blood neutrophils of patients with laryngeal carcinoma and antioxidative enzyme activity in their blood. Acta Oncologica, 43, 2004, 3, s. 252-258.
21. Taysi, S., Uslu, C., Akcay, F., Sutbeyaz, M. Y.: Malondiadehyde and nitric oxide levels in the plasma of patients with advanced laryngeal cancer. Surgery Today, 33, 2003, 9, s. 651-654.
22. Yigitbasi, O. G., Guney, E., Haghighi, N., Dogan, P., Saraymen, R., Balkanli, S.: Oxidant and antioxidant status in larynx squamous cell carcinomas. Journal of Experimental and Clinical Cancer Research. 19, 2000, 4, s. 447-451.
Štítky
Audiology Paediatric ENT ENT (Otorhinolaryngology)Článok vyšiel v časopise
Otorhinolaryngology and Phoniatrics
2007 Číslo 1
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