Risk factors for the occurrence of undifferentiated carcinoma of nasopharyngeal type: a case-control study.

INTRODUCTION: The incidence rate of nasopharyngeal carcinoma in Serbia is less than one per 100,000 citizens, which classifies it as a region with low incidence for this disease. OBJECTIVE: The aim of this study was to test some hypotheses of the risk factors for undifferentiated carcinoma of nasopharyngeal type (UCNT) in the low incidence population. METHODS: A case-control study was used for the research. The study included 45 cases with histopathological diagnosis of UCNT and 90 controls. Cases and the controls were individually matched by sex, age (+/- 3 years), and place of residence (city-village). Data were gathered about sociodemographic characteristics, occupational exposure to harmful agents, habits, diet, personal history, and family history. In the analysis of the data, conditional univariate and multivariate logistic regression analyses were applied. RESULTS: According to the results of multivariate logistic regression analysis UCNT was significantly positively associated with "passive smoking" of tobacco in the family during childhood, frequent consumption of industrially manufactured food additives for enhancing flavour and frequent consumption of white bread. UCNT was significantly negatively associated with frequent consumption of margarine, olive oil and cornbread. CONCLUSION: In our low incidence population, an independent risk factor for the occurrence of UCNT was "passive smoking" of tobacco in the family during childhood, use of industrially manufactured food with additives for enhancing flavour and consumption of white bread. Multicentric study enrolling a greater number of cases would be desirable.

[Radiotherapeutical chromosomal aberrations in laryngeal cancer patients]. / Radioterapijska ostecenja hromozoma kod karcinoma larinksa.

INTRODUCTION: The authors present the results of cytogenetic analysis of 21 patients with laryngeal carcinomas diagnosed and treated in the period 1995-2000 at the Institute of Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia and Clinical Center of Novi Sad. MATERIAL AND METHODS: The patients were specially monitored and the material was analyzed at the Institute of Human Genetics of the School of Medicine in Belgrade as well as in the Laboratory for Radiological Protection of the Institute of Occupational and Radiological Health "Dr Dragomir Karajovic" in Belgrade. RESULTS: The incidence of chromosomal aberrations and incidence of exchange of material between sister chromatids were observed in the preparation of the metaphasic lymphocyte chromosomes of the peripheral blood obtained in the culture. Structural aberrations were found on the chromosomes in the form of breakups, rings, translocations and dicentrics as early as after a single exposure of patients to tumor radiation dose of 2 Gy in the field sized 5x7. Out of the total number of 35 cultivated blood samples obtained from 13 patients, 21 were successfully cultivated and they were proved to contain chromosomal aberrations. Some of the peripheral blood samples failed to show cell growth in vitro due to the lethal cell damages in vivo. DISCUSSION: We have concluded that the number of structural aberrations cannot be used as a biological measure of the absorbed ionizing radiation dose. The presence of aberrations per se is indicative of the mutagenic effect of the ionizing radiation, which was also confirmed in our series on the original model by cultivation of the peripheral blood lymphocytes in the culture of the cells of the volunteer donors upon in vitro radiation. Using the method of bromdeoxyuridylreductase, the increased incidence of SCE as a mutagenic effect was registered. CONCLUSION: It has been concluded that the increase of absorbed radiation dose in vitro leads to prolonged duration of cell cycle in the same conditions, which proves cytostatic effect of radiation. Further fundamental studies are required for clinical implementation of the findings.

Incidence of nasopharyngeal carcinoma in Belgrade during the period 1991-2005.

BACKGROUND/AIM: Nasopharyngeal carcinoma (NPC) is a relatively rare malignant disease, of which 80,000 individuals become ill around the world annually, which amounts to 0.7% of all carcinomas. The aim of this descriptive study was to analyze NPC incidence in Belgrade (the capital city of Serbia, with about 1.6 milion inhabitants) during the period 1991-2005. METHODS: In data analysis, crude rates age and sex specific rates, and standardized incidence rates were used. Standardization was performed by a direct method, using world population as the standard. RESULTS: In Belgrade, during the observed 15-year-period, the number of new NPC patients totaled 118, of which 86 (72.9%) were male and 32 (27.1%) were female. The average standardized incidence rate for men was 0.52 per 100,000 and for women 0.16 per 100,000. In both sexes the incidence was very low before 40 years of age. In men, the greatest incidence rate of NPC was in the 50-59 years age group, and in women in those 60 and more years old. Furthermore, undifferentiated carcinoma of nasopharyngeal type was 3.6 times more often in comparison to squamous cell carcinoma. CONCLUSION: Belgrade belongs to a region with a low incidence rate of NPC. Further investigations are needed to explain higher frequency of undifferentiated carcinoma of nasopharyngeal type than squamous cell carcinoma.

Head-neck cancer drug therapy--could it be improved?

Head-neck cancer is an area requiring more attention to a highly demanding therapy which has not been fully developed yet. Despite advances in diagnosis and treatment, including improvements of surgical techniques, radio- and chemotherapy and prevention strategies, the survival rates of patients with recurrent head-neck cancer are low. New drugs, including those targeting the epidermal growth factor receptor, p53 gene, RAS protein post-translation modification, the proteosome, vascular endothelial growth factor, cyclooxigenase-2 and other molecular pathways, are promising agents for management of head-neck cancer. Their potential is being tested in various settings, including chemoprevention, recurrent and metastatic disease and combination with radiotherapy and/or cytotoxic agents. Cytotoxic drugs could produce better effects if administered locally--laser thermal cisplatin application. The metronomic low-dose chemotherapy will prove effective. The anticoagulant therapy undoubtedly has its place. The potential lies in sound ongoing academic clinical trial--biomarkers leading to maximally promising pharmacogenomic based therapy. Better comprehension of tumor biology and mechanisms of resistance is necessary as well as the institution of reliable assays for clinical use.

[Significance of confirming Epstein-Barr virus nuclear antibody as tumor marker].

BACKGROUND/AIM: Study of the association between Epstein-Barr virus (EBV) and the tumors of the nasopharynx renders an opportunity to introduce causal treatment Already have been proven the anti-EBV (anti-Epstein-Barr nucleus antigene) antibodies in the blood serum of the patients infected with EBV, while over 91% of the patients with nasopharyngeal malignant tumors also have a detectable anti-EBV marker. The aim of this research was to determine if there were anti-EBV antibodies in the serum of the patients with the already verified nasopharyngeal malignant tumors, and, if there were, to determine the quantitative ratio to the values in the serum of the healthy controls. METHODS: The study involved 74 individuals in the period from 1994-2001 divided into four groups: group A counting 11 patients with undifferentiated carcinome of nasopharyngeal type (UCNT); group B counting 25 patients with UCNT X-ray treated at least three years before the onset of the study; group C including 28 healthy subjecets (blood donors), and the group D with 10 patients with planocellular nasopharyngeal carcinoma. Serologic diagnostics of the patients serum was performed using the techniques of Reedman and Klein for the detection of anti-EBV antibodies in the serum. RESULTS: The presence of the statistically significantly higher values of the mean geometric titer (MGT) of the anti-EBNA antibodies was determined in 36 patients with histologically verified UCNT as compared with the control groups including 10 patients with planocellular carcinomas of the nasopharynx and 28 blood donors. Presented were anti-EBNA titers with 95% confidence interval for any participants according to the Hoo clinical classification of nasopharyngeal tumors, as well as according to the fact if they had been radiotreated within the previous three years. CONCLUSION: The results of this study confirm the conclusions of the recent literature on the possible etiopathogenesis of nasopharyngeal tumors and the use of viral anti-EBNA antibodies as viral markers in the diagnostics of UCNT diseases.

Case-control study of oropharyngeal cancer.

BACKGROUND: In order to test some hypotheses of risk factors for oropharyngeal cancer (neoplasm of base of tongue, palate and tonsils) matched case-control study was conducted in Belgrade, Serbia and Montenegro, during the period 1998-2000. METHODS: Study comprised 100 incidence cases with oropharyngeal cancer and 100 controls with some non-malignant diseases of head and neck. RESULTS: According to multivariate analysis, ever smoking, interaction between smoking and alcohol consumption, and occupational exposure to wood dust were found to be independent risk factors for oropharyngeal cancer (odds ratio-OR=5.10 95% confidence intervals-95% CI=1.70-15.27, OR=2.61 95% CI=1.54-4.41, and OR=4.16 95% CI=1.45-11.91, respectively). CONCLUSION: The results of the present study are in line with other authors' findings showing that smoking and alcohol consumption are the main risk factors for oropharyngeal cancer. The effect of occupational exposure to wood dust warrants further investigation.

[Possibility of the use of serological method for the determination of immunoglobuline A antibody against early antigene of Epstein-Barr virus as a marker in the diagnosis of nasopharyngeal tumors].

BACKGROUND/AIM: According to the data from immunological, biological and molecular researches, there is a close association between the undifferentiated carcinoma of nasopharyngeal type (UCNT) and Epstein-Barr virus (EBV). To use IgA EA antibody as a serological marker in our patients with nasopharyngeal carcinoma from a clinical viewpoint. METHODS: 91 patients were followed in the period from 1989-1998. In 11 of the patients the antibody titre serum for the early antigen of EBV virus were determinated before the treatement, and in 24 of the patients 3 years after the treatement. There were three control groups of patients: 20 voluntary blood donors, 26 patients with squamocellular laryngeal carcinoma, and 10 patients with squamocellular nasopharyngeal carcinoma. RESULTS: In the group of 11 patients with UCNT before the treatment, the value of anti-EA IgA titre was 31.09, and in the patients after the treatement anti-EA IgA antiody titre was 14.56. In the control groups of patients the results were: in the blood donors 5.00; in the group with the diagnosis of squamocellular laryngeal carcinoma, the titre was 5.00; in the patients with squamocellular nosopharyngeal carcinoma, the titre anti-EA IgA was 5.36. CONCLUSION: These results were statisticly highly significant (p < 0.01). Our research clearly showed that anti-EA IgA EBV marker could be useful in diagnosing, differential diagnosing and prognosing as well.