Search

Objectives: There is growing evidence suggesting that IL-18 levels may affect individual to virus-associated neoplasia and that single nucleotide polymorphisms (SNPs) within the gene may influence its production. In this study we wanted to know whether IL-18 polymorphisms at positions -607 C/A and -137 G/A are associated with susceptibility and/or are markers of nasopharyngeal carcinoma (NPC) prognosis., Methods: Using the restriction fragment length polymerase chain reaction (RFLP-PCR), 163 Tunisian patients and 164 healthy controls were genotyped., Results: No significant association was found between each studied polymorphism and NPC. However, we noted that the -607 A allele, which is associated with lower IL-18 production, increased the risk of advanced tumor stages (OR=3.59; P=0.017) and that this risk was more pronounced among the older patient's age at onset (OR=3.85; P=0.012). Moreover, the significant difference in CA/GG haplotype frequency distribution between young and older patients supported the idea that NPC disease has biologically different features between age sub-groups., Conclusion: Functional IL-18 gene polymorphisms do not influence the susceptibility to NPC in Tunisians but may contribute to disease onset and aggressiveness.

Nasopharyngeal carcinoma (NPC) is a multifactorial disease. Cytokines driving the immune response seem to be disturbed in NPC patients. Since interleukin-10 (IL-10) is known to reduce the production of interferon-gamma (IFN-gamma), we supposed that genetic differences in IL-10 and IFN-gamma expression could be a mechanism by which NPC cells escape antitumour immune response. As the production of each cytokine is affected by the genetic background, we investigated the possible association between single nucleotide polymorphisms in genes of IL-10 and IFN-gamma with NPC. Different IL-10 -1082 G/A and IFN-gamma+874 Tau/Alpha genotypes were determined in 160 patients with nasopharyngeal carcinoma and 197 healthy controls. No association was found either for each SNP studied alone or for the combined analysis for both IL-10 and IFN-gamma polymorphisms among NPC patients in comparison with controls. Compared with individuals from high incidence countries, we noted huge significant differences in genotype distribution between individuals from low and intermediate NPC incidence countries. Polymorphisms of the IL-10 and IFN-gamma do not appear to be associated with NPC risk in the Tunisian population. Nevertheless, we strongly believe that the relationship between cytokines polymorphisms and NPC susceptibility deeply depends on the ethnicity.

Background: Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. This study investigated the susceptibility and prognostic implications of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene polymorphisms in breast carcinoma patients., Methods: The authors used polymerase chain reaction and restriction enzyme digestion to characterize the variation of the CYP2E1, CYP2C19, CYP2D6, mEH and NAT2 gene in a total of 560 unrelated subjects (246 controls and 314 patients)., Results: The mEH (C/C) mutant and the NAT2 slow acetylator genotypes were significantly associated with breast carcinoma risk (p = 0.02; p = 0.01, respectively). For NAT2 the association was more pronounced among postmenopausal patients (p = 0.006). A significant association was found between CYP2D6 (G/G) wild type and breast carcinoma risk only in postmenopausal patients (p = 0.04). Association studies of genetic markers with the rates of breast carcinoma specific overall survival (OVS) and the disease-free survival (DFS) revealed among all breast carcinoma patients no association to DFS but significant differences in OVS only with the mEH gene polymorphisms (p = 0.02). In addition, the mEH wild genotype showed a significant association with decreased OVS in patients with axillary lymph node-negative patients (p = 0.03) and with decreased DFS in patients with axillary lymph node-positive patients (p = 0.001). However, the NAT2 intermediate acetylator genotype was associated with decreased DFS in axillary lymph node-negative patients., Conclusion: The present study may prove that polymorphisms of some XME genes may predict the onset of breast carcinoma as well as survival after treatment.

North Africa is one of the major Nasopharyngeal Carcinoma (NPC) endemic regions. Specific food items unique to this area were implicated to be associated with NPC risk, but results were inconsistent. Here we have performed a large-scale case-control study in the Maghrebian population from Tunisia, Algeria and Morocco. From 2002 to 2005, interviews were conducted on 636 cases and 615 controls. Controls were hospitalized individuals from 15 non-cancer hospital departments, or friends and family members of non-NPC cancer subjects, matched by center, childhood household type (rural or urban), age and sex. Conditional logistic regression is used to evaluate the risk of factors. In results, consumption of rancid butter, rancid sheep fat and preserved meat not spicy (mainly quaddid) were associated with significantly increased risk of NPC, while consumption of cooked vegetables and industrial preserved fish was associated with reduced risk. Other foods such as fresh citrus fruits and spicy preserved meat (mainly osban) in childhood, industrial made olive condiments in adulthood, were marginally associated. In multivariate analyses, only rancid butter, rancid sheep fat and cooked vegetables were significantly associated with NPC. In regard to possible causative substances, our results implicate the involvement of butyric acid, a potential Epstein-Barr virus (EBV) activator.

Radiation-induced breast sarcoma is a late complication of radiation treatment. We report a case of an undifferentiated sarcoma occurring 8 years after breast conserving treatment, which required mastectomy taking pectoralis major.

Interleukin-8 (IL-8) is an angiogenic chemokine that plays a potent role in both development and progression of many human malignancies including nasopharyngeal carcinoma (NPC). In the present study, we evaluated the susceptibility and prognostic implications of the (-251) T/A genetic variation in IL-8 in NPC. We used the allele-specific polymerase chain reaction to characterize the variation of the IL-8 promoter region for 160 unrelated Tunisian patients with NPC and 169 healthy control subjects. There was a significant association between the homozygotes IL-8 (-251) AA genotype and nasopharyngeal carcinoma (OR = 2.46; P = 0.004). The presence of the IL-8 (-251) AA genotype was highly associated with elevated NPC risk for male patients. A significant association was demonstrated between the IL-8 (-251) AA genotype and the aggressive forms of NPC as defined by large tumor size, lymph node metastasis, and advanced stages. Moreover, the presence of the IL-8 (-251) AA genotype indicated a significant association with decreased overall survival. Our findings suggest that the IL-8 promoter polymorphism is associated with increased nasopharyngeal carcinoma risk, particularly in males, as well as disease progress, supporting our hypothesis for IL-8 involvement in NPC pathogenesis.

Background: Matrix metalloproteinases (MMPs) are proteolytic enzymes that play important roles in tumor invasion and metastasis by degrading extracellular matrix components. Genetic variations in promoter regions of MMP genes, affecting their expression, have been associated with susceptibility to cancers. The aim of this study was to investigate the susceptibility and prognostic implications of the MMP-1 (-1607) 1G/2G and MMP-9 (-1562) C/T polymorphisms in nasopharyngeal carcinomas., Methods: The variation of the MMP-1 and MMP-9 promoter regions in 174 patients with NPC and 171 healthy control subjects was investigated. Association of the clinico-pathologic parameters and the genetic markers with the rates of the nasopharyngeal carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses., Results: No association was found between genetic variation in MMP-9 and the risk of NPC occurrence. In contrast, a significantly increased risk of NPC was associated with the homozygous MMP-1 (-1607) 2G2G genotype (OR=2.27; p=0.02). A significant association was also found between the 2G2G genotype and the aggressive forms of NPC as defined by large tumor size (T3-T4), lymph node metastasis and advanced stages (III-IV) at the time of diagnosis. Moreover, an association was ascertained between the MMP-1 polymorphism and gender (OR=2.90; p=0.02). In univariate analysis, the MMP-1 (-1607) 2G allele showed a significant association with reduced disease-free survival for NPC patients (p=0.03)., Conclusions: The genetic variation in MMP-1 may represent a marker for the increased risk of nasopharyngeal carcinoma.

The high prevalence of nasopharyngeal cancer (NPC) in Southern Asia and Mediterranean Northern Africa suggests genetic predisposition among other factors. While Human Leukocyte Antigen (HLA) haplotypes have been conclusively associated with NPC predisposition in Asians, Northern African Maghrebians have been less intensely studied. However, low resolution serological methods identified weak positive associations with HLA-B5, B13 and B18 and a negative with HLA-B14. Using sequence based typing (SBT), we performed a direct comparison of HLA class I frequencies in a cohort of 136 Tunisian patients with NPC matched for gender, age and geographical residence to 148 normal Tunisians. The bimodal age distribution of NPC in Maghrebians was also taken into account. HLA frequencies in normal Tunisians were also compared with those of Northern Moroccan Berbers (ME) to evaluate whether the Tunisian population in this study could be considered representative of other Maghrebian populations. HLA-B14 and -Cw08 were negatively associated with NPC (odd ratio = 0.09 and 0.18 respectively, Fisher p(2)-value = 0.0001 and = 0.003). Moreover, positive associations were observed for HLA-B-18, -B51 (split of -B5) and -B57 (p(2)-value < 0.025 in all) confirming previous findings in Maghrebs. The HLA-B14/Cw*08 haplotype frequency (HF) was 0.007 in NPC patients compared to 0.057 in both Tunisian (OR = 0.12; p(2)-value = 0.001) and Moroccan controls. This study confirms several previous associations noted by serologic typing between HLA class I alleles and the prevalence of NPC in Maghrebians populations. In addition, we identified a putative haplotype rare in Tunisian patients with NPC that may serve as a genetic marker for further susceptibility studies.

To find out whether polymorphisms 333-Ile/Val and 637-Asp/Gly of the transporter part of the antigen processing 1 gene (TAP1) are associated with the development of nasopharyngeal carcinoma (NPC), we studied a total of 374 subjects (209 patients and 165 controls). We used the amplification refractory mutation system polymerase chain reaction (ARMS-PCR) method for analyzing the TAP1 gene polymorphisms. We found a significant difference between the patients and the controls in both the TAP1 codon 333 and codon 637 (P = 0.009 and P = 0.002, respectively). We also found that genotypes with the A allele were present in 206 patients with NPC and 155 controls (98.5 vs. 93.9%; P = 0.032; OR = 4.43) and that genotypes with the B allele were more often present in the control group (45 vs. 32%; P = 0.004; OR = 0.48), suggesting a significant positive association of the A allele with NPC risk and a protective role of the B allele. We have observed an association between the distribution of TAP1 alleles and the NPC patient's age at onset, compared with controls. These results back up the fact that the etiology of NPC in intermediate-risk countries is completely different in each peak of age prevalence and that each peak may possess its own particular oncogenic mechanism.

Purpose: Extra-central nervous system (extra-CNS) metastases are relatively unknown failure patterns in medulloblastoma. The aim of this study was to analyse epidemiological, clinical and aetiopathological aspects of these extra-CNS localisations., Patients and Methods: Extra-CNS metastases were retrospectively identified in patients treated in the department of radiation therapy at Salah-Azaïz institute (ISA) for medulloblastoma. These metastases were diagnosed as extra-CNS for all secondary localisations not related to other tumour aetiology. Aetiopathological aspects are discussed with a literature review., Results: Among 103 patients treated and followed-up in the department of radiation therapy of ISA from 1970 to 1992, 8 developed extra-CNS metastases (7.7%). Age at diagnosis of primitive tumour varied from 3 to 23 years. Sex ratio was 1. Primitive tumour treatment was: complete surgical resection in 4 patients with preoperative cerebrospinal fluid shunting in two, cerebrospinal axis irradiation in 7 patients and a cerebral-limited irradiation in 1. Two patients received chemotherapy for their initial treatment (systemic in one case and intrathecal in the other). The mean free-interval from diagnosis of primitive tumour to extra-CNS metastases was 23 months, varying from 8 to 53 months. These metastases were located in the liver (1 case), cervical lymph nodes (2 cases), bone marrow (1 case) and bone (2 cases). Two patients had multiple metastases: bone and bone marrow (in one), lung, pleura, cervical lymph node and bone localisations (in one). Treatment of these metastases was: chemotherapy in 5 cases, chemotherapy and radiation in one, radiation therapy in one and 2 patients were given only supportive care treatment. All patients died or are in progressive disease in less than one year from the diagnosis of extra-CNS metastases., Conclusion: Extra-CNS metastases are not rare and have a poor prognosis. The most commonly involved sites are bone, cervical lymph nodes and bone marrow. A complete work-up at initial diagnosis is recommended to screen early metastases. Literature review showed that histopathologic grading might help to identify groups at risk.

Loss of FAS (CD95) expression is a common feature of malignant transformation, which has been related to loss of epithelial cell differentiation and loss of sensitivity to apoptosis. We investigated the potential association between FAS promoter polymorphism and the genetic susceptibility to the Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma. The in vivo functional significance of the FAS polymorphism was investigated by assessing the correlation between FAS genotypes and the presence of autoantibodies to cytoskeleton and nuclear antigens frequently detected in nasopharyngeal carcinoma. We determined the FAS polymorphism distributions by RFLP-PCR in 170 patients with nasopharyngeal carcinoma and in 224 sex and age-matched controls. We used ELISA and the immunofluorescence analysis to characterize the presence of IgG autoantibodies to the cytoskeleton and nuclear proteins in patients' sera. A significantly increased risk of nasopharyngeal carcinoma was associated with heterozygote FAS-A/G (OR=2.00, P=0.001) and homozygote FAS-G/G (OR=3.19, P=0.0001) variants. The increased frequency of FAS-G/G genotype is correlated with the presence of anti-nuclear autoantibodies in patients with nasopharyngeal carcinoma (P=0.0298). Our results demonstrated that FAS promoter polymorphism was significantly associated with the nasopharyngeal carcinoma in Tunisians. The anti-nuclear autoantibodies induction was also found to be related to FAS polymorphism. The FAS promoter polymorphism associated not only with the increased risk of nasopharyngeal carcinoma in Tunisians but also with immune response deregulation observed in this cancer.

Background: Leptin (LEP) has been consistently associated with angiogenesis and tumor growth. Leptin exerts its physiological action through its specific receptor (LEPR). We have investigated whether genetic variations in LEP and LEPR have implications for susceptibility to and prognosis in breast carcinoma., Methods: We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the LEP and LEPR genes in 308 unrelated Tunisian patients with breast carcinoma and 222 healthy control subjects. Associations of the clinicopathologic parameters and these genetic markers with the rates of the breast carcinoma-specific overall survival (OVS) and the disease free survival (DFS) were assessed using univariate and multivariate analyses., Results: A significantly increased risk of breast carcinoma was associated with heterozygous LEP (-2548) GA (OR = 1.45; P = 0.04) and homozygous LEP (-2548) AA (OR = 3.17; P = 0.001) variants. A highly significant association was found between the heterozygous LEPR 223QR genotype (OR = 1.68; P = 0.007) or homozygous LEPR 223RR genotype (OR = 2.26; P = 0.001) and breast carcinoma. Moreover, the presence of the LEP (-2548) A allele showed a significant association with decreased disease-free survival in breast carcinoma patients, and the presence of the LEPR 223R allele showed a significant association with decreased overall survival., Conclusion: Our results indicated that the polymorphisms in LEP and LEPR genes are associated with increased breast cancer risk as well as disease progress, supporting our hypothesis for leptin involvement in cancer pathogenesis.

Objective: To evaluate locoregional recurrence rate of breast cancer, determine its anatomoclinical characteristies and discuss the available therapeutic alternatives., Patients and Methods: A retrospective study including 41 patients with LRR following modified radical mastectomy or conservative surgery of invasive breast carcinoma without metastasis, between January 1993 and December 2002., Results: 38 cases of LRR occurred after mastectomy and 3 cases after conservative surgery. LRR rate was 4.84%, mean follow-up 44.7 months. Mean age of patients was 45 years and LRR mean occurrence time-interval 22.4 months. Recurrence was parietal in 25 cases, mammary in 2 cases, and nodal in 14 cases. 18 patients had to be operated on., Conclusion: Prognosis of breast cancer depends on distant metastasis. LRR constitutes the second major risk liable to influence the overall prognosis.

Interleukin-8 (IL-8), a potent chemoattractant, has been demonstrated to contribute to human cancer progression through its potential functions as a mitogenic, angiogenic, and motogenic factor. We designed a broad study to investigate whether genetic variation in IL-8 has implications for susceptibility to and prognosis in breast carcinoma. We used the allele-specific polymerase chain reaction to characterize the variation of the IL-8 promoter region for 308 unrelated Tunisian patients with breast carcinoma and 236 healthy control subjects. Associations of the clinicopathologic parameters and the genetic marker with the rates of the breast carcinoma-specific overall survival and the disease-free survival were assessed using univariate and multivariate analyses. A significantly increased risk of breast carcinoma was associated with heterozygous IL-8 (-251) TA (OR=1.58, p=0.02) and homozygous IL-8 (-251) AA (OR=1.76, p=0.01) variants. A significant association between the IL-8 (-251) AA homozygous genotype and the aggressive phenotype of breast carcinoma as defined by the high histological grade, auxiliary's lymph node metastasis, and large tumor size was found. The IL-8 (-251) A allele manifested a significant association with decreased overall survival and disease-free survival for breast carcinoma patients. The polymorphism in the promoter region of the IL-8 gene may not only represent a marker for the increased risk of breast carcinoma but also predict the clinical outcome.

Objectives: Interleukin-1 (IL-1) and interleukin-6 (IL-6) are determining factors in the immune and inflammatory responses to tumors cells. Experimental data suggest that interleukin-1 and interleukin-6 play important roles in the development and progression of breast cancer. We designed a broad study to investigate the susceptibility and prognostic implications of the genetic variation in IL-1alpha, IL-1beta and IL-6 in breast carcinoma., Experimental Design: We used the polymerase chain reaction and restriction enzyme digestion to characterize the genetic variation of IL-1alpha, IL-1beta and IL-6 in 305, unrelated Tunisian patients with breast carcinoma and 200 healthy control subjects. Associations between the genetic markers and the clinicopathological parameters, the specific overall survival rate (OVS) of breast carcinoma and the disease free-survival rate (DFS) were assessed using univariate and multivariate analyses., Results: Both IL-6 (-597) GA and IL-6 (-174) GC heterozygous genotypes were found to be significantly associated with breast carcinoma (OR = 1.59, p = 0.024 and OR = 1.61, p = 0.022 respectively). A highly significant association was found between the (+3954) T allele of IL1-B gene and the aggressive phenotype of breast carcinoma as defined by the high histological grade, axillary lymph node metastasis and large tumor size. The IL-1alpha (-889) TT homozygous genotype showed a significant association with reduced disease-free survival and/or overall survival rate. The IL-1beta (+3954) TT, IL-6 (-597) GG and IL-6 (-174) GG homozygous genotypes were found to be associated with reduced DFS but not with overall survival., Conclusions: The polymorphisms in the promoter region of the IL-6 gene may represent a marker for the increased risk of breast carcinoma. Genetic variations in IL-1alpha, IL-1beta and IL-6 may predict the clinical outcome of breast carcinoma.

Objective: Recently, we showed the implication of the polymorphism in tumor necrosis factor-alpha (TNF-alpha) gene in the susceptibility and prognosis of breast carcinoma. TNF-alpha acts through its receptors: types I and II. The TNFRII, expressed on the haematopoietic cells, is the high affinity receptor involved in mediating the biological effects of TNF-alpha. We investigated the susceptibility and prognostic implications of the genetic variation in the TNFRII in breast carcinoma., Methods: We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNFRII gene in 300 unrelated Tunisian patients with breast carcinoma and 200 healthy control subjects. Associations of the genetic marker with the rates of the breast carcinoma-specific overall survival and the disease-free survival were assessed., Results: A significant association was found between TNFRII-196M/R heterozygous genotype and breast carcinoma (OR = 1.61; P = 0.02). This association was more significant in post-menopausal patients (OR = 2.41, P = 0.0001). The 196R-TNFRII allele showed a significant association with increased overall survival and disease-free survival in breast carcinoma patients., Conclusion: Genetic variation in TNFRII may predict the late onset of breast carcinoma, relapse and death for patients with breast carcinoma.

Nasopharyngeal carcinoma (NPC) represents an interesting model in the field of head and neck cancers. This cancer is rare in occidental countries (<1/100,000) and relatively moderate to highly frequent in the Mediterranean area and south-east Asia. This disease is linked to Epstein-Barr virus with a latent infection starting in the oropharyngeal epithelium and involving not only both epithelial tumor cells but also B lymphocytes. This viral infection represents the early phase of carcinogenesis where Latent Membrane Protein-1 has an important role via the terminal part of the BARF-1 gene. There are also various chromosomal alterations reported in NPC concerning the regions of chromosomes 3p, 9p, 11q, 13q, 14q et 16q detected essentially in areas of suppressors genes. Allelic and antigenic specificities of class II and II HLA seems to be associated to an increased risk of NPC different according to the incidence areas. Anti-EBV serology is suggestive of for NPC with an elevated level of IgA EA (early antigen) and VCA (viral capsid antigen). Cyfra 21 represents a promising serum marker for NPC with a 80% sensitivity. Radiotherapy remains the base of loco-regional treatment with a more frequent and systematic use of systemic chemotherapy (primary or concomitant) for high-risk-patients (T3-4 and N2-3 disease).

Objective: To collect second cancers occurring in the head and neck area after treatment by chemotherapy and/or radiotherapy for undifferentiated nasopharyngeal carcinoma in Tunisia., Patients and Methods: This is a retrospective study of patients developing second cancers after treatment for nasopharyngeal UCNT by radiotherapy and/or chemotherapy. To be retained in this study, second tumour had to be histologically different from the initial UCNT, localised in the irradiated area and occurring after a minimal delay of 3 years., Results: We collect 11 cases of second cancers occurring among 2346 patients treated from 1984 to 2001 in Tunisia (0.46%). Patients have been treated for nasopharyngeal UCNT mainly advanced T3-T4 (72%) or N2-N3 (63%). Median age was 20 years (11 to 48) with a sex-ratio of 0.3 (3 M/8 F). Treatment protocol included primary chemotherapy in 4 cases (adriamycin-cisplatin) or adjuvant (in 4) associated to the loco-regional irradiation at a mean dose of 72 Gy (70 to 75). Median delay of second cancer occurrence was 9 years (3 to 17). Tumors were epidermoid carcinomas in 4 cases, fibrosarcomas (2), osteosarcomas (2), glioblastoma (1) and basocellular carcinomas in 2. Second tumors have been treated by surgery alone in 4 cases and chemotherapy alone in 7 patients. No patient have been reirradiated. Median survival was 17 months, 4 patients died and 7 are still alive including 4 in complete remission (24+, 36, 36 and 48+ months) and 3 with progressing disease (8, 16 and 18 months)., Conclusion: Even very rare, second cancers after treatment for UCNT need to be detected and have a poor prognosis.

Introduction: - The induction of malignant diseases is one of the most concerning late effects of ionizing radiation. The topic of this study deals with skin tumors developed in the irradiated areas in children given X-ray therapy for tinea capitis., Material and Methods: - All patients with malignant tumors of the scalp referred to Salah Azaiz Institute between 1970 and 2001 have been questioned in order to determine if there had been a prior X-ray irradiation for tinea capitis, its modality, and its consequences. The first scalp irradiation goes back to 1922 and the last was performed in 1963., Results: - Ninety-eight patients with 150 radio-induced cancers of the scalp following irradiation for tinea capitis are reported (1.5 lesion per patient). The patients were irradiated in various hospitals and dispensaries throughout the country. Eighty-one patients (82%) had only one session of radiation. The average age at irradiation was 12 (+/-6) years, the latent period for radiation-induced skin cancers was 36 (+/-14) years. In 61 patients (62%), the scalp appeared normal and in 38% radiodermatitis was noted. Patient age at diagnosis of malignancy varied from 20 to 83 years with an average of 47 years. Basal cell carcinomas (125 cases) and spinocellular carcinomas (16 cases) were the most common, three other cases of annexial tumors, two malignant non-Hodgkin's lymphomas and four melanoma lesions are also present. Radiotherapy was used for the treatment of 74 patients (alone in 42 and associated with surgery in 32 patients); 14 patients had exclusive surgical excision., Conclusions: - Basal cell carcinomas are the most frequent tumors arising on chronic radiodermatitis. In spite of the long latency period, patients' young age at irradiation explained the occurrence of these cancers at a relatively young age. Literature review is suggesting recessive mutation of tumor-suppressor genes as the characteristic abnormality in radio-induced cancer.

Glutathione S-transferase Theta1 and Mu1 (GSTT1 and GSTM1) are involved in the metabolism and detoxification of a wide range of potential environmental carcinogens. Conversely, they contribute to tumour cell survival by detoxification of numerous products induced by cancer therapy. The authors designed a large study to investigate the susceptibility and prognostic implications of the GSTT1 and GSTM1 gene deletions in breast carcinoma. The authors used the polymerase chain reaction to characterise the variation of the GSTT1 and GSTM1 genes in 309 unrelated Tunisian patients with breast carcinoma and 242 healthy control subjects. Associations of the clinic-pathologic parameters and the genetic markers with the rates of the breast carcinoma specific overall survival (OVS) and the disease-free survival (DFS) were assessed using univariate and multivariate analyses. A significant association was found between gene deletion of GSTT1 and the risk of early onset of breast carcinoma (OR=1.60, P=0.02). The lack of GSTT1 gene deletion was significantly associated with poor clinical response to chemotherapy (OR=2.29, P=0.03). This association was significantly higher in patients with axillary's lymph node-negative breast carcinoma (OR=12.60, P=0.005). The null-GSTT1 genotype showed a significant association with increased DFS in this selected population of patients. This association was even higher in patients carrying both null-GSTT1 and -GSTM1 genotypes. The gene deletion of GSTs may predict not only the early onset of breast carcinoma but also the clinical response to chemotherapy and the recurrence-free survival for patients with lymph node-negative breast carcinoma.

Purpose: To collect second cancers in patients treated for Hodgkin disease (HD) during adolescence and young adulthood at Salah Azaïz Institute of Tunis., Methods and Patients: We consider as second cancer all tumours other than HD observed in patients after treatment for HD., Results: Twenty-five patients among 614 treated for HD between 1975 and 1991 developed 26 secondary tumours (4.2%). There were 17 males and eight females (sex ratio 2:1). Mean age at the diagnosis of HD was 32.5 years (12-56). HD was stage II (eight cases), stage III (14) and stage IV in three. The first treatment was combined chemotherapy and radiotherapy in 22 cases and only chemotherapy in three cases (stage IV). Radiotherapy was delivered with Cobalt 60 by large fields. Mean dose was 41.3 Gy (2 Gy/fraction in 21 and 3.3 in one). Chemotherapy was MOPP (13), MOPP and vinblastine (four), MOPP-ABVD (five), ABVD (two) and vinblastine only in one. Mean delay of second tumours was 114.5 months (40-276). There was five acute myeloid leukaemia, two digestive non-Hodgkin lymphomas, five nodal high-grade lymphomas, three breast cancers (one in man associated with thyroid cancer), five lung cancers (three non-small cell and two of small cell type), two gastric tumours and one rectal cancer, one synovialosarcoma of the knee and one malignant Schwannoma of the neck. Median survival was 12.5 months (2-48). Twenty-one patients died and four are still alive with 8, 12, 24 and 48 months of follow-up., Conclusion: Second cancer risk after treatment for HD is not low. Risk factors and preventive strategies are discussed.

Several studies have shown statistical evidence of association between nasopharyngeal carcinoma (NPC) and specific human leukocyte antigen (HLA) alleles and highlighted the presence of candidate genes for this cancer within or nearby the HLA. Given their chromosomal location within HLA and their determining role in the immune response to tumor cells, we designed a case-controlled study to investigate the potential association of the genetic variation of the tumor necrosis factor-alpha (TNF-alpha) and that of the heat shock protein 70-2 (HSP70-2) with NPC. We used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNF-alpha promoter region and that of the HSP70-2 gene in 140 Tunisian patients with primary NPC and 274 healthy control subjects. No association was found between genetic variations in TNF-alpha and the risk of NPC in Tunisians. In contrast, a significant relative risk of NPC was found associated with the HSP70-2 homozygous genotype (P2/P2) (OR=2.309; P=0.006). The P2/P2 genotype of the HSP70-2 gene may be a marker of increased risk of NPC in Tunisians.

Objective and Methods: The aim of our study was to report the epidemiologic, clinical, and biologic profiles of dermatomyositis (DM) associated with malignancy in patients from Tunisia. From January 1982 to January 2000, we collected retrospectively 20 case reports of DM associated with cancer from the different university hospital centers of Tunisia. Initial workup included anamnesis, clinical examination, cancer staging and classification, serum muscle enzymes (creatine phosphokinase, lactate dehydrogenase, aldolase, and transaminases), electromyography, and muscular biopsy. We calculated the median survival and mean value of all the variables. Comparisons of statistical tests were done with the Kruskal-Wallis test., Results: Among the 130 DM cases of our study, 20 were associated with cancer (15.38%). The mean age of our patients was 49.6 years and the sex ratio (female/male) was equal to 3. Cancers were mainly those of the breast (35%) and nasopharynx (25%). DM followed a paraneoplastic course in 90% of the cases. The profile of seric muscular enzymes showed a significant statistical difference (P =.05) between a group of patients with severe muscular weakness and a group with moderate muscle weakness only for creatine kinase. The median survival was 36.5 months after diagnosis of DM and 48.6 months after that of cancer. The 5-year actuarial survival was 38% as related to cancer and 16% as related to DM. Mortality was 45%, in 90% as a result of cancer., Conclusions: In our study, nasopharyngeal carcinoma represents the second cancer associated with DM, after breast neoplasm, demonstrating the frequency of these 2 cancers in our country. Despite our reduced number of study samples, our study also suggests a relationship between severe muscle weakness and high seric muscle enzymes.

Purpose: To review the radiotherapy department experience in treating primary spinal cord ependymomas (PSCE), analyse prognostic factors and provide treatment recommendations regarding literature review., Materials and Methods: Sixteen patients with PSCE received postoperative radiotherapy between 1972 and 1997. There were 10 male and 6 female patients with a mean age of 34 years (range 2-63). Surgery was gross total resection in 2 cases, subtotal resection in 9, biopsy in 4 and of unknown type in one patient. All patients were treated with radiotherapy to the craniospinal axis (4 cases), spinal cord (1 case) and to the site of primary tumour in 11 cases., Results: Five year-survival rate was 73%. Two patients had recurrent tumours within the primary site. Gender, extent of surgery and treatment field extent were not prognostic factors. Histologic type was the only variable predictive of outcome. Patients with myxopapillary type had a 5-year survival rate of 100% compared with 47% for those with other histology types., Conclusion: We conclude that aggressive surgery is not necessary in the management of PSCE, localised field radiotherapy is associated with favourable outcome, and tumour grade is an important prognostic factor.

Rectal cancer is a different entity compared to colon cancer due to its particular clinical therapeutic and treatment failure profile. Its anatomical situation explain the more higher frequency of loco-regional relapses compared to its colic counterpart. Adjuvant therapy of rectal cancer follow the progress obtained in colon cancer using adjuvant fluorouracil based chemotherapy and is also based on radiotherapy. This treatment is frequently used as primary to reduce tumoral volume, to improve the quality of surgery and to decrease the risk of local relapses. Doses fo 20-30 Gy seems to be the standard for bulky lesions and.

By far the highest incidence of the Epstein-Barr virus (EBV)-associated nasopharyngeal carcinomas in young subjects was found in North Africa, a region of intermediate risk for adults. We used the immunofluorescence analysis and ELISA to characterize the presence of IgG autoantibodies to the cytoskeleton and nuclear proteins in sera of 82 Tunisian patients with primary nasopharyngeal carcinoma and those of 82 healthy subjects. To assess the specificity of the sera autoreactivity, inhibition tests were carried out using free autoantigens. Analysis of sera autoreactivity in patients with nasopharyngeal carcinoma and in control subjects showed that 23% of the patients had serum reactivity against more than 1 autoantigen tested compared to 1.2% in the control group (p = 10(-4)). The most frequent auto reactivity in patient's sera was found with tubulin and nuclear proteins (19.5% and 22% respectively vs. 6.1% and 1.2% in controls). The IgG auto reactivity inhibition studies indicate that all autoantigens, except native DNA, showed low values of IC(50) (concentration of antigen causing 50% inhibition of the antibody binding) reflecting the high affinity of these IgG autoantibodies. When patients and controls were stratified according to their age, IgG autoantibodies to tubulin were found specifically associated with the young age onset of the nasopharyngeal carcinoma (age under 25 years). IgG auto reactivity comparison before and after cancer therapy showed that only anti-tubulin reactivity was significantly affected by treatment. Our results demonstrate that the autoantibodies to the cytoskeleton and nuclear proteins are associated with the nasopharyngeal carcinoma in Tunisians. The anti-tubulin IgG autoantibodies may represent a serologic marker for the nasopharyngeal carcinoma in children and adolescents Tunisians., (Copyright 2002 Wiley-Liss, Inc.)

Cancer of the breast represents in Tunisia and the most frequent female cancer in the world. Hormonotherapy is one of the main weapons of the medical treatment based on the blockage of hormonal action on the cellular growth. Endocrine therapy remains an essential part of treatment in both adjuvant and metastatic settings and is guided by the presence and degree of expression of estrogen receptor (ER) and progesterone receptor (PgR). Adjuvant 5-years tamoxifen (TAM) is still the standard therapy for postmenopausal ER and/or PgR positive women. In premenopausal women and in adjuvant setting, medical castration by LH-RH analogues plus Tamoxifen in addition to chemotherapy improve the prognosis. All these data arose from the successive meta-analyses done showing a benefit from hormonotherapy for patients with positive HR in term of survival, disease-free survival, loco-regional and distant relapse rate. In metastatic disease, the position of tamoxifen is presently in competition with the third generation antiaromatases that seems to be equally active as tamoxifen opening the way for its use for the future in adjuvant situations.

A prospective study was done to test the efficacy of 5-fluorouracil (topical and systemic) in multiple and unresectable histologically proven facial squamous cell carcinomas (SCC) secondary to XP. Twelve patients (7M/5F, mean age 19.8 years) with multiple facial SCC were treated between 1994 and 1997. 5-FU was used as a twice-a-day local application in the documented areas, by continuous infusion associated with cisplatin (2 patients) and short infusion combined with folic acid (3 patients). Evaluation was done by clinical examination every two months for topical therapy and after every cycle for systemic treatment. Median treatment duration was 12 months (2 to 36 months). Treatment was well tolerated excluding episodes of pruritus in the treated areas. We observed mainly superficial tumour regression followed by dryness and crusting. In 5 cases, we performed biopsies after treatment showing in one case an extensive fibrosis with absence of tumour. However in the remaining 4 cases, despite a superficial reduction of tumour and a reconstitution of the epidermis, viable and unmodified squamous cell carcinoma remained in the deeper dermis. In the 5 patients treated by systemic 5-FU, we observed 1 complete response and 3 partial responses. Despite a dissociation between a good cosmetic result and a relatively superficial effect, topical 5-FU represents a useful therapeutic option in multiple unresectable facial SCC in patients with XP. Systemic chemotherapy is recommended in the event of more extended or profound lesions.

Background: Tumor necrosis factor-alpha (TNF-alpha) and stress proteins (heat shock proteins) are determining factors in the immune response to tumor cells. The authors designated a large study to investigate the susceptibility and prognostic implications of the genetic variation in TNF-alpha and hsp70-2 in breast carcinoma., Methods: The authors used the polymerase chain reaction and restriction enzyme digestion to characterize the variation of the TNF-alpha promoter region and that of the hsp70-2 gene in 243 unrelated Tunisian patients with breast carcinoma and 174 healthy control subjects. Associations of the clinicopathologic parameters and the genetic markers with the rates of the breast carcinoma specific overall survival and the disease free survival (DFS) were assessed using univariate and multivariate analyses., Results: A highly significant association was found between TNF2 homozygous genotype and breast carcinoma (relative risk [RR], 4.44; P = 0.006). A high relative risk of breast carcinoma was found to be associated with one hsp70-2 homozygous genotype (P2/P2; RR, 7.12; P = 0.0001). The TNF2 homozygous genotype showed a significant association with reduced DFS and/or overall survival by univariate test. Conversely, P2-hsp70-2 homozygous genotype associated with increased overall survival but not with DFS. Multivariate analysis retained significance for TNF2 homozygous genotype as an independent prognostic indicator for both DFS (RR, 2.75; P = 0.01) and overall survival (RR, 4.08; P = 0.01)., Conclusions: Genetic variation in TNF-alpha and hsp70-2 may represent not only markers for the increased risk of breast carcinoma but also may predict the clinical outcome., (Copyright 2001 American Cancer Society.)

Between 1989 and 1996, 40 cases with acute leukemia (16 males and 24 females) were diagnosed in our institution. Median age was 65 years (range, 56-88 years). Leukocyte count was more than 30.109/l in 42% of cases. According to the French-American-British (FAB) criteria, 11 cases were classified lymphoblastic and 29 myeloblastic. Sixteen patients have received palliative treatment because of there age and there bad performance status. Only 24 patients have received curative treatment. Complete remission was achieved in 12 cases (50%), 5 cases (20%) failed to respond and 7 (30%) died during induction. Relapse was observed in 8 cases. The 2-year survival rate was 10% confirming the worse prognosis of the acute leukemia in elderly.

Purpose: Keloid scars are unsightly, especially when located on the face or bare zones. The purpose of this study was to evaluate the therapeutic results of intraoperative brachytherapy in the management of keloids., Material and Methods: This retrospective study was based on the study of 82 patients with keloids treated in Salah Azaiz Institute (Tunisia) between 1982 and 1994 (65 women and 17 men). The mean age of patients was 23.4 years (+/- 8.4). A total of 114 lesions have been treated with surgical resection and intraoperative brachytherapy using an iridium source placed under the surgical scar. The length of iridium was chosen with the result that the radioactive thread exceeded 5 mm on each side of the surgical scar. The iridium source was loaded less than six hours after resection. Average iridium activity was 1.5 +/- 0.3 mCi/cm. Average iridium length was 56.8 +/- 34 mm. The referred isodose chosen for the target volume included the surgical scar and a margin of 5 mm around the iridium source, which was placed under the surgical scar. The average administered dose was 20.4 Gy (+/- 3.2 Gy)., Results: The 2-year local control rate was 87% for the whole group of lesions treated (n = 114). Local control rate of keloids processed by resection and intraoperative brachytherapy as the first treatment (59 cases) was 96% at two years. This rate was better than the local control of lesions that had been previously treated with anterior surgical resection (84% in 55 cases). For the latter group, lesions treated with a dose of more than 20 Gy had better local control, but the difference was not statistically significant (87 vs. 65% at two years, P = 0.41)., Conclusion: Intraoperative brachytherapy is effective for improving local control of keloids and preventing a recurrence. A rigorous technique and an adequate dose according to previous surgical treatment allows very good results.

Background: Nasopharyngeal carcinoma is a common cancer in Tunisia with an estimated incidence of 1.8/100,000. The tumor shows a characteristic association with paraneoplastic syndromes., Case Reports: We report three cases of histologically proven dermatomyositis associated with nasopharyngeal carcinoma in patients aged 40, 24 and 65 years. In all cases, the course of the paraneoplastic syndrome ran parallel to the nasopharyngeal carcinoma., Discussion: Dermatomyositis is one of the numerous paraneoplastic syndromes associated with nasopharyngeal carcinoma. Systematic examination of the nasopharynx is required in case of dermatomyositis.

Sjögren's syndrome is characterized by an increased risk of developing non-Hodgkin's lymphoma. The lymphoma is most frequently extra-nodal, preferentially affecting the salivary gland: low-grade MALT lymphoma. Conversely, underlying Sjögren's syndrome has been recently identified by some authors in patients with non-Hodgkin's lymphoma. In the present report, we present three cases of Sjögren's syndrome disclosed by low-grade salivary gland MALT lymphoma. The patients were all women aged 33, 38 and 52 years. Extension work-up revealed nodal and bone marrow involvement in one case and no evidence of disseminated disease in the two others. Using the European criteria, all of our patients had certain Sjögren's syndrome. Labial salivary gland biopsy and immunopathological studies in newly diagnosed low-grade MALT lymphoma would be helpful in identifying the real frequency of this association.

Between 1989 and 1996, 21 cases with acute non lymphoblastic leukemia (11 males and 10 females) were diagnosed in our institution. Median age was 9 years (range, 2-15 years). Leukocyte count was more than 50,109/l in 47% of cases. According to the French-American-British (FAB) criteria, 7 cases were classified M1, 10 cases were classified M2, 1 classified M4Eo and 3 classified M5. All patients were treated with "7 + 3" protocol and complete remission was achieved in 17 cases (80%), 2 cases (10%) failed to respond and 2 (10%) died during induction. Relapse was observed in 15 cases. The 3-year survival rate was 20% and the relapse-free-survival rate was 12% confirming the worse prognosis of this leukemia when treated with standard chemotherapy.

Purpose: Fractionated total-body irradiation (HTBI) is considered to induce less toxicity to normal tissues and probably has the same efficacy as single-dose total-body irradiation (STBI) in patients with acute myeloid leukemia. We decided to determine whether this concept can be applied to a large number of patients with various hematologic malignancies using two dissimilar fractionation schedules., Patients and Methods: Between December 1986 and October 1994, 160 patients with various hematologic malignancies were randomized to receive either a 10-Gy dose of STBI or 14.85-Gy dose of HTBI., Results: One hundred forty-seven patients were assessable. The 8-year overall survival rate and cause-specific survival rate in the STBI group was 38% and 63.5%, respectively. Overall survival rate and cause-specific survival rate in the HTBI group was 45% and 77%, respectively. The incidence of interstitial pneumonitis was similar in both groups. However, the incidence of veno-occlusive disease (VOD) of the liver was significantly higher in the STBI group. In the multivariate analysis with overall survival as the end point, the female sex was an independent favorable prognostic factor. On the other hand, when cause-specific survival was considered as the end point, the multivariate analysis demonstrated that sex and TBI were independent prognostic factors., Conclusion: The efficacy of HTBI is probably higher than that of STBI. Both regimens induce similar toxicity with the exception of VOD of the liver, the incidence of which is significantly more pronounced in the STBI group.

Between 1989 and 1995, 42 cases with acute lymphoblastic leukemia (18 males and 24 females) were diagnosed in our institution. Median age was 38.5 years (range, 16-88 years). Leukocyte count was more than 30.10(9)/l in 54% of cases. According to the French-American-British (FAB) criteria, 67% were classified L1 and 33% L2. Sixteen patients were treated with 12LA80 protocol, 14 patients with LALA 85 protocol, 6 patients with LALA 87 protocol and 6 patients with EORTC protocol. Complete remission was achieved in 22 cases (52%), 8 cases (20%) failed to respond and 12 (28%) died during induction. Relapse was observed in 10 cases. The 4-year survival rate was 28% confirming the worse prognosis of this leukemia when treated with standard chemotherapy.

BRCA1 is a breast cancer susceptibility gene. Germline mutations in BRCA1 gene are found in 5 to 10% of breast cancer. The aim of this study is to screen the tunisian women with familial or sporadic breast cancer for BRCA1 gene mutations. The authors used the Protein Truncation Test (PTT) and DNA sequencing to detect BRCA1 gene mutations in 12 tunisian families with breast cancer and the Allele Specific Oligonucleotide-PCR (ASO-PCR) to detect the 185delAG and 1294del40 mutations in 150 tunisian women with sporadic breast cancer. A nonsens mutation was found, by PTT, in exon 11 of BRCA1 gene in one case of familial breast cancer. No mutation in the rest of exons was found by the DNA sequencing. The BRCA1 1294del40 mutation was found only in a patient with non familial breast cancer. The 185delAG mutation was absent in all cases of breast cancer. These data suggest that the germline mutation of BRCA1 is implicated in breast cancer in Tunisia and that the 185delAG mutation is absent in arab tunisian women.

This study has been realized to determine epidemiological profile and clinicopathologic aspect of breast cancer in Tunisia. We have counted and analyzed all cancers of the breast diagnosed in Tunisia with proof pathologic or to defect cytologic of malignancy, between first January 1994 and 31 December 1994. In the course of this year, 689 new cases of mammary cancers have been diagnosed at the women. The average patient age was 50.0 years, the incidence standardized on the age of the cancer of the breast in Tunisia was 16.7/100,000 women. The average size of the tumor was 49.5 mm (35.8 mm at patients processed in private clinics and 50.7 mm at patients processed in the public hospitals). According to TNM classification of 1988, 7.2% of tumors were classified T1, 48.9% T2, 18.5% T3, and 23.4% T4 (6.2% T4d and 16.1% T4b). 22.1% of tumors were M1. 3.3% were in situ carcinoma. For the infiltrants cancers, the grade II SBR has been the most frequent (53.6%). On the therapeutic plan, the conservative processing has been practiced only at 17.6% of patients. The cancer of the breast in Tunisia rest again relatively little frequent, and its clinic profile resides alarming. The inflammatory cancer notion of the breast (equal T4d) intimately linked to Tunisia overestimates probably the reality. Cancers that were classified "PEV" in many publications would be in reality only for most of locally evolved and neglected cancers.

Purpose: The aim of this retrospective study was to investigate therapeutic result of cutaneous lymphoma in Tunisia., Patients and Methods: Between January 1969 and June 1994, 100 patients with cutaneous lymphoma were referred either to Salah Azaiz Institute or the other University Hospitals of Tunisia. Fifty-one patients had epidermotropic lymphoma and 49 non-epidermotropic lesions. Eighty-seven patients received complete treatment. Puvatherapy and other local dermatologic treatments were used for early stage mycosis fungoïdes. Thirty-two patients benefited from radiotherapy, with curative dose in 28 cases. Chemotherapy including anthracyclin agents was used for high grade lymphoma. Thirteen patients had association of radiotherapy and chemotherapy., Results: Five-year survival rates were 50% for patients with epidermotropic lesions and 56% for patients with non-epidermotropic cutaneous lymphoma. Statistical study has not identified any significant prognosis factor., Conclusion: Radiotherapy and chemotherapy are both effective. Treatment should depend on stage and histologic type.

Nasopharyngeal carcinoma (NPC) is the primary cancer of the head and neck localisations in the Salah Azaiz Institute (Tunisia). From 1970 to 1987, 80 patients with histologically proven T4 N0 NPC, were treated with exclusive radiation (70-75 Gy to the primary lesion and 50-55 Gy to cervical lymph nodes). The T4 N0 represents 7% of all NPC and 16% of the T4 treated in our Institute. Ninety percent of the patients are over 20 years old with a mean age of 52 years. The sex-ratio was 4:1. Extension to the brain was observed in 55% of the cases. Local control was 70% at 2 months after the end of irradiation. The actuarial survival at 5 years was 47%. Distant metastasis represent 13% (30% of all NPC). The main failure of treatment was local recurrence. The T4 N0 is probably a particular entity concerning the age, the response to radiotherapy and the low rate of distant metastasis.