Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population

Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon–intron boundaries using direct sequencing. Six families were found to carry BRCA1 mutations with a prevalence of 37.5%. Four different deleterious mutations were detected. Three truncating mutations were previously described: c.798_799delTT (916 delTT), c.3331_3334delCAAG (3450 delCAAG), c.5266dupC (5382 insC) and one splice site mutation which seems to be specific to the Tunisian population: c.212 + 2insG (IVS5 + 2insG). We also identified 15 variants of unknown clinical significance. The c.798_799delTT mutation occurred at an 18% frequency and was shared by three apparently unrelated families. Analyzing five microsatellite markers in and flanking the BRCA1 locus showed a common haplotype associated with this mutation. This suggests that the c.798_799delTT mutation is a Tunisian founder mutation. Our findings indicate that the Tunisian population has a spectrum of prevalent BRCA1 mutations, some of which appear as recurrent and founding mutations

La valeur pronostique du PASS score dans la distinction entre phéochromocytome bénin et malin

International audienceBACKGROUND: Differentiating malignant from benign pheochromocytoma has been challenging when based on histologic features. This is due to the definition of malignant pheochromocytoma which are defined by the presence of metastases. A PASS score was developed and according to many authors, a PASS score> =4 identified potentially malignant tumors.AIM: To assess the prognostic value of PASS score in differentiating benign pheochromocytomas from malignant ones.METHODS: The records of 11 patients with tumors diagnosed as "pheochromocytoma" were identified from 1970 to 2010 in the files of the pathology, intern medicine and biochemistry departments of the Charles Nicolle hospital and Pasteur Institute. Receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic performance of PASS. The logistic model was developed using the 11 predictive variables. Its performance was evaluated by calculating the area under the ROC curve and comparing it with that of the PASS.RESULTS: In benign tumors, The PASS score was =4 in 6 cases. In malignant tumors, the PASS score was >=4 in both cases. According to the ROC curve analysis, a PASS equal or superior to 4 identifies malignant pheochromocytoma with a sensitivity of 50% and a specificity of 45%.CONCLUSION: I think that PASS score, despite its low sensitivity, may help to reserve the more aggressive treatment and narrow follow up for potentially malignant tumors. Widespread of this called score with complete clinical data will help to validate these findings and to add other prognostic factors of value that could be a part of this scaled score such as immunohistochemical findings.Prérequis : La distinction entre phéochromocytome bénin et malin peut se révéler délicate sur le plan morphologique. Cette difficulté découle de la définition même des phéochromocytomes malins dont le diagnostic repose sur la présence de métastases. Un score de PASS a été développé afin de contribuer à cette distinction. Un score de PASS >4 est corrélé à un haut potentiel de malignité.But: Etudier la valeur pronostique du score de PASS afin de différencier les phéochromocytomes bénins et les phéchromocytomes malins.méthodes: Nous rapportons une étude à propos de 11 patients présentant des phéochromocytomes diagnostiqués entre 1970 et 2010. Des courbes ROC ont été utilisées afin d’évaluer le potentiel diagnostique du score de PASS. Ce modèle logistique a été développé en utilisant 11 variables prédictives. Sa performance a été évaluée en calculant l’aire comprise sous la courbe ROC.résultats: Dans les tumeurs bénignes, le sore de PASS était <4 dans 3 cas et ≥4 dans 6 cas. Dans les tumeurs malignes, le score de PASS était ≥4 dans les 2 cas. L’analyse de la courbe ROC a permis d’établir qu’un score ≥ à 4 permettait d’identifier les phéochromocytomes malins avec une sensibilité de 50% et une spécificité de 45%.Conclusion: Le score de PASS peut contribuer au diagnostic des phéochromocytomes malins et ce malgré sa faible sensibilité.Cependant, ce score pourrait être enrichi par de nouveaux items tel que les données imunohistochimiques permettant ainsi d’améliorer sa sensibilité

3-(p-nitrophenyl)Coumarin derivatives: Synthesis, linear and nonlinear optical properties

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Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1

International audienceAims and background: Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians. Material and methods: Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P < 0.05 (compare 2, version 1.02). Results: The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P = 0.0027, RR = 18.27 (20.0061-915.28)). Conclusion: Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis

Transcutaneous canine breast cancer detection in Tunisia: a pilot study

Abstract Background Breast cancer in Tunisia is often diagnosed at a late stage with long delay in time to consultation and to diagnosis.The aim of this study is to estimate the sensitivity and specificity of the transcutaneous breast cancer detection by canine olfactionin Tunisian women and to identify the potential confounding factors. Methods This is a diagnostic case control study that took place from October 2021 to November 2022 in the Department of Medical Oncology at the University Hospital Farhat Hached of Sousse and in the security and training dog center located in Sousse (K9 Dog Center Security & Training). A two-year-old male Belgian Malinois was trained to detect breast cancer on skin secretion samples in compresses that had been worn overnight by women on their breast and then a double-blind testing was performed. There was no contact between women and the dog. From the mentioned responses of the dog, four parameters were calculated: sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV). Results Two hundred women were included in this trial: 100 breast cancer (BC) patients recruited from Farhat Hached University Hospital of Sousse and 100 healthy volunteers (HV).The calculated sensitivity was 84% (95% CI 78–89%) and the calculated specificity was 81% (95% CI 75–86%). The calculated predictive values were: PPV = 83,51% (95% CI 78,37–88,65%) and NPV = 81,55% (95% CI 76.17–86.93%). In the multivariate study, only four confounding factors of test’s sensitivity were retained: age (OR = 1.210 [95% CI = 1.085–1.349]; p = 0.001), history of diabetes(OR = 0.017 [95% CI = 0.001–0.228]; p = 0.002), sampling at hospital (OR = 0.010 [95% CI = 0.003–0.464]; p = 0.010) and testing during chemotherapy courses (OR = 0.034 [95% CI = 0.003–0.404]; p = 0.007).For test’s specificity, we retained the three following confounding factors: age (OR = 1,104 [95% CI = 1.021–1.195]; p = 0.014), history of benign mastopathy (OR = 0.243 [95% CI = 0.074–0.805]; p = 0.021)and history of arterial hypertension (OR = 0.194 [95% CI = 0.053–0.707]; p = 0.013). Conclusion This is a pilot study that opens new avenues in developing a reliable cancer diagnostic tool that integrates the dog's olfactory ability to detect breast cancer using a transcutaneous sampling method. It could be a pre-test to select patients who are eligible to a screening mammogram, especially in low-income countries where there is no national mammography screening program. Pactr.org identifier PACTR202201864472288, registration date 11/01/2022

Lack of association between the angiotensin-converting enzyme gene (I/D) polymorphism and diabetic nephropathy in Tunisian type 2 diabetic patients

International audienceObjective. The aim of the present study was to investigate whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with diabetic nephropathy and type 2 diabetes in the Tunisian population. Design. A case-control study was conducted among 141 unrelated type 2 diabetic patients with (90 patients) or without nephropathy (51 patients) and 103 non-diabetic controls with normal fasting blood glucose. Genotyping was performed using a nested polymerase chain reaction amplification in order to identify correctly heterozygous individuals. Results. The distribution of DD, ID and II genotypes did not significantly differ between type 2 diabetic patients with or without nephropathy (DD: 44%; ID: 46%; II: 10% vs. DD: 41%; ID: 47 %; II: 12%, respectively). There was also no significant statistical difference between the genotype distribution and allele frequencies of the (I/D) polymorphism in all type 2 diabetic subjects compared to non-diabetic controls with normal fasting blood glucose (DD: 43%; ID: 46%; II: 11% vs. DD: 37%; ID: 48%; II: 15%, respectively). Conclusions. In the present preliminary study, the (I/D) polymorphism within the ACE gene is likely not associated with diabetic nephropathy nor with type 2 diabetes in the Tunisian studied population

Evidence for Association of the E23K Variant of KCNJ11 Gene with Type 2 Diabetes in Tunisian Population: Population-Based Study and Meta-Analysis

Aims. Genetic association studies have reported the E23K variant of KCNJ11 gene to be associated with Type 2 diabetes. In Arab populations, only four studies have investigated the role of this variant. We aimed to replicate and validate the association between the E23K variant and Type 2 diabetes in Tunisian and Arab populations. Methods. We have performed a case-control association study including 250 Tunisian patients with Type 2 diabetes and 267 controls. Allelic association has also been evaluated by 2 meta-analyses including all population-based studies among Tunisians and Arabs (2 and 5 populations, resp.). Results. A significant association between the E23K variant and Type 2 diabetes was found (OR = 1.6, 95% CI = 1.14–2.27, and P=0.007). Furthermore, our meta-analysis has confirmed the significant role of the E23K variant in susceptibility of Type 2 diabetes in Tunisian and Arab populations (OR = 1.29, 95% CI = 1.15–1.46, and P<10-3 and OR = 1.33, 95% CI = 1.13–1.56, and P=0.001, resp.). Conclusion. Both case-control and meta-analyses results revealed the significant association between the E23K variant of KCNJ11 and Type 2 diabetes among Tunisians and Arabs