Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma

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

Fees, performance and risk of Islamic and conventional investment funds : A theoretical and empirical approach

Les fonds d'investissement islamiques et conventionnels se retrouvent dans la mesure où ils ont la même finalité. En revanche, à la différence des fonds conventionnels, les fonds islamiques se doivent d'investir conformément à un ensemble de règles de sélection. Cette thèse s'intéresse à élaborer un cadre d'analyse théorique et empirique permettant d'expliquer les frais de gestion, ainsi que la performance et le risque des fonds d'investissement. Ainsi, ce travail commence par élaborer une analyse théorique autour des contrats de partage des pertes et des profits (venture contracts) confrontés aux problèmes d'asymétrie d'information. Un modèle théorique, en présence de problème de sélection adverse entre le gérant et l'apporteur de fonds, montre que les degrés d'aversion au risque respectifs du gérant et de l'investisseur ont un impact sur la négociation des frais de gestion indexés sur la performance périodique du fonds (carried interest). Les conclusions de ce modèle nous incitent à expliquer empiriquement le choix des partenaires du fonds concernant les clauses de rémunération, la performance et le risque des fonds d'investissement. Pour ce faire, nous élaborons une base de données unique qui comporte un échantillon international de fonds islamiques et conventionnels regroupés par société de gestion. En distinguant les fonds islamiques des fonds conventionnels, le cadre légal, les conditions politiques et économiques expliquent leurs frais, leurs performances et leurs risques.Islamic and conventional investment funds have the same purpose. However, unlike conventional funds, Islamic funds offer different investment contracts and have to invest in accordance with a set of selection rules. This dissertation focuses on developing theoretical and empirical analysis framework to explain the fixed and performance fees, the performance and the risk of investment funds. Thus, we begin by developing a theoretical analysis about profit and loss-Sharing contracts (venture capital) that face agency problems. Based on this theoretical framework, a theoretical model, in the presence of adverse selection problem between the fund manager and the investor, shows that the risk aversions of the fund manager and the investor have respectively an impact on the periodic performance fees (carried interest) during the bargaining stage. The conclusions of this model lead us to empirically explain the terms of compensation and profit-Sharing, the performance and the risk of funds. To achieve our objective, we create a unique database that has an international sample of Islamic and conventional funds grouped by management company. By distinguishing between Islamic and conventional funds, the legal, political and economic conditions explain their fees, performance and risk

Combined effects of <it>IL-8 </it>and <it>CXCR2 </it>gene polymorphisms on breast cancer susceptibility and aggressiveness

Abstract Background Interleukin-8 (IL-8/CXCL-8) is a prototype of the ELR+CXC chemokines that play an important role in the promotion and progression of many human cancers including breast cancer. We have recently showed the implication of polymorphism (-251) T/A of IL-8 gene in the susceptibility and prognosis of breast carcinoma. IL-8 acts through its CXCR1 and CXCR2 receptors. CXCR2, expressed on the endothelial cells, is the receptor involved in mediating the angiogenic effects of ELR+CXC chemokines and in particular IL-8. In the current study, we investigated the susceptibility and prognostic implications of the genetic variation in CXCR2 in breast carcinoma. We also confirmed the implication of IL-8 (-251) T/A polymorphism in a larger cohort. Finally, we combined the IL-8 and CXCR2 variant alleles and analyzed their effects in breast cancer risk and prognosis. Methods We used the allele-specific polymerase chain reaction to characterize the variation of IL-8 and CXCR2 for 409 unrelated Tunisian patients with breast carcinoma and 301 healthy control subjects. To estimate the relative risks, Odds ratios and 95% confidence intervals were calculated using unconditional logistic regression after adjusting for the known risk factors for breast cancer. Associations of the genetic marker with the rates of breast carcinoma-specific overall survival and disease-free survival were assessed using univariate and multivariate analyses. Results A highly significant association was found between the homozygous CXCR2 (+ 1208) TT genotype (adjusted OR = 2.89; P = 0.008) and breast carcinoma. A significantly increased risk of breast carcinoma was associated with IL-8 (-251) A allele (adjusted OR = 1.86; P = 0.001). The presence of two higher risk genotypes (the TA and TT in IL-8, and the TT in CXCR2) significantly increased the risk of developing breast carcinoma (adjusted OR = 4.15; P = 0.0004). The CXCR2 (+ 1208) T allele manifested a significant association with an aggressive phenotype of breast carcinoma as defined by a large tumor size, a high histological grade, and auxiliary's lymph node metastasis. A significant association between the IL-8 (-251) A allele and the aggressive form of breast carcinoma was also found. Moreover, the presence of the IL-8 (-251) A and/or the CXCR2 (+ 1208) T allele showed a significant association with a decreased overall survival and disease-free survival in breast carcinoma patients. Conclusion Our results indicated that the polymorphisms in IL-8 and CXCR2 genes are associated with increased breast cancer risk, as well as disease progress, supporting our hypothesis for IL-8 and ELR+CXC chemokine receptor (CXCR2) involvement in breast cancer pathogenesis.</p

Natural infection of Ctenodactylus gundi by Leishmania major in Tunisia.

International audienceIncriminating new rodent species, as reservoir hosts of Leishmania parasites is crucial for understanding the transmission cycle of cutaneous leishmaniasis in Tunisia. Ctenodactylus (C.) gundi was previously described as extremely abundant in all Tunisian Leishmania (L.) tropica foci in south Tunisia besides its presence in L. major endemic area. The aim of this study was to detect Leishmania species parasites among C. gundi in two endemic regions in Tunisia: Sidi Bouzid and Tataouine. Total DNA was isolated from the spleens and the livers of 92C. gundi. Leishmaniasis clinical manifestations were detected among 11 rodents (12%). Leishmania parasites were detected in 30 (32.6%) rodents using direct exam method. Leishmania DNA was detected in 40 (43.5%) C. gundi by combining results among spleens and livers using ITS1-PCR. Positive samples were confirmed to be L. major except for only one specimen which was L. tropica. These results demonstrated, for the first time, the high natural infection rate of C. gundi with L. major parasites in Tunisia. Hence, C. gundi should be considered as potential reservoir host of Leishmania parasites causing cutaneous leishmaniasis in Tunisia

Contribution of BRCA1 5382insC mutation in triple negative breast cancer in Tunisia

Abstract Background Triple negative breast cancer (TNBC) has been classified as a disease subgroup defined by the lack of expression of estrogen and progesterone receptors as well as the absence of the human epidermal growth factor receptor-2 (HER2) overexpression. Germline mutations in the BRCA1 gene have been associated with TNBC. Approximately 70% of breast cancers arising in BRCA1 mutation carriers and up to 23% of breast cancers in BRCA2 carriers display a triple negative phenotype. However, the contribution and the frequency of BRCA1 mutations in individuals with TNBC, not specifically selected for age at diagnosis or enriched family history of breast/ovarian cancer, have not been investigated in the Tunisian population and are to be established. The aim of the present study was to assess the contribution and the prevalence of recurrent BRCA1 germline mutation (5382inC) in Tunisian women with TNBC unselected for family history or age at onset. Methods For BRCA1 5382inC mutation detection, the exon 20 coding region and exon–intron boundaries of BRCA1 was analyzed using direct DNA sequencing. A total of 33 DNA samples from Tunisian women diagnosed with TNBC and unselected for family history or age at onset were analyzed. Results The 5382inC mutation was identified in 2 out of 33 women with TNBC with an overall prevalence of 6% (2/33). The detection rate of the 5382inC mutation among TNBC women with family history of breast cancer was 25% (2/8). The two 5382inC mutation carriers were postmenopausal and diagnosed at the age of 50 and 57. When stratified by age, the frequency of BRCA1 mutation in patients diagnosed at age ≥ 50 years was 8.7% (2/23). Conclusions Our results confirm a noticeable contribution of BRCA1 5382inC mutation in TNBC development in Tunisia and further indicate that screening for 5382insC mutation in the BRCA1 gene is of interest in genetic testing in our population. Additionally, our data highlight that receptor triple negativity could be an effective selection criterion for BRCA1 genetic test in our population and should therefore be considered in genetic testing guidelines in Tunisia