Search

Epithelial Ovarian cancer (EOC) is the leading cause of death associated with gynecologic tumors. Because the disease is asymptomatic in early-stage, the majority of patients are not diagnosed until late stages, highlighting the need for the development of novel diagnostic biomarkers. Mediators of tumoral microenvironment may affect EOC progression and resistance to treatment.Analysis of serum proteins to identify a panel of theranostic biomarkers for EOC.Serum levels of 65 analytes were determined in EOC patients, and healthy controls with the ProcartaPlex Human Immune Monitoring 65-Plex Panel.Twenty-one analytes: 7 cytokines (IFN-γ, IL-12p70, IL-13, IL-18 and TSLP), 7 chemokines (Eotaxin, eotaxin-2, IP-10, BLC, I-TAC, SDF-1α, and fractalkine), 2 growth factors (MMP-1, VEGF-α), and 5 soluble receptors (APRIL, CD40L, TWEAK, CD30 and TNFRII; were significantly differentially expressed between the two groups. ROC curves showed that only seven of them (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine, and Tweak) had AUC values greater than 0.70 and thus had potential clinical utility. Moreover, five cytokines: IFN-γ, IL-1 β, IL-8, MIP-1β, and TNF-α are positively associated with patients who developed resistance to taxol-platinum-based chemotherapy (CT).This study has revealed a first panel of 7 analytes (IL-9, TNF-α, Eotaxin, IP-10, BLC, Fractalkine and Tweak) that can be used for early detection of EOC and a second panel of five cytokines (IFN-γ, IL-1β, IL-8, MIP-1β, TNF-α) that can help clinicians to identify EOC patients who are at higher risk to develop resistance to CT of EOC.

Background We evaluated the association of common VEGF-A SNPs as potential risk factors for laryngeal cancer (LC) and nasopharyngeal carcinoma (NPC) in Tunisians. Methods Study subjects comprised 73 NPC and 48 LC patients, along with 125 cancer-free control subjects. VEGF-A genotyping was done by the allelic discrimination method. Results Minor allele frequency (MAF) of the 8 tested VEGF-A SNPs was comparable between LC patients and controls. Significantly higher MAF of rs2010963 and rs833070 were seen in NPC patients compared to controls. Increased nasopharyngeal cancer risk was seen with both rs2010963 and rs833070 as heterozygous, and more so as homozygous states, thus establishing a dose-dependent effect. In addition, increased NPC risk was associated with rs833068 only in heterozygous state. Increased frequency of CCGAACTC haplotype was seen in LC cases than controls. This was in sharp contrast to NPC, where highly significant positive association was seen with ATCGGCCC, ATGAGCCC, CCCAGTCC, and CCGAACCC haplotypes, while ATCAACCC, ATGGACCC, CCCAGCCC, CCCAGCCT, and ATGGATCC haplotypes are protective factors for NPC. Conclusion VEGF-A SNPs are associated with altered risk of NPC, but not with LC, among Tunisian subjects.

A central role for advanced glycation end products (AGE) and their receptor (RAGE) in the pathogenesis of multiple cancer types, including colorectal cancer (CRC) was reported. We investigated the association between CRC and rs2853807, rs77170610, rs184003, rs1035798, rs2070600, rs1800684, rs1800624, and rs1800625 RAGE gene (AGER) polymorphic variants. Study subjects comprised 293 CRC patients [186 colon cancer (CC) and 107 rectal cancer (RC)] patients), and 264 age-, gender-, BMI-, and ethnicity-matched controls. Minor allele frequency (MAF) of rs77170610 and rs1800625 were significantly lower, while MAF of rs1035798 was significantly higher in CRC patients compared to control subjects, which was associated with reduced and increased risk of CRC, respectively; MAF of the remaining variants was comparable between CRC patients and controls. Significant difference in the distribution of rs2853807 and rs77170610 genotypes was seen between CRC patients and controls, with both variants associated with decreased risk of CRC. Comparison of the distribution of minor allele-carrying genotypes in CC and RC patient subgroups revealed lack of significant difference in the distribution of these genotypes between the patient subgroups. In view of the lack of LD between rs2853807 and rs77170610 with other variants, six-locus (rs184003, rs1035798, rs2070600, rs1800684, rs1800624, rs1800625) haplotypes were constructed. Haplotype analysis did not identify any specific 6-locus AGER haplotype associated with CRC. In conclusion, AGER gene rs2853807 and rs77170610 variants rs77170610 are associated with altered risk of CRC in Tunisians, but with no discrimination between CC and RC types.

Objectives The aim of this study was to investigate the role of IL-1β (−511C>T), TNFα (-308 G>A), IL-10 (-1082 G > A) and IL-1RN VNTR polymorphisms in the susceptibility to rheumatoid arthritis (RA) in Tunisians. Patients and methods Using PCR-based methods, 104 RA patients and 150 healthy controls were investigated. We compared allele and genotype frequencies in RA patients versus controls and analyzed their correlations with erosive form (EF). Results IL1-RN VNTR A1A3 genotype is associated with higher risk of RA ( P = 0.012, OR = 4.31). Among the cases, males who carry this genotype were more exposed to RA ( P = 0.044, OR = 8, 47). For IL1- β gene, a significantly higher frequency of the -511C/C genotype was observed in RA patients in comparison to controls ( P = 0.013, OR = 2.45). This higher frequency was especially observed in women ( P = 0,003, OR = 3.42). In contrast, IL10−1082G/G genotype was less common in patients ( P = 0.046, OR = 0.46). According to EF, men carrying IL1-RN VNTR A1A3 ( P = 0.005 OR = 5.28) and IL1-β−511C/C ( P = 0.015 OR = 2.61) genotypes develop non EF of RA. Moreover, TNFα-308 A allele ( P = 0.024, OR = 1.84) and A/A genotype ( P = 0.033, OR = 3.1) were positively associated to EF of RA. However, G allele ( P = 0.024, OR = 0.31) and GG genotype ( P = 0.31, OR = 0.031) of the TNFα-308 were protectors. Conclusion Our results indicated that IL-1RN VNTR, IL-1β (−511C>T) and IL-10 (-1082 G>A) are associated with susceptibility to RA, and that IL-1RN VNTR, IL-1β (−511C>T) and TNFα (-308 G>A) are associated with severity of RA.

The present study was undertaken to investigate the association between Hepatitis B Virus (HBV) infection and polymorphisms of tumour necrosis factor alpha TNF-α -308 G>A, TNF-α -238 G>A and TNF RII VNTR (p75) gene promoter in a Tunisian population. Blood samples were collected from 100 Tunisian patients with HBV infection, 45 with Chronic Hepatitis (CH), 36 with Liver Cirrhosis (LC), 15 with Hepatocellular Carcinoma (HCC) and 200 healthy individuals of similar ethnicity. Genomic DNA was extracted from peripheral blood leukocytes. Genotyping of the analysed polymorphisms was performed using Amplified Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR), Restriction Fragment Length Polymorphism (RFLP) and Variable Number Tandem Repeat PCR (PCR-VNTR). The variant homozygotes -308 GG were associated with 50% decreased risk of HBV chronic infection (GG vs AA+GA; p=0.010; OR=0.50; 95%CI=0.29-0.85). However, the carriers of minor allele -308 A have higher risk (1.5 times) to develop a chronic infection than other patients (p=0.027; OR=1.46; 95%CI=1.04-2.06). The minor allele of -238 polymorphism was positively associated with virus resistance and the development of chronic infection (p=0.043; OR=1.42; 95%CI =1.01 1.99). The distribution of -308, -238 and TNF RII VNTR (p75) among the three groups differed significantly. For HCC groups, there were statistically significant differences in allele distribution in -308, -238 respectively in which A allele remains a risk factor for HBV evolution to HCC (p=0.008 and p=0.026). Haplotype analysis revealed that TNF-α (-308A; -238A) was significantly associated to HBV chronic infection and moreover to disease aggravation to HCC stage. Our findings imply that variations in the genes governing the levels of constitutive and inducible TNF-α and TNF RII might be an important risk factor, which could explain the variable outcomes of HBV infection.

Objective We investigated the association between common vascular endothelial growth factor ( VEGF ) single nucleotide polymorphisms (SNPs) and the risk of cervical cancer (CC) in Tunisian patients and control women. Methods Study subjects comprised 86 CC cases and 124 control women. Genotyping of VEGF rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068, rs833070, rs3025039 SNPs was done by real-time PCR. Results Higher minor allele frequencies (MAF) of rs699947 (−2578C/A) [ P = 0.04; OR (95% CI) = 1.52 (1.02–2.29)], and rs1570360 (−1154G/A) [ P = 0.04; OR (95% CI) = 1.58 (1.01–2.47)] were seen in CC cases compared to control women. Marked differences in the distribution of rs699947 ( P = 9 × 10 −4 ) and rs1570360 ( P = 0.03) genotypes were seen between CC cases and control groups; the distribution of the remaining SNPs was comparable between CC cases and control women. The association of rs699947 and rs1570360 with heightened CC risk with was seen in the heterozygous, and more so in the homozygous states. Haploview analysis revealed high LD between rs699947, rs833061, rs1570360, rs2010963, rs25648, rs833068 and rs833070 but weak or no LD between rs3025039 and the other SNPs. Seven-locus (rs699947/rs833061/rs1570360/rs2010963/rs25648/rs833068/ rs833070) haploview analysis identified only CTGCCAG haplotype to be positively associated with CC [ P = 0.022; OR(95% CI) = 1.74 (1.08–2.79)]. Conclusion Specific VEGF variants (rs699947, rs1570360) and haplotype (CTGCCAG) may contribute to the development of CC among Tunisian women.