Identification of two theranostic biomarker panels for epithelial ovarian cancer.

BACKGROUND: 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. AIM OF THE STUDY: Analysis of serum proteins to identify a panel of theranostic biomarkers for EOC. PATIENTS AND METHODS: Serum levels of 65 analytes were determined in EOC patients, and healthy controls with the ProcartaPlex Human Immune Monitoring 65-Plex Panel. RESULTS: 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 ß, IL-8, MIP-1ß, and TNF-α are positively associated with patients who developed resistance to taxol-platinum-based chemotherapy (CT). CONCLUSION: 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-1ß, IL-8, MIP-1ß, TNF-α) that can help clinicians to identify EOC patients who are at higher risk to develop resistance to CT of EOC.

Assessing serum cytokine profiles in inflammatory breast cancer patients using Luminex® technology.

BACKGROUND: Inflammatory breast cancer (IBC), accounts for the majority of deaths associated with breast tumors. Because this form is aggressive from its appearance and has a strong metastatic potential. The majority of patients are not diagnosed until late stages, highlighting the need for the development of novel diagnostic biomarkers. Immune mediators may affect IBC progression and metastasis installation. AIM OF THE STUDY: Analysis of serum proteins to identify a panel of prognostic biomarkers for IBC. PATIENTS AND METHODS: Serum levels of 65 analytes were determined in IBC and Non-IBC patients with the ProcartaPlex Human Immune Monitoring 65-Plex Panel. RESULTS: Fifteen analytes: 5 cytokines (IL-8, IL-16, IL-21, IL-22 and MIF), 7 chemokines (Eotaxin, eotaxin-3, Fractalkine, IP-10, MIP-1α, MIP-1ß and SDF-1α), One growth factors (FGF-2) and 2 soluble receptors (TNFRII and Tweak); were significantly differentially expressed between the two groups. ROC curves showed that twelve of them (IL-8, IL-16, IL-21, IL-22, MIF, MIP-1α, MIP-1ß, SDF-1α, TNFRII, FGF-2, Eotaxin-3, and Fractalkine) had AUC values greater than 0.70 and thus had potential clinical utility. Moreover, seven cytokines: IL-8, IL-16, MIF, Eotaxin-3, MIP-1α, MIP-1ß, and CD-30 are positively associated with patients who developed distant metastasis. Ten analytes: Eotaxin-3, Fractalkine, IL-16, IL-1α, IL-22, IL-8, MIF, MIP-1α, MIP-1ß, and TNFRII are positively associated with patients who had Lymph-Nodes invasion. CONCLUSION: This study has uncovered a set of 8 analytes (Eotaxin-3, Fractalkine, IL-16, IL-8, IL-22, MIF, MIP-1α, MIP-1ß) that can be used as biomarkers of IBC, and can be utilized for early detection of IBC, preventing metastasis and lymph-Nodes invasion.

Decreased risk of ovarian cancer associated with rs9898876 sex hormone-binding globulin gene variant.

BACKGROUND: Ovarian cancer (OC) is one of the most common gynecologic cancers,with significant morbidity and mortality. The risk of OC is influenced by hormone status, of which sex hormone-binding globulin (SHBG), which influences the serum availability of steroid sex hormones, is implicated in the pathogenesis and evolution of OC. The aim of this study is to evaluate the involvement of common SHBG gene variants in OC susceptibility and evolution. MATERIALS: A case control study including 71 OC patients and 74 cancer-free controls, who were genotyped for rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP. Genotyping was done by the allelic discrimination method, using VIC- and FAM-labeled primers. RESULTS: The minor allele frequencies of rs9898876, rs13894, rs1799941 and rs6257 SHBG SNP was comparable between OC cases and control women, implying no significant associations of the tested variants and overall OC risk. Taking homozygous wild-type genotype as reference (OR = 1.00), heterozygous rs9898876 (G/T), and minor allele-carrying genotypes [G/T + T/T] were associated with reduced risk of OC. While rs9898876 heterozygosity (G/T) was predictive of OC occurrence, no significant association of the remaining three tested SNPs was noted with altered risk of OC. Irrespective of FIGO staging, the four tested SHBG SNPs were not associated with the clinical progression of OC. CONCLUSIONS: In conclusion, SHBG rs9898876 is associated with a decreased risk of OC, and thus constitutes a potential diagnostic biomarker of OC.

Skin toxicity after Filgrastim treatment for an Ewing's sarcoma patient.

INTRODUCTION: Filgrastim is a granulocyte colony-stimulating factor (GSCF) used in some chemotherapy regimen to prevent febrile neutropenia. Most common reaction of filgrastim are aches and pain including headaches, nausea and skin rash. CASE REPORT: We report the case of a patient who developed unusual, non-commonly reported adverse toxidermy to filgrastim. At first the eruption was limited to the lower members and genetics organs. Then it slowly spread across the whole body presenting as a polymorphic exanthematous-pustulosis lesions. MANAGEMENT & OUTCOME: A cutaneous biopsy was done, identifying a toxidermy modified by systemic treatment. A pharmacological study linked the role of filgrastim to these lesions. After switching from filgrastim to lénograstim, his lesions are completely gone and haven't flared up again. Thus, clearly imputing the use of filgrastim. DISCUSSION: The cutaneous reaction that has reported with use of GSCF are sweet syndrome, erythema nodosum, pyoderma nodosum and pyoderma gangrenosum. As far as we know, no acute generalized exanthematous pustulosis due to GSCF has been reported.

Fecal Metabolic Profiling of Breast Cancer Patients during Neoadjuvant Chemotherapy Reveals Potential Biomarkers.

Breast cancer (BC) is the most common form of cancer among women worldwide. Despite the huge advancements in its treatment, the exact etiology of breast cancer still remains unresolved. There is an increasing interest in the role of the gut microbiome in modulating the anti-cancer therapeutic response. It seems that alteration of the microbiome-derived metabolome potentially promotes carcinogenesis. Taken together, metabolomics has arisen as a fascinating new omics field to screen promising metabolic biomarkers. In this study, fecal metabolite profiling was performed using NMR spectroscopy, to identify potential biomarker candidates that can predict response to neoadjuvant chemotherapy (NAC) for breast cancer. Metabolic profiles of feces from patients (n = 8) following chemotherapy treatment cycles were studied. Interestingly, amino acids were found to be upregulated, while lactate and fumaric acid were downregulated in patients under the second and third cycles compared with patients before treatment. Furthermore, short-chain fatty acids (SCFAs) were significantly differentiated between the studied groups. These results strongly suggest that chemotherapy treatment plays a key role in modulating the fecal metabolomic profile of BC patients. In conclusion, we demonstrate the feasibility of identifying specific fecal metabolic profiles reflecting biochemical changes that occur during the chemotherapy treatment. These data give an interesting insight that may complement and improve clinical tools for BC monitoring.

Risk factors for inflammatory and non-inflammatory breast cancer in North Africa.

PURPOSE: Studies of the etiology of inflammatory breast cancer (IBC), a rare but aggressive breast cancer, have been hampered by limited risk factor information. We extend previous studies by evaluating a broader range of risk factors. METHODS: Between 2009 and 2015, we conducted a case-control study of IBC at six centers in Egypt, Tunisia, and Morocco; enrolled were 267 IBC cases and for comparison 274 non-IBC cases and 275 controls, both matched on age and geographic area to the IBC cases. We administered questionnaires and collected anthropometric measurements for all study subjects. We used multiple imputation methods to account for missing values and calculated odds ratios (ORs) and 95% confidence intervals (CIs) using polytomous logistic regression comparing each of the two case groups to the controls, with statistical tests for the difference between the coefficients for the two case groups. RESULTS: After multivariable adjustment, a livebirth within the previous 2 years (OR 4.6; 95% CI 1.8 to 11.7) and diabetes (OR 1.8; 95% CI 1.1 to 3.0) were associated with increased risk of IBC, but not non-IBC (OR 0.9; 95% CI 0.3 to 2.5 and OR 0.9; 95% CI 0.5 to 1.6 for livebirth and diabetes, respectively). A family history of breast cancer, inflammatory-like breast problems, breast trauma, and low socioeconomic status were associated with increased risk of both tumor types. CONCLUSIONS: We identified novel risk factors for IBC and non-IBC, some of which preferentially increased risk of IBC compared to non-IBC. Upon confirmation, these findings could help illuminate the etiology and aid in prevention of this aggressive cancer.

KCNB1 gene polymorphisms and related indel as predictor biomarkers of treatment response for colorectal cancer - toward a personalized medicine.

The KCNB1 gene variants were differentially associated with cancers. However, their association with colorectal cancer has not yet been explored. We investigated the contribution of the KCNB1 gene variants rs3331, rs1051295, and indel (insertion/deletion) rs11468831 Polymorphism as predictors of the treatment response in colorectal cancer patients. A retrospective study, which involved 291 Tunisian colorectal cancer patients (aged 60.0 ± 13.1 years), who were stratified into responder and non-responder groups, according to TNM stages and their responsiveness to chemotherapy based on fluorouracil. KCNB1 genotyping was performed with amplification-refractory mutation system-polymerase chain reaction, and was confirmed by Sanger sequencing. Sex-specific response was found and colorectal cancer females are less likely to achieve a positive response during the chemotherapy strategy, compared to males. Weight and body mass index, tumor size, and tumor localization are considered as predictive factors to treatment responsiveness. Carriage of rs11468831 Ins allele was significantly associated with successful therapy achievement (p adjusted < 0.001). Stratification of colorectal cancer patients' response according to tumor localization and TNM stages reveals negative association of rs3331 Major allele to treatment response among the patients with advanced cancer stages (subgroup G2). The presence of rs3331 (homozygous minor) C/C genotype was positively associated with decline in carcino-embryonic antigen (p = 0.043) and CA19-9 (p = 0.014) serum levels. On the other hand, the presence of rs1051295 (homozygous minor) A/A genotype was correlated with marked decline in CA19-9 serum levels. KCNB1 haplotype did not reveal any association between haplotypes and treatment response. The results obtained suggest that gender-specific strategies for screening treatment and prevention protocols as well as KCNB1 variants may constitute an effective model for ongoing personalization medicine.

Western influenced lifestyle and Kv2.1 association as predicted biomarkers for Tunisian colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most diagnosed malignancy worldwide. The global burden is expected to increase along with ongoing westernized behaviors and lifestyle. The etiology of CRC remains elusive and most likely combines environmental and genetic factors. The Kv2.1 potassium channel encoded by KCNB1 plays a collection of roles in malignancy of cancer and may be a key factor of CRC susceptibility. Our study provides baseline association between Tunisian CRC and interactions between KCNB1 variants and lifestyle factors. METHODS: A case-control study involving 300 CRC patients, and 300 controls was conducted Patients were carefully phenotyped and followed till the end of study. KCNB1 genotyping was confirmed by Sanger sequencing. Bivariate and multivariable logistic regression analyses were used to assess the clinical status, lifestyle and study polymorphisms association with CRC. RESULTS: We noted significant gender association with CRC occurrence. Moreover, CRC risk increases with high meat and fat consumption, alcohol use and physical activity (PA). Carriage of rs1051296 A/G and both rs11468831 ins/del and del/del genotypes (p < 0.001) were significantly associated with CRC risk. Analysis according to gender reveals correlation of rs1051295 A/G, rs11468831 non ins/ins (p = 0.01) with CRC susceptibility regardless of patients' gender while rs3331 T/C (p = 0.012) was associated with females. Stratification study according to malignancy site; Rectal Cancer (RC) and Colon Cancer (CC), reveals increasing RC risk by gender and high meat and fat consumption, alcohol use and PA. However, additional association with high brine consumption was noted for CC. The rs1051295 A/G (p = 0.01) was associated with RC risk. Increased CC risk was associated with carriage of rs1051295 A/G, rs11168831 (del/del) and (ins/del) genotypes. CONCLUSION: The risk of CRC increases with modifiable factors by Western influences on Tunisian lifestyle such as alcohol use, high fat consumption and possibly inadequate intake of vegetables. In addition, KCNB1 polymorphisms also markedly influence CRC susceptibility. Our study establishes key elements of a baseline characterization of clinical state, Western influenced lifestyle and KCNB1 variants associated with Tunisian CRC.

A practical approach to the management of colorectal cancer during the COVID-19 crisis in the reference cancer treatment center in Tunisia.

COVID-19 is an exceptional public healthcare emergency that affected all countries. The corona virus pandemic has made the treatment of all cancers difficult. This international phenomenon represents an outbreak in medicine and this situation is a major issue for all patients, whether they are infected with the virus or not. Colorectal cancer is one of the most common malignant tumors of the digestive tract which needs special multidisciplinary care. Treatment modalities including chemotherapy and targeted therapies can weaken the immune system and then cause serious or lethal coronavirus infections. This document gives an idea about how we dealt to protect patients with colorectal cancer at Salah Azaiez Institute during COVID 19 pandemic.

Suggestion of Tunisia's medical oncologist in the management of breast cancer during COVID-19 pandemic.

Cancer patients are at higher risk to be infected with COVID-19 and to develop a more severe form. Breast cancer (BC) treatments, including chemotherapy (CT), targeted therapy and immunotherapy can weaken the immune system and possibly cause lung problems. For all these reasons Salah Azaiez Institute's department of Medical Oncology took drastic actions to protect patients. In this article we will discuss protocol adjustments taken during the COVID-19 pandemic for breast cancer patients.

Single nucleotide polymorphism of transforming growth factor-ß1 and interleukin-6 as risk factors for ovarian cancer.

INTRODUCTION: We investigated the association between common variants in TGF-ß1, IL-6 and the risk of ovarian cancer (OC) in Tunisian patients and control women. MATERIAL METHODS AND RESULTS: Study subjects comprised 71 OC cases and 74 control women. Genotyping of TGF-ß1 and IL-6 SNPs was done by real-time PCR. No differences were noted in the minor allele frequencies of the three TGF-ß1 SNPs between OC patients and controls. However, marked differences in the distribution of TGF-ß1 rs1800469 genotypes were seen between OC cases and controls (p < 0.001), with TGF-ß1 rs1800469 heterozygous (C/T) genotype being negatively associated with OC (OR [95% CI] = 0.24 [0.15-0.58]). The allelic and genotypic distributions at IL-6 polymorphisms showed a positive association between minor allele (G) at IL-6 rs1880242 variant (p = 0.0275; R [95% CI] = 1.88 [1.03-3.46]) and the occurrence of OC. In fact, the presence of T allele [G/T + T/T] decrease the risk of OC (p = 0.021; OR [95% CI] = 0.38 [0.17-0.88]). In addition, the Haploview analysis demonstrated high linkage disequilibrium (LD) between IL-6 SNPs and eight-locus haplotype analysis identified that GGAGGGGA and GGAGGGTA haplotypes are positively associated with OC risk. A negative association was shown between IL-6 haplotype (TGGGCCTA) and OC occurrence. CONCLUSIONS: Our results suggest that TGF-ß1 rs1800469, IL-6 rs1880242 variants and IL-6 haplotype (TGGGCCTA) have protective roles of OC risk. IL-6 haplotypes (GGAGGGGA and GGAGGGTA) increase OC susceptibility among Tunisian women.

Clinico-pathologic and mammographic characteristics of inflammatory and non-inflammatory breast cancer at six centers in North Africa.

PURPOSE: We describe the clinico-pathologic and mammographic characteristics of inflammatory breast cancer (IBC) and non-IBC cases enrolled in a case-control study. Because IBC is a clinico-pathologic entity with rapid appearance of erythema and other signs, its diagnosis is based on clinical observation and thus, by necessity, subjective. Therefore, we evaluate our cases by photographic review by outside expert clinicians and by degree of adherence to the two most recent definitions of IBC: the international expert panel consensus statement and American Joint Committee on Cancer (AJCC) 8th edition (we used the slightly less restrictive 7th edition definition for our study). METHODS: We enrolled 267 IBC and 274 age- and geographically matched non-IBC cases at 6 sites in Egypt, Tunisia, and Morocco in a case-control study of IBC conducted between 2009 and 2015. We collected clinico-pathologic and mammographic data and standardized medical photographs of the breast. RESULTS: We identified many differences between IBC and non-IBC cases: 54.5% versus 68.8% were estrogen receptor-positive, 39.9% versus 14.8% human epidermal growth factor receptor 2-positive, 91% versus 4% exhibited erythema, 63% versus 97% had a mass, and 57% versus 10% had mammographic evidence of skin thickening. Seventy-six percent of IBC cases adhered to the expert panel consensus statement and 36% to the AJCC definition; 86 percent were confirmed as IBC by either photographic review or adherence to the consensus statement. CONCLUSIONS: We successfully identified distinct groups of IBC and non-IBC cases. The reliability of IBC diagnosis would benefit from expert review of standardized medical photographs and associated clinical information.

Association of common IL-10 promoter gene variants with the susceptibility to head and neck cancer in Tunisia

Background/aim: We investigated the association of three IL-10 promoter single-nucleotide polymorphisms and altered IL-10 plasma levels with the risk of head and neck cancer (HNC). Materials and methods: Study subjects comprised 194 HNC patients [137 nasopharyngeal cancer (NPC) and 57 laryngeal cancer (LC)], and 263 healthy controls. Genotyping of rs1800896 (-1082A>G), rs1800871 (-819C>T), and rs1800872 (-592A>C) IL-10 variants was performed by real-time PCR; IL-10 levels were measured by enzyme amplified immuno sensitivity assay (EAISA). Results: Study subjects comprised 194 HNC patients [137 nasopharyngeal cancer (NPC) and 57 laryngeal cancer (LC)], and 263 healthy controls. Genotyping of rs1800896 (-1082A>G), rs1800871 (-819C>T), and rs1800872 (-592A>C) IL-10 variants was performed by real-time PCR; IL-10 levels were measured by enzyme amplified immuno sensitivity assay (EAISA). Conclusion: Our results demonstrate that IL-10-1082, IL-10-819, and IL-10-592 variants, and haplotypes GC and GT constitute biomarkers for early detection of HNC, especially NPC subtype. IL-10 -819T/C and TA haplotype may be used as biomarkers for early detection of LC.

Increased risks between TLR2 (-196 to -174 ins/del) and TLR3 1377C>T variants and head and neck cancers in Tunisia.

INTRODUCTION: Previous studies have highlighted the importance of polymorphisms of toll-like receptors (TLRs) in the pathogenesis of certain cancers, including head and neck cancers (HNC). AIM OF THE STUDY: The aim of this study was to evaluate the association of TLR2 (-196 to -174 ins/del) and TLR3 (1377 C>T) as potential risk factors for HNC in Tunisians. MATERIAL AND METHODS: A case-control study including 246 HNC patients (174 nasopharyngeal carcinoma - NPC and 72 laryngeal cancer - LC) and 250 healthy controls. Genotyping was done by using PCR and PCR-RFLP methods. RESULTS: Higher minor allele frequencies of TLR2 (-196 to -174 ins/del) and TLR3 1377 C>T polymorphisms were seen in HNC, NPC, and LC compared to controls. In addition, higher increased HNC, NPC, and LC risk was associated with TLR2 ins/del and TLR2 del/del genotypes (p < 0.0001). Positive association with HNC, NPC, and LC risk was seen with TLR2 del-containing genotypes (ins/del + del/del) (p < 0.0001). The T/T genotype of TLR3 is associated with HNC, NPC, and LC susceptibility (p < 0.0001). Positive association with HNC and NPC risk was seen with TLR3 T allele carriers (C/T + T/T) (p < 0.0001). Increased frequency of T-ins, C-del, and T-del haplotypes was revealed in HNC and NPC cases than healthy controls; however, T-del was significantly higher in LC cases. CONCLUSIONS: Our results demonstrate an increased risk of HNC, NPC, and LC with TLR2 ins/del, TLR2 del/del, and TLR3 T/T genotypes. And positive association with T-ins, C-del, and T-del haplotypes with HNC and NPC and T-del haplotype with LC.

Association of interleukin-17A polymorphisms with the risk of colorectal cancer: A case-control study.

BACKGROUND: Interleukin (IL)-17A is proinflammatory cytokine produced by Th17 cells, which play key, but sometimes inconsistent role in autoimmunity and cancer. Polymorphic variants in IL-17A gene were differentially associated with susceptibility to cancer, including colorectal cancer (CRC). AIM: We investigated the association between six IL-17A gene variants (rs3819024, rs2275913, rs3819025, rs10484879, rs7747909, and rs3748067) with CRC susceptibility in Tunisians. SUBJECTS AND METHODS: Retrospective case-control study. Study subjects comprised 293 patients with CRC, and 268 age-, gender-, and BMI-matched healthy controls. IL-17A genotyping was done by real-time PCR, with defined clusters. RESULTS: Of the seven tested IL-17A tag-SNPs, minor allele frequency (MAF) of rs10484879 was significantly higher in CRC patients than control subjects. Heterozygous rs10484879 [OR (95% CI) = 2.63 (1.64-4.21)] was associated with higher risk, while carriage of heterozygous rs3748067 genotype was associated with reduced risk of CRC [OR (95% CI) = 0.56 (0.37-0.84)], respectively. Carriage of rs10484879 minor allele correlated with positive family history of CRC and other cancers (P = 0.002), CRC staging (P = 0.044), CRC treatment (P = 0.038), and with chemo body reaction (P = 0.001). Of the 7 IL-17A variants, 4 were in linkage disequilibrium, hence allowing for construction of 4-locus haplotypes. Varied linkage disequilibrium (LD) was noted between the even tested IL-17A variants, and further analysis was limited to only 4-locus (rs3819024-rs2275913- rs10484879-rs7747909). Haploview analysis identified the 4-locus IL-17A haplotypes AGTG (P < 0.011), and GATG (P = 0.036) to be positively associated with CRC, after controlling key covariates. CONCLUSION: IL-17A rs10484879 SNP, and IL-17A haplotypes AGGTG and GAGTG constitute independent factors of CRC susceptibility. We propose that IL-17A may be a target for future CRC immunotherapy.

Target therapy for metastatic breast cancer.

Breast cancer is the first cancer in women worldwide. Since the previous estimates of WHO in 2008, incidence is increasing and it is estimated that 30% of women will develop immediately a metastatic form. However, advances in molecular biology and the discovery of new therapies have extended significantly the survival of patients and improved the quality of life of patients with metastatic breast cancer. The study of gene expression and protein profile has resulted in a finer classification of breast cancer and adapt the treatment of patients according to their molecular profiles. The purpose of our work is to describe the different targeted therapies used in the MBC and their action's mechanism   referring to various therapeutic trials described in the literature.

Analysis of prognostic factors of nephroblastoma in a Tunisian cohort.

BACKGROUND: Nephroblastoma is the most common childhood abdominal malignancy. Many studies allowed a better understanding of prognostic factors and they permitted to adapt treatment according to a risk stratification approach. AIM: To assess the most significant factors influencing the survival of patients presenting nephroblastoma. METHODS: We conducted a retrospective study over a 10-year period between 2001 and 2010 including 42 nephrectomy specimens, assessed in the pathology department of Salah Azaiz Institute, from all children diagnosed with nephroblastoma. The tumors were subdivided into histological subtypes and histological risk groups according to the SIOP-2001 classification. Statistical analyses were performed using the Kaplan-Meir and the Cox regression methods. RESULTS: The median age was 38 months. The mixed type was the most common (40% of cases). The tumors were subdivided into intermediate histological risk group (81%) and high risk group (14%). The tumors were classified as stage I (38%), stage II (24%), stage III (9%), stage IV (17%) and stage V (12%). The four-year survival rate was 83% and the event free survival rate was 85%. Age, laterality, histological risk group, tumor volume, blastema volume, stage, capsular rupture and incomplete resection had a significant impact on survival. Predictive factors of relapse were: laterality, tumor volume, blastema volume, histological risk group, stage, capsular rupture and incomplete resection. CONCLUSION: Histological type and stage were identified as the most important prognostic factors in nephroblastoma. Further large studies are needed to establish the impact of absolute blastemal volume.

TLR2 (-196 to -174 Ins/Del) and TLR3 (1377C>T) as biomarkers for nasopharyngeal cancer in Tunisia

Background/aim: We evaluated the association of TLR2 (-196 to -174 Ins/Del) and TLR3 (1377 C>T) as potential risk factors for nasopharyngeal carcinoma (NPC) in Tunisians. Material and methods: The study subjects comprised 137 NPC patients and 164 cancer-free control subjects. TLR2 genotyping was done by PCR and TLR3 genotyping was performed by PCR-RFLP. Results: Minor allele frequency (MAF) and genotypes of TLR3 (1377 C>T) were comparable between NPC patients and controls. Significantly higher MAF and TLR2-containing Del allele genotypes of TLR2 (-196 to -174 Ins/Del) were seen in NPC patients compared to controls [OR (95% CI) = 2.10 (1.43-3.08), P < 0.001 and OR (95% CI) = 2.07 (1.27-3.37), P = 0.003]. In addition, higher increased NPC risk was associated with the TLR2-Del/Del genotype [OR (95% CI) = 2.74 (1.37-5.48), P = 0.004]. An increased frequency of the Del-T haplotype was seen in NPC cases compared to controls. Conclusion: Our results demonstrate an increased risk of NPC with the TLR2-Del/Del genotype and Del-T TLR2 and TLR3 haplotype, suggesting their potential use as biomarkers to evaluate NPC risk in Tunisians.

Common variants in IL-1RN, IL-1ß and TNF-α and the risk of ovarian cancer: a case control study.

AIM OF THE STUDY: Several studies implicated altered inflammatory response in the susceptibility to ovarian cancer, and polymorphisms in inflammatory cytokines were shown to play an important role in the development of malignancies, including ovarian cancer (OC). Here we investigated the relationship between polymorphisms in IL-1ß (-511C>T), IL-1RN VNTR, TNF-α (-308G>A), and TNF RII (-322 VNTR) and OC risk in Tunisian women. METHODS AND RESULTS: Study subjects comprised 62 OC patients and 126 healthy women. Genotyping was done from genomic DNA obtained from blood simple by PCR. Positive association between IL-1RN (-VNTR) A1 allele (p = 0.0069; OR = 2.04; 95% CI:1.17-3.58) and OC risk, while negative association was seen with the A3 allele (P = 0.0034; OR = 0.09; 95% CI: 0.00-0.64), suggesting a protective role by the A3 allele. For IL-1ß (-511C>T), homozygous C/C genotype was associated with significantly increased risk of OC (p = 0.0002; OR = 4.14; 95% CI: 1.77-9.76), while heterozygote C/T genotype was linked with reduced risk of OC (p = 0.0033; OR = 0.40; 95% CI: 0.20-0.78). Furthermore, TNF-α -308A allele was significantly associated with heightened risk of OC (p = 0.016; OR = 1.70; 95% CI: 1.08-2.69), and homozygote G/G genotype was associated with decreased risk of OC (p = 0.0018; OR = 0.25; 95% CI: 0.09-0.66). In contrast, TNFRII (-322 VNTR) polymorphism was not associated with altered OC risk in the studied group. CONCLUSIONS: The significant association between IL-1RN VNTR, IL1-ß (-511), TNF-α (-308) and OC susceptibility in Tunisian women confirms a role for altered inflammatory response in ovarian cancer pathogenesis.