HLA class II polymorphism: Protective or risk factors to breast cancer in Tunisia?

HLA system plays a key role in the tumor cells’ escape from immune surveillance. Herein is the first report on the correlation of the susceptibility to breast cancer with HLA class II markers in Tunisia. Molecular typing of HLA-DRB1 and -DQB1 loci was undertaken for 70 Tunisian female patients. Comparison of allele and haplotype distribution between patients and 70 female control subjects reveals a negative association between HLA-DRB1*07-DQB1*02 and the incidence of breast cancer in the Tunisian population. (Pathology Oncology Research Vol 12, No 2, 79–81)     

Concurrent renal artery stent during endovascular infrarenal aortic aneurysm repair confers higher risk for 30-day acute renal failure

Objective

Concurrent renal artery angioplasty and stenting (RAAS) during endovascular aneurysm repair (EVAR) of infrarenal abdominal aortic aneurysm (AAA) has been practiced in an attempt to maintain renal perfusion. The aim of this study was to identify the current practice of RAAS during EVAR and its effect on perioperative renal outcome.

Evaluation of Toll-Like Receptors 2/3/4/9 Gene Polymorphisms in Cervical Cancer Evolution

Accumulative epidemiological evidence suggests that polymorphisms of Toll-like receptors signaling pathway elucidated the cellular and molecular mechanisms of human diseases whose gaining a primordial importance. The aim of our study is to identify the role of TLR 2 (?196 to ?174 del), TLR 3 (1377 C>T), TLR 4 (Asp299Gly) and TLR 9 (G2848A) gene polymorphisms with the evolution of cervical cancer in Tunisian women. Blood samples were collected from histopathologically confirmed patients with cervical cancer and unrelated healthy female controls of similar ethnicity. Genotyping of the analyzed polymorphisms were done using Polymerase Chain Reaction and Restriction Fragment Length Polymorphism. For the TLR 2, Ins/Ins genotype is a protector factor [p = 0.006; OR: 0.35(0.16–0.73)] and the dominant genotype of TLR 3 increased the risk of CC in stage (III+IV); C/C versuss C/T [p = 0.033; OR: 2.03(1.00–4.13)] and C/C versus C/T+T/T [p = 0.036; OR: 1.93(1.00–3.74)]. For TLR 4, the dominant genotype Asp/Asp is implicated in the occurrence of CC in stage (I+II) [p = 0.000; OR: 4.55(1.58–13.06)], [p = 0.001; OR: 3.49(1.44–8.45)] and in stage (III+IV) [p = 0.038; OR: 3.77(0.87–16.29)], [p = 0.007; OR: 5.21(1.65–16.46)] and the major allele Asp is a risk factor for the development of tumor in stage (I+II). The TLR2 Ins/Del genotype is associated with tumor evolution to stage (III+IV) [p = 0.003; OR: 3.00 (1.22–7.35)] and the genotypes Gly/Gly and Asp/Gly+Gly/Gly and Gly allele of TLR 4 are implicated in tumor evolution to the advanced stages. Further, TLR 2, TLR 3, TLR 4 and TLR 9 gene polymorphisms are implicated in the modulation of CC risk due to tobacco usage and statue of menopause among cases. Our study suggests a relationship between the incidence of the TLR2, TLR 3, TLR 4 and TLR9 mutations and the clinical progression of CC according to the FIGO classification. However, future studies with different demographic and clinical characteristics in ethnically diverse populations may provide a more comprehensive involvement of innate immunity in cervical cancer etiology in women worldwide.     

Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

HCV has been associated with a pro‐inflammatory state, which predisposes to hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on HCC progression remain unclear. Although HCV infection illustrates the potential role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment‐induced HCV eradication. We studied the possible role of HCV infection in the processes of HCC initiation and performed a systematic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein‐proteins interactions (PPI) networks. On the basis of our analysis performed, we identified key hub proteins related to HCV‐treatment response infection and to HCC development. Host genetic polymorphisms, such as inosine triphosphatase (ITPA), interferon, lambda 3 (IFNL3), Q5 interferon, lambda 4 (IFNL4), toll‐like receptors (TLRs) and interferon‐stimulated gene 15 (ISG‐15), were identified as key genes for treatment prediction and HCC evolution. By comparing unique genes for HCV‐treatment response and genes particular to HCV‐HCC development, we found a common PPI network that may participate in more extensive signalling processes during anti‐HCV treatment, which can play important roles in modulating the immune response to the occurrence of HCC. Data mining is an effective tool for identifying potential regulatory pathways involved in treatment response and HCC development. Our study may contribute to a better understanding of HCV immunopathogenesis and highlights the complex role of host genetics in HCV clearance.     

Timing of breast cancer surgery in relation to menstrual cycle phase: no effect on 3-year prognosis: the ITS Study

The effect of breast cancer surgery timing during the menstrual cycle on prognosis remains controversial. We conducted a multicentre prospective study to establish whether timing of interventions influences prognosis. We report 3-year overall and disease-free survival (OS/DFS) results for 'primary analysis' patients (regular cycles, no oral contraceptives within previous 6 months). Data were collected regarding timing of interventions in relation to patients' last menstrual period (LMP) and first menstrual period after surgery (FMP). Hormone profiles were also measured. Cox's proportional hazards model incorporated LMP in continuous form. Exploratory analyses used menstrual cycle categorisations of Senie, Badwe and Hrushesky. Hormone profiles with LMP and FMP data were also used to define menstrual cycle phase. Four hundred and twelve 'primary analysis' patients were recruited. Three-year OS from first surgery was 90.7, 95% confidence interval (CI) [87.9, 93.6%]. Menstrual cycle according to LMP was not statistically significant (OS: hazard ratio (HR)=1.02, 95%CI [0.995,1.042], P=0.14; DFS: HR=1.00, 95%CI [0.980,1.022], P=0.92). Timing of surgery in relation to menstrual cycle phase had no significant impact on 3-year survival. This may be due to 97% of patients receiving some form of adjuvant therapy. Survival curves to 10 years indicate results may remain true for longer-term survival.     

Effect of Follicle Stimulating Hormone Receptor Gene Polymorphisms in Cervical Cancer Risk

For the first time in the word, we investigated the association between five FSHR polymorphisms with the risk of cervical cancer among Tunisians. Study subjects comprised 112 Cervical Cancer (CC) patients and 164 control women. Genotyping of FSHR rs6166, rs1007541, rs11692782, rs2055571 and rs1394205 variants was done by realtime PCR, with defined clusters. The allelic distributions of the tested FSHR SNPs were comparable between CC patients and control women. In contrast, the heterozygous genotype of rs1007541 was associated with 1.8-fold increased risk of CC. Stratification according to FIGO staging revealed that the minor allele of rs1007541 was more frequent among advanced tumor stage patients, with 11-fold increased risk of CC [P < 0.0001; OR (95 % CI) = 11.32 (7.46–17.18)]. However, no significant allelic association was revealed in the rest of analyzed FSHR SNPs. Haploview analysis showed high Linkage disequilibrium (LD) between rs2055571 and rs1394205. Haplotype analysis revealed a lack of association between cases and controls. However, analysis of CC patient subgroups demonstrated enrichment of GGTAG haplotype in early tumor stage [P = 0.025; OR (95 % CI) = 0.07 (0.01–0.70)]. The FSHR variants and haplotypes may be a genetic markers for CC susceptibility and evolution among Tunisian women.     

Composition corporelle des patients atteints de BPCO et son impact sur la fonction respiratoire

Introduction:

Despite fat-free mass index (FFMI) is one of the strongest predictive factors of survival during chronic obstructive pulmonary disease (COPD), there is a considerable lack of information regarding body composition in Tunisian patients with COPD.   Aim: Describe the body composition of Tunisian patients followed for COPD and examine the relationship between body composition and the severity of the disease.

Methods:

Cross-sectional study of patients with stable COPD. Body composition was assessed by bioelectrical impedance analysis. Pulmonary function tests (PFT) included spirometry with plethysmography and the six-minute walking test. The severity of dyspnea was assessed by the mMRC scale.

Results:

During the study period, 104 patients with stable COPD were included (average age= 65.9 years and average FEV1= 49.3%). Fifty-four percent of patients were GOLD D stage. According to the IMM, malnutrition was identified in 20.2% of cases. Patients with low FFMI were the most symptomatic, had a more severe air flow limitation and a more severe disease. The walking distance was lower in malnourished patients. However, FFMI was not significantly associated with exercise capacity.

Conclusions:

Malnutrition is highly prevalent in COPD patients and is correlated to the severity of the disease. Thus, body composition analysis should be considered in COPD patient management.     

Predictors of acute kidney injury after infrarenal abdominal aortic aneurysm repair in octogenarians

Objective

Acute kidney injury (AKI) is a common postoperative complication after abdominal aortic aneurysm (AAA) repair and is associated with significant morbidity and mortality. However, limited studies have investigated this complication in elderly patients. This study aims to evaluate AKI in octogenarians after open endovascular AAA repair (OAR) and endovascular AAA repair (EVAR).