RESUMO
Interleukin (IL) 17A is an inflammatory cytokine expressed by Th 17 cells and plays a role in tissue inflammation by inducing release of proinflammatory and neutrophil-mobilizing cytokines. We have investigated the association between colorectal cancer and polymorphisms of IL17A (rs2275913. G197A). The study was performed in 241 subjects (102 with colorectal cancer and 139 healthy controls). Genotypes were determined by fluorescent-based restriction fragment length polymorphism method. The association between the molecular features at the gene in relation to tumor and patient clinical characteristics was analyzed. There was a significant difference between the genotype frequencies of IL17A G197A of control subjects (GG 68.34 % and GA + AA 31.65 %) and patients with colorectal cancer (GG 47.05 % and GA + AA 52.94 %) (p = 0.001 with odds ratio (OR) 2.45 (1.43-4.11)). IL17A G197A polymorphism is particularly associated with colon cancer. Indeed, the IL17A GG genotype could be considered as a protective factor against colon cancer (p = 0.00001) with OR 3.77 (2.04-6.99). We have noted a significant association of IL17A G197A polymorphism not only with tumor localization (p = 0.003) but also with tumor differentiation (p = 0.0005) in CRC patients. We have also showed a significant association of G197A variant with an increased risk of advanced stage (p = 0.005). Our result suggests that the A allele of IL17A gene is involved in susceptibility to colorectal cancer and is associated with clinical features as tumor location, tumor differentiation, and TNM stage. IL17A polymorphism may serve as biomarker of disease location and progression.
Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Interleucina-17/genética , Adulto , Idoso , Povo Asiático/genética , Neoplasias Colorretais/patologia , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The recently identified class of microRNAs (miRs) provided a new insight into cancer research, since abnormalities of members of microRNAs family have been found in various types of cancer. However, the relationship between five miRNAs (miR146a, miR155, miR21, miR135a, and miR147b) and colorectal cancer remains unclear. In the present study, we examined expression of these miRNAs in 25 pair-matched colon cancer tissues and normal colon mucosa. The expression levels of miR146a, miR155, miR21, miR135a, and miR147b were quantified by real-time PCR. We found that miR21, miR146a, and miR135a were all expressed at higher levels in colon tumors. On the other hand, miR146a and miR147b expressions are significantly higher in left colon compared to right colon. These two miRs, especially miR146a, seemed to be markers for the left colon tumors. Moreover, significant proportional and inverse correlations were found between miR expressions in tumor and healthy tissue, and the correlations profiles were different depending on cancer localization. Taken together, these results lead us to suggest the presence of different mechanisms regulating miRs expression and consequently their target genes in left and right colon. So the pathway of colorectal carcinogenesis would be different according to the site of the tumor.
Assuntos
Biomarcadores Tumorais/análise , Colo/química , Neoplasias Colorretais/metabolismo , MicroRNAs/análise , Biomarcadores Tumorais/química , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Colo/metabolismo , Neoplasias Colorretais/química , Feminino , Humanos , Masculino , MicroRNAs/química , MicroRNAs/genética , MicroRNAs/metabolismo , Curva ROCRESUMO
In our study, we investigate the possible association of thymidylate synthase polymorphism, 28 bp tandem repeat in 5'-UTR (transcription enhancer element) with susceptibility of colorectal and gastric cancer in Tunisian population. Because thymidylate synthase provides an effective prediction of chemotherapy treatment based on 5-fluorouracil, our interest in this study was focused on finding an eventual interaction between thymidylate synthase polymorphism and treatment of sporadic colorectal and gastric cancer. Whole blood was collected into EDTA tube, after centrifugation for 15 min, the buffy coat was isolated, and genotyping of TS 5'-UTR polymorphism was carried by polymerase chain reaction method using appropriate primers. Determination of the different genotypes was done directly on the stained agarose gel. Our finding showed that the 5'tandem repeat polymorphism of the thymidylate synthase gene is associated with risk of colorectal cancer; thus, LL (3R/3R) genotype is significantly high in patients with colorectal cancer compared to controls (P = 0.002; OR 2.7; 95 % CI 1.4-5.2). In addition, we found a positive association between SL (2R/3R) genotype in the thymidylate synthase 5'-UTR and gastric cancer risk (P = 0.015; OR 4.46; 95 % CI 1.08-19.64). Furthermore, we found a correlation of thymidylate synthase polymorphism with the fluorouracil-based therapy regimes and also with preoperatory radiation in patients with colorectal cancer. Thymidylate synthase is associated with risk of colorectal cancer but not with gastric cancer; however, heterozygous SL (2R/3R) polymorphism is associated with risk of gastric cancer; moreover, the 5' tandem repeat polymorphism of thymidylate synthase gene was an independent predictor of the clinical treatment.
Assuntos
Regiões 3' não Traduzidas/genética , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/etiologia , Fluoruracila/uso terapêutico , Polimorfismo Genético/genética , Neoplasias Gástricas/etiologia , Timidilato Sintase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Regiões Promotoras Genéticas/genética , Fatores de Risco , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Sequências de Repetição em Tandem/genética , Tunísia/epidemiologiaRESUMO
Chronic inflammation is closely linked to cancer. The risk of damage by colorectal cancer (CRC) may increase due to autoimmune disease and cryptogenic inflammation. Therefore, genetic factors implicated in the chronic irritation in inflammatory bowel disease such as NOD2/CARD15 may predispose to CRC. In this report, we shed the light on the possible contribution of the NOD2 3020insC variant to CRC risk in a series of 246 Tunisian subjects including 101 patients with CRC and 145 healthy controls. NOD2/CARD15 polymorphism was genotyped by sizing fluorescently labeled PCR products and automated sequencers. We analyzed the association between the molecular features at this gene in relation to tumor and patient characteristics and treatments. Through this qualitative analysis, we found that CRC patients with mutant allele of NOD2/CARD15 were suffering from Crohn's disease (CD) with canonic presentation. We also observed a positive association between 3020insC polymorphism and surgery and chemotherapy. We suppose that around 3% of colorectal cases which happen at an age older than 50 years are associated with the canonic form of CD along with the 3020insC mutation and that these patients are in need for chemotherapy.