Omrane Inés, Marrakchi Raja, Baroudi Olfa, Mezlini Amel, Ayari Hager, Medimegh Imen, Stambouli Nejla, Kourda Nadia, Bouzaienne Hassen, Uhrhammer Nancy, Bougatef Karim, Bignon Yves-Jean Jean, Benammar-Elgaaied Amel
Laboratory of Human Genetics Immunology and Pathology, Faculty of Sciences Tunis, University of Tunis El Manar, El Manar, Tunis, 209, Tunisia,
Tumour Biol. 2014 Jul;35(7):6627-32. doi: 10.1007/s13277-014-1890-4. Epub 2014 Apr 4.
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.
白细胞介素(IL)-17A是一种由Th17细胞表达的炎性细胞因子,通过诱导促炎细胞因子和中性粒细胞动员细胞因子的释放,在组织炎症中发挥作用。我们研究了白细胞介素-17A(IL17A,rs2275913,G197A)基因多态性与结直肠癌之间的关联。该研究纳入了241名受试者(102例结直肠癌患者和139名健康对照)。采用基于荧光的限制性片段长度多态性方法确定基因型。分析了该基因的分子特征与肿瘤及患者临床特征之间的关联。对照受试者(GG占68.34%,GA+AA占31.65%)与结直肠癌患者(GG占47.05%,GA+AA占52.94%)的IL17A G197A基因型频率存在显著差异(p = 0.001,优势比(OR)为2.45(1.43 - 4.11))。IL17A G197A多态性尤其与结肠癌相关。实际上,IL17A GG基因型可被视为预防结肠癌的保护因素(p = 0.00001),OR为3.77(2.04 - 6.99)。我们注意到,在结直肠癌患者中,IL17A G197A多态性不仅与肿瘤定位(p = 0.003)显著相关,还与肿瘤分化(p = 0.0005)显著相关。我们还发现G197A变异与晚期风险增加显著相关(p = 0.005)。我们的结果表明,IL17A基因的A等位基因与结直肠癌易感性有关,并与肿瘤位置、肿瘤分化和TNM分期等临床特征相关。IL17A多态性可能作为疾病定位和进展的生物标志物。