Omrane Inés, Medimegh Imen, Baroudi Olfa, Ayari Hager, Bedhiafi Walid, Stambouli Nejla, Ferchichi Marwa, Kourda Nadia, Bignon Yves-Jean, Uhrhammer Nancy, Mezlini Amel, Bougatef Karim, Benammar-Elgaaied Amel
Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
Laboratory of Anatomy and Cytopathology of the Charles Nicolle Hospital, Tunis, Tunisia.
PLoS One. 2015 Jun 17;10(6):e0128911. doi: 10.1371/journal.pone.0128911. eCollection 2015.
IL23/IL17 pathway plays an important role in the development of inflammatory bowel diseases (IBD). In general, the genes encoding the cytokines are genetically polymorphic and polymorphisms in genes IL23R and IL17 have been proved to be associated with its susceptibility to inflammatory diseases as well as cancer including colorectal cancer. Moreover, it has been shown that these interleukins are involved in anti-tumor or pro-tumor effects of various cancers. Previously, we showed that there is a significant association between IL17A, IL17F and IL23R polymorphisms as well as the occurrence of colorectal cancer and the clinical features of the disease. The purpose of the present work is to investigate an association between IL17A, IL17F and IL23R polymorphisms in 102 Tunisian patients with colorectal cancer treatment. The association was analyzed by statistical tools. We found that patients with mutated genotypes of IL17A G197A SNP could be a risk factor for the inefficiency of chemotherapy and radiotherapy. Unlike IL17F variant, patients with wild type genotypes require surgery and adjuvant chemotherapy. On the one hand, we found no evidence that supports a significant association between IL23R polymorphism and the combined genotypes of these three genes and the colorectal cancer treatment. On the other hand, we showed that there is an important interaction between IL17A/IL17F polymorphisms and the stage of the disease as well as its treatment. Finally, patients with IL17F wild type genotype highlighted that there is a valid longer OS without all treatments and with radiotherapy and a neoadjuvant chemotherapy. In contrast, we observed that there are no relationships between IL17A, IL23R and the survival of these patients neither with nor without the treatment. Our results suggest that polymorphisms in IL17A and IL17F genes may be a predictive source of colorectal cancer therapy type. Therefore, IL17F may serve as an independent prognostic factor for overall survival in patients with colorectal cancer.
IL23/IL17信号通路在炎症性肠病（IBD）的发生发展中起重要作用。一般来说，编码细胞因子的基因具有遗传多态性，IL23R和IL17基因的多态性已被证明与炎症性疾病以及包括结直肠癌在内的癌症易感性相关。此外，已表明这些白细胞介素参与各种癌症的抗肿瘤或促肿瘤作用。此前，我们发现IL17A、IL17F和IL23R多态性与结直肠癌的发生及其疾病临床特征之间存在显著关联。本研究的目的是调查102例接受结直肠癌治疗的突尼斯患者中IL17A、IL17F和IL23R多态性之间的关联。通过统计工具分析这种关联。我们发现，IL17A G197A单核苷酸多态性（SNP）突变基因型的患者可能是化疗和放疗无效的危险因素。与IL17F变体不同，野生型基因型的患者需要手术和辅助化疗。一方面，我们没有发现证据支持IL23R多态性与这三个基因的联合基因型和结直肠癌治疗之间存在显著关联。另一方面，我们表明IL17A/IL17F多态性与疾病分期及其治疗之间存在重要相互作用。最后，IL17F野生型基因型的患者表明，在未进行所有治疗以及进行放疗和新辅助化疗的情况下，有有效的更长总生存期（OS）。相比之下，我们观察到IL17A、IL23R与这些患者无论是否接受治疗的生存率之间均无关联。我们的结果表明，IL17A和IL17F基因的多态性可能是结直肠癌治疗类型的预测来源。因此，IL17F可能作为结直肠癌患者总生存期的独立预后因素。
