Abstract
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.
Highlights
Cytokines are parts of the extracellular signaling network that controls every function of the innate and specific immune responses by operating in anautocrine or paracrine manner
We suggest that IL17A G197A, IL17F rs763780and IL23R rs10889677 polymorphisms are associated with the development and progression of colorectal cancer[21, 22]
To confirm that IL17F rs763780and IL23R rs10889677 polymorphisms were associated with the tumor location, we evaluate the relationship between colon cancer susceptibility and these two polymorphisms
Summary
Cytokines are parts of the extracellular signaling network that controls every function of the innate and specific immune responses by operating in anautocrine or paracrine manner. They are similar to hormones but they may be distinguished in particular by a more pleiotropic action and production involving a greater number of cell types. Taking into account their important role in immune responses, their therapeutic value in several contexts of immunological and infectious diseases seems obvious. The IL17 induces the recruitment of immune cells in peripheral tissues This response requires the activation of NF-kB after the commitment of IL17 to its receptor IL17R. There are two forms of IL 17: the IL17A and IL17F that act through a complex of two chains of IL17RA and IL17RC receptor
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