title: Involvement of IL17A, IL17F and IL23R Polymorphisms in Colorectal Cancer Therapy.
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.
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Inés
authors.initials: I
authors.lastname: Omrane
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Medimegh
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Olfa
authors.initials: O
authors.lastname: Baroudi
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Hager
authors.initials: H
authors.lastname: Ayari
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Walid
authors.initials: W
authors.lastname: Bedhiafi
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Nejla
authors.initials: N
authors.lastname: Stambouli
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Marwa
authors.initials: M
authors.lastname: Ferchichi
authors.affiliation: Laboratory of Anatomy and Cytopathology of the Charles Nicolle Hospital, Tunis, Tunisia.
authors.forename: Nadia
authors.initials: N
authors.lastname: Kourda
authors.affiliation: Laboratory of Diagnostic and Molecular Genetics, Centre Jean Perrin, Clermont Ferrand, France.
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.affiliation: Laboratory of Diagnostic and Molecular Genetics, Centre Jean Perrin, Clermont Ferrand, France.
authors.forename: Nancy
authors.initials: N
authors.lastname: Uhrhammer
authors.affiliation: Medical Oncology Department of the Institute Salah Azaiez, Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Mezlini
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Karim
authors.initials: K
authors.lastname: Bougatef
authors.affiliation: Laboratory of Genetics, Immunology and Human Pathology, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis, Tunisia.
authors.forename: Amel
authors.initials: A
authors.lastname: Benammar-Elgaaied
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery / Q000628:therapy*; D005260:Female; D005720:Gamma Rays / Q000627:therapeutic use*; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011110:Polymorphism, Genetic; D018123:Receptors, Interleukin / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; C508717:IL17A protein, human; C440021:IL17F protein, human; C515500:IL23R protein, human; D020381:Interleukin-17; D018123:Receptors, Interleukin