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. 2015 Jun 17;10(6):e0128911.
doi: 10.1371/journal.pone.0128911. eCollection 2015.

Involvement of IL17A, IL17F and IL23R Polymorphisms in Colorectal Cancer Therapy

Inés Omrane  1 , Imen Medimegh  1 , Olfa Baroudi  1 , Hager Ayari  1 , Walid Bedhiafi  1 , Nejla Stambouli  1 , Marwa Ferchichi  1 , Nadia Kourda  2 , Yves-Jean Bignon  3 , Nancy Uhrhammer  3 , Amel Mezlini  4 , Karim Bougatef  1 , Amel Benammar-Elgaaied  1
Affiliations

Involvement of IL17A, IL17F and IL23R Polymorphisms in Colorectal Cancer Therapy

Inés Omrane et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. IL17F genotypes impact on overall survival stratified by surgery.
(A) palliative surgery and (B) radical surgery; in CRC patients according to IL17F genotype (IL17F AA vs. IL17F AGGG). P-values from the log-rank test are indicated. OS: overall survival.
Fig 2
Fig 2. IL17F genotypes impact on overall survival stratified by neoadjuvant chemotherapy.
(A) withoutneoadjuvant chemotherapy (p = 0,003) and (B) with neoadjuvant chemotherapy (p = 0,026); in CRC patients according to IL17F genotype (IL17F AA vs. IL17F AGGG). P-values from the log-rank test are indicated. OS: overall survival.
Fig 3
Fig 3. IL17F genotypes impact on overall survival stratified by radiotherapy.
(A) without radiotherapy and (B) with radiotherapy; in CRC patients according to IL17F genotype (IL17F AA vs. IL17F AGGG). P-values from the log-rank test are indicated. OS: overall survival.
Fig 4
Fig 4. IL17F genotypes impact on overall survival stratified by chemotherapy.
(A) Without chemotherapy and (B) with chemotherapy; in CRC patients according to IL17F genotype (IL17F AA vs. IL17F AGGG). P-values from the log-rank test are indicated. OS: overall survival.
See this image and copyright information in PMC

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