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Interleukin-17A polymorphisms predict the response and development of tolerance to FOLFOX chemotherapy in colorectal cancer treatment

Cancer Gene Therapy volume 27, pages 311–318 (2020)Cite this article

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Abstract

Polymorphic variants in IL-17A gene were differentially associated with colorectal cancer (CRC) susceptibility but their link with response and toxicity to CRC treatment have not yet been evaluated. We investigated association between seven IL-17A variants with the response and toxicity to CRC treatment in 294 patients with CRC. IL-17A genotyping was done by real-time PCR. MAF of rs3748067 was significantly higher in CRC cases resistant to FOLFOX treatment (R+) than non resistant (R−). Significantly higher rs3804513 MAF was noted in R+ versus R− colon cancer (CC). Higher rs2275913 and rs10484879, and reduced rs3804513 MAF were seen in rectal cancer (RC) tolerant to FOLFOX (T+) compared to (T−) patients. Strong association of rs3819025, rs3804513, and rs7747909 was found with tolerance to RC treatment. rs3748067 was associated with FOLFOX tolerance in CC but not RC. Significant higher frequency of AGGCAGG and GAGCAGG haplotypes was seen among R + CC, thus assigning non-favorable nature to these haplotypes. Higher and lower frequencies of GAGTAAG and AGGCTGA haplotypes, respectively, were observed in T + RC, thereby assigning FOLFOX-tolerant and non-tolerant nature to these haplotypes. The obtained results suggest that IL-17A variants and haplotypes may be a target for future management of CRC treatment.

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Acknowledgements

We thank all blood donors and the patients with CRC who participated in the present study. This study was funded in part by the Ministry of High Education and Scientific Research and the National Agency of Promotion of Research, Project 2017 D4P1.

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Authors and Affiliations

  1. Department of Biology, Faculty of Sciences of Tunis, Laboratory of Mycology Pathologies and Biomarkers, El Manar University, LR16ES05, Tunis, Tunisia

    Sinda Bedoui, Mouna Stayoussef, Wassim Y. Almawi & Besma Yacoubi-Loueslati

  2. Lab. Human Genome and Multifactorial Diseases, University of Monastir, Monastir, Tunisia

    Meriem Dallel

  3. Laboratory of Venoms and Therapeutic Molecules, Pasteur Institute of Tunis, University of Tunis El Manar, 13 Place Pasteur, BP74, 1002, Tunis, Tunisia

    Mouadh Barbirou & Balkiss Bouhaouala

  4. Salah Azaiez Oncology Institute, Tunis, Tunisia

    Amina Mokrani & Amel Mezlini

  5. Medical School of Tunis, University of Tunis El Manar, Tunis, Tunisia

    Balkiss Bouhaouala

  6. Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, Kazakhstan

    Wassim Y. Almawi

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  1. Sinda Bedoui
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Bedoui, S., Dallel, M., Barbirou, M. et al. Interleukin-17A polymorphisms predict the response and development of tolerance to FOLFOX chemotherapy in colorectal cancer treatment. Cancer Gene Ther 27, 311–318 (2020). https://doi.org/10.1038/s41417-019-0102-1

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