Association of interleukin-17A polymorphisms with the risk of colorectal cancer: A case-control study

Sinda A Bedoui; Mouadh Barbirou; Mouna Stayoussef; Meriem Dallel; Amina Mokrani; Lamia Makni; Amel Mezlini; Balkiss Bouhaouala; Besma Yacoubi-Loueslati; Wassim Y Almawi

doi:10.1016/j.cyto.2018.04.017

Association of interleukin-17A polymorphisms with the risk of colorectal cancer: A case-control study

Cytokine. 2018 Oct:110:18-23. doi: 10.1016/j.cyto.2018.04.017. Epub 2018 Apr 22.

Authors

Affiliations

¹ Department of Biology, Faculty of Sciences of Tunis, Laboratory of Mycology Pathologies and Biomarkers, El Manar University, Tunis LR16ES05, Tunisia.
² Department of Biology, Faculty of Sciences of Tunis, Laboratory of Mycology Pathologies and Biomarkers, El Manar University, Tunis LR16ES05, Tunisia; Laboratory of Venoms and Therapeutic Molecules, Pasteur Institute of Tunis, Tunisia.
³ Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), University of Monastir, Monastir, Tunisia.
⁴ Salah Azeiz Oncology Institute, Tunis, Tunisia.
⁵ Laboratory of Venoms and Therapeutic Molecules, Pasteur Institute of Tunis, Tunisia; Medical School of Tunis, University of Tunis El Manar, Tunisia.
⁶ Department of Biology, Faculty of Sciences of Tunis, Laboratory of Mycology Pathologies and Biomarkers, El Manar University, Tunis LR16ES05, Tunisia; School of Pharmacy, Lebanese American University, Byblos, Lebanon. Electronic address: wassim.almawi@lau.edu.lb.

PMID: 29689450
DOI: 10.1016/j.cyto.2018.04.017

Abstract

Background: Interleukin (IL)-17A is proinflammatory cytokine produced by Th17 cells, which play key, but sometimes inconsistent role in autoimmunity and cancer. Polymorphic variants in IL-17A gene were differentially associated with susceptibility to cancer, including colorectal cancer (CRC).

Aim: We investigated the association between six IL-17A gene variants (rs3819024, rs2275913, rs3819025, rs10484879, rs7747909, and rs3748067) with CRC susceptibility in Tunisians.

Subjects and methods: Retrospective case-control study. Study subjects comprised 293 patients with CRC, and 268 age-, gender-, and BMI-matched healthy controls. IL-17A genotyping was done by real-time PCR, with defined clusters.

Results: Of the seven tested IL-17A tag-SNPs, minor allele frequency (MAF) of rs10484879 was significantly higher in CRC patients than control subjects. Heterozygous rs10484879 [OR (95% CI) = 2.63 (1.64-4.21)] was associated with higher risk, while carriage of heterozygous rs3748067 genotype was associated with reduced risk of CRC [OR (95% CI) = 0.56 (0.37-0.84)], respectively. Carriage of rs10484879 minor allele correlated with positive family history of CRC and other cancers (P = 0.002), CRC staging (P = 0.044), CRC treatment (P = 0.038), and with chemo body reaction (P = 0.001). Of the 7 IL-17A variants, 4 were in linkage disequilibrium, hence allowing for construction of 4-locus haplotypes. Varied linkage disequilibrium (LD) was noted between the even tested IL-17A variants, and further analysis was limited to only 4-locus (rs3819024-rs2275913- rs10484879-rs7747909). Haploview analysis identified the 4-locus IL-17A haplotypes AGTG (P < 0.011), and GATG (P = 0.036) to be positively associated with CRC, after controlling key covariates.

Conclusion: IL-17A rs10484879 SNP, and IL-17A haplotypes AGGTG and GAGTG constitute independent factors of CRC susceptibility. We propose that IL-17A may be a target for future CRC immunotherapy.

Keywords: Colorectal cancer; Genotype; Haplotype; Interleukin-17; Polymorphism.

MeSH terms

Alleles
Case-Control Studies
Colorectal Neoplasms / genetics*
Female
Gene Frequency / genetics
Genetic Predisposition to Disease / genetics*
Haplotypes / genetics
Humans
Interleukin-17 / genetics*
Linkage Disequilibrium / genetics
Male
Middle Aged
Polymorphism, Single Nucleotide / genetics*
Retrospective Studies

Substances

IL17A protein, human
Interleukin-17