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

Sinda A Bedoui (1) , Mouadh Barbirou (2, 1) , Mouna Stayoussef (1) , Meriem Dallel (3) , Amina Mokrani (4) , Lamia Makni (3) , Amel Mezlini (4) , Balkiss Bouhaouala (2, 5) , Besma Yacoubi-Loueslati (1) , Wassim Almawi (6, 1)

1 FST - Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis
2 LR11IPT08 - Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules
3 FPHM - Faculté de Pharmacie [Monastir]
4 ISA - Institut Salah Azaiz [Tunis]
5 UTM - Université de Tunis El Manar
6 LAU - Lebanese American University

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 dis-equilibrium, 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.

Mots clés: Colorectal cancer; Genotype; Interleukin-17; Haplotype; Polymorphism

Domaines: Cancer

Sinda A Bedoui, Mouadh Barbirou, Mouna Stayoussef, Meriem Dallel, Amina Mokrani, et al.. Association of interleukin-17A polymorphisms with the risk of colorectal cancer: A case-control study. Cytokine, 2018, 110, pp.18-23. ⟨10.1016/j.cyto.2018.04.017⟩. ⟨pasteur-02009143⟩