Association of interleukin-17A polymorphisms with the risk of colorectal cancer: A case-control study. (October 2018)

• Record Type: Journal Article
• Authors: Bedoui, Sinda A.; Barbirou, Mouadh; Stayoussef, Mouna; Dallel, Meriem; Mokrani, Amina; Makni, Lamia; Mezlini, Amel; Bouhaouala, Balkiss; Yacoubi-Loueslati, Besma; Almawi, Wassim Y.
• Is Part Of: Cytokine. Volume 110(2018)
• Page Start: 18
• Page End: 23
• Publication Date: 2018-10
• Subjects: Colorectal cancer -- Genotype -- Haplotype -- Interleukin-17 -- Polymorphism; BMI body-mass index -- CRC colorectal cancer -- IL-17 interleukin-17 -- LD linkage disequilibrium -- MAF minor allele frequency -- SNP single nucleotide polymorphisms; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2018.04.017
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Minor allele frequency of rs10484879 was higher in CRC patients than control subjects. Carriage of heterozygous rs3748067 genotype was associated with reduced risk of CRC. rs10484879 minor allele correlated with CRC family history, staging and treatment. Haploview identified AGT G and GAT G haplotypes to be positively associated with CRC. 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 AGT G ( P < 0.011), and GAT G ( P = 0.036) to be positively associated with CRC, after controlling key covariates. Conclusion: IL-17A rs10484879 SNP, and IL-17A haplotypes AGGT G and GA GT G constitute independent factors of CRC susceptibility. We propose that IL-17A may be a target for future CRC immunotherapy.