Association of interleukin-17A polymorphisms with the risk of colorectal cancer: A case-control study.
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.
['Bedoui|Sinda A|SA|', 'Barbirou|Mouadh|M|', 'Stayoussef|Mouna|M|', 'Dallel|Meriem|M|', 'Mokrani|Amina|A|', 'Makni|Lamia|L|', 'Mezlini|Amel|A|', 'Bouhaouala|Balkiss|B|', 'Yacoubi-Loueslati|Besma|B|', 'Almawi|Wassim Y|WY|']
D000483:Alleles D016022:Case-Control Studies D015179:Colorectal Neoplasms D005260:Female D005787:Gene Frequency D020022:Genetic Predisposition to Disease D006239:Haplotypes D006801:Humans D020381:Interleukin-17 D015810:Linkage Disequilibrium D008297:Male D008875:Middle Aged D020641:Polymorphism, Single Nucleotide D012189:Retrospective Studies
Polymorphism Colorectal cancer Genotype Haplotype Interleukin-17