Nemati Kazem, Golmoghaddam Hossein, Hosseini Seyed Vahid, Ghaderi Abbas, Doroudchi Mehrnoosh
Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, 71348-45794 Shiraz, Iran.
Institute for Colorectal Research Center, Faghihi Hospital, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Gene. 2015 Apr 25;561(1):88-94. doi: 10.1016/j.gene.2015.02.014. Epub 2015 Feb 11.
IL-17 family of cytokines and human IL-23R play important and sometimes contradictory roles in autoimmune and inflammatory diseases as well as human malignancies. Different alleles of this cytokine family may differentially affect IL-17 secretion. We sought to investigate the association of IL-17A, IL-17F and IL-23R gene polymorphisms with the susceptibility to colorectal cancer (CRC).
The IL-17A rs2275913 (G197A), IL-17F rs763780 (T7488C), IL-23R rs11209026 and IL-23R rs1088967 SNPs were detected in 202 patients with colorectal cancer and 203 healthy age/sex matched controls by PCR-RFLP method. For evaluation of the functional relevance of these SNPs with IL-17A and IL-17F production, the serum levels of IL-17A and IL-17F were investigated in 107 and 109 patients as well as 33 and 52 healthy individuals, respectively, by ELISA assays.
The IL-17F TT genotype [OR=0.44, 95% CI: 0.21-0.94, P=0.03] and T allele [OR=0.46, 95% CI: 0.21-1.1, P=0.03] were associated with a decreased risk of CRC compared with the TC genotype and C allele. Moreover, IL-17F TT genotype was significantly associated with well differentiation in tumors (P=0.02). We also observed a significant association between the AG genotype of IL-17A G197A SNP with increased risk of colorectal cancer as compared to AA genotype (P=0.001). The IL-17A concentrations in the sera of patients with CRC were significantly elevated compared to healthy individuals (P=0.008), and serum level of IL-17A was significantly related to tumor size (P=0.043). The A allele of IL-23R rs10889677 polymorphism was marginally associated with increased IL-17A levels in the sera of patients (P=0.08). The genotype distributions of IL-23R rs11209026 and IL-23R rs10889677 SNPs were not significantly different between CRC patients and controls. The haplotypes of IL-17A G197A/IL-17F T7488C and IL-23R were not significantly associated with CRC. No IL-17F was detected in the sera of patients and only one healthy individual had IL-17F in his serum.
Our findings suggest that the T allele of IL-17F T7488C polymorphism may be involved in reduced risk of CRC and IL-17A may be an attractive target for colorectal cancer immunotherapy.
细胞因子白细胞介素-17（IL-17）家族及人类白细胞介素-23受体（IL-23R）在自身免疫性疾病、炎症性疾病以及人类恶性肿瘤中发挥着重要作用，有时作用相互矛盾。该细胞因子家族的不同等位基因可能对IL-17的分泌产生不同影响。我们旨在研究IL-17A、IL-17F和IL-23R基因多态性与结直肠癌（CRC）易感性之间的关联。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，对202例结直肠癌患者及203例年龄/性别匹配的健康对照者检测IL-17A rs2275913（G197A）、IL-17F rs763780（T7488C）、IL-23R rs11209026和IL-23R rs1088967单核苷酸多态性（SNP）。为评估这些SNP与IL-17A和IL-17F产生的功能相关性，分别通过酶联免疫吸附测定（ELISA）法，检测了107例和109例患者以及33例和52例健康个体血清中IL-17A和IL-17F的水平。
与TC基因型和C等位基因相比，IL-17F TT基因型[比值比（OR）=0.44，95%置信区间（CI）：0.21 - 0.94，P = 0.03]和T等位基因[OR = 0.46，95% CI：0.21 - 1.1，P = 0.03]与CRC风险降低相关。此外，IL-17F TT基因型与肿瘤高分化显著相关（P = 0.02）。我们还观察到，与AA基因型相比，IL-17A G197A SNP的AG基因型与结直肠癌风险增加显著相关（P = 0.001）。与健康个体相比，CRC患者血清中IL-17A浓度显著升高（P = 0.008），且IL-
