Banday Mujeeb Z, Sameer Aga S, Chowdri Nissar A, Haq Ehtishamul
aDepartment of Biotechnology, University of Kashmir bDepartment of Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India cDepartment of Basic Medical Sciences, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Eur J Cancer Prev. 2017 Nov;26(6):476-490. doi: 10.1097/CEJ.0000000000000370.
Chronic inflammation influences the development of various cancers including colorectal cancer (CRC). Interleukin-10 (IL-10), an anti-inflammatory cytokine, plays a vital role in several homeostatic physiological processes occurring in the human gastrointestinal tract including intestinal inflammation and is a key regulator of several gastrointestinal tract pathophysiological processes such as inflammatory bowel diseases that are associated with an increased predisposition to CRC. Several studies have reported the association of various polymorphisms in the human IL-10 gene including IL-10 -592C/A and IL-10 -1082A/G single nucleotide polymorphisms (SNPs) with various cancers including CRC, but these SNPs are yet to be studied in a Kashmiri population with respect to CRC risk. The aim of this study was to analyze the association of IL-10 -592C/A and IL-10 -1082A/G promoter SNPs with CRC risk in an ethnic Kashmiri population through a case-control design. The genotype frequencies of IL-10 -592C/A and IL-10 -1082A/G promoter SNPs were compared between 142 CRC patients and 184 individually matched healthy controls using the PCR and restriction fragment length polymorphism method. The association between the IL-10 -592C/A and IL-10 -1082A/G SNPs and CRC risk was examined through conditional logistic regression models adjusted for multiple possible confounding (third) variables. The possible effect measure modification of the association between the relevant SNP genotypes and CRC risk by various CRC risk factors including age, sex, and smoking status was also evaluated. Further, the associations between these SNPs and various clinicopathological parameters, demographic variables, and environmental factors in the case group patients with respect to CRC risk were also analyzed. The overall association between the IL-10 -592C/A SNP and the modulation of CRC risk was found to be significant (P=0.001). The variant genotype (AA) was significantly associated with a decreased risk of CRC (odds ratio: 0.25; 95% confidence interval: 0.11-0.61; P=0.002). Further, the less common IL-10 -592A allele was associated with a decreased risk of CRC (odds ratio: 0.64; 95% confidence interval: 0.46-0.88; P=0.0092). The overall association between the IL-10 -1082A/G SNP and the modulation of CRC risk was not found to be significant (P=0.141). This study has shown that there is a significant association between the IL-10 -592C/A promoter SNP and a decreased risk of CRC in an ethnic Kashmiri population, but the association between IL-10 -1082A/G SNP and the risk of CRC in the population under study is not significant. However, to substantiate our findings, this study needs to be replicated with a larger sample size and with other ethnically defined populations with comparable CRC incidence.
慢性炎症会影响包括结直肠癌（CRC）在内的多种癌症的发展。白细胞介素-10（IL-10）是一种抗炎细胞因子，在人体胃肠道发生的多种稳态生理过程（包括肠道炎症）中发挥着至关重要的作用，并且是多种胃肠道病理生理过程（如与患CRC易感性增加相关的炎症性肠病）的关键调节因子。多项研究报告了人类IL-10基因中的各种多态性，包括IL-10 -592C/A和IL-10 -1082A/G单核苷酸多态性（SNP）与包括CRC在内的各种癌症之间的关联，但在克什米尔人群中，尚未针对CRC风险对这些SNP进行研究。本研究的目的是通过病例对照设计，分析IL-10 -592C/A和IL-10 -1082A/G启动子SNP与克什米尔族人群CRC风险之间的关联。使用聚合酶链反应（PCR）和限制性片段长度多态性方法，比较了142例CRC患者和184例个体匹配的健康对照中IL-10 -592C/A和IL-10 -1082A/G启动子SNP的基因型频率。通过针对多个可能的混杂（第三）变量进行调整的条件逻辑回归模型，研究了IL-10 -592C/A和IL-10 -1082A/G SNP与CRC风险之间的关联。还评估了包括年龄、性别和吸烟状况在内的各种CRC风险因素对相关SNP基因型与CRC风险之间关联的可能效应修正。此外，还分析了这些SNP与病例组患者中与CRC风险相关的各种临床病理参数、人口统计学变量和环境因素之间的关联。发现IL-10 -592C/A SNP与CRC风险调节之间的总体关联具有统计学意义（P = 0.001）。变异基因型（AA）与CRC风险降低显著相关（优势比：0.25；95%置信区间：0.11 - 0.61；P = 0.002）。此外，较罕见的IL-10 -592A等位基因与CRC风险降低相关（优势比：0.64；95%置信区间：0.46 - 0.88；P = 0.0092）。未发现IL-10 -1082A/G SNP与CRC风险调节之间的总体关联具有统计学意义（P = 0.14）。本研究表明，在克什米尔族人群中，IL-10 -592C/A启动子SNP与CRC风险降低之间存在显著关联，但在本研究人群中，IL-10 -1082A/G SNP与CRC风险之间的关联不显著。然而，为了证实我们的发现，本研究需要在更大样本量以及其他CRC发病率相当的不同种族人群中进行重复研究。
