Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Cancer Med. 2022 Nov;11(21):3923-3938. doi: 10.1002/cam4.4713. Epub 2022 Apr 4.
Colorectal cancer (CRC) is one of the most common obesity-associated cancers. Inflammation is also considered the most important factor between obesity and CRC. This study aimed to examine miRNAs binding sites variants on inflammatory genes identified using bioinformatics and systematic approach on clinical samples that were collected from CRC patients and controls.
The candidate variants related to CRC inflammatory genes were obtained from genome-wide association studies and their population-specific haplotypes. The variants were analyzed according to their genomic position on the miRNA targetome. Targetome variants in inflammation-related genes were selected for genetic association study by TaqMan genotyping assay.
The GG genotype of rs7473 decreased the risk of obesity (p < 0.05). Heterozygous genotype (GA) of rs1547715 decreased the risk of CRC (p < 0.05). In the rs7473/rs1547715 genotype and haplotype, the frequencies of AA/GA and GG/AA lessened in CRC and obesity, respectively (p < 0.05).
The variants of rs7473 and rs1547715 were associated with obesity and CRC, respectively. The above-mentioned associations could be made based on the interactions of these variants with miRNAs.
结直肠癌（CRC）是最常见的肥胖相关癌症之一。炎症也被认为是肥胖与 CRC 之间最重要的因素。本研究旨在使用生物信息学和系统方法在从 CRC 患者和对照中收集的临床样本中检查炎症基因上的 miRNA 结合位点变异。
从全基因组关联研究及其特定人群的单倍型中获得与 CRC 炎症基因相关的候选变异。根据 miRNA 靶标上的基因组位置分析变异。通过 TaqMan 基因分型检测选择炎症相关基因中的靶标变体进行遗传关联研究。
rs7473 的 GG 基因型降低了肥胖的风险（p<0.05）。杂合基因型（GA）的 rs1547715 降低了 CRC 的风险（p<0.05）。在 rs7473/rs1547715 基因型和单倍型中，AA/GA 和 GG/AA 的频率分别在 CRC 和肥胖中减少（p<0.05）。
rs7473 和 rs1547715 的变异分别与肥胖和 CRC 相关。可以基于这些变体与 miRNAs 的相互作用来建立上述关联。
