A miRNA-binding site single nucleotide polymorphism in the 3′-UTR region of the NOD2 gene is associated with colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the common malignancies worldwide. Single nucleotide polymorphisms in miRNA-binding site on gene transcripts are reported to play important role in increased risk of CRC in different population. We performed a case-control study using 88 CRC patients and 88 non-cancer counterparts to evaluate the association between NOD2 rs3135500 polymorphism located at 3' untranslated region of the gene and risk of sporadic CRC. Genotyping of rs3135500 polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We found a significant association of AA genotype with risk of CRC (adjusted OR 3.100, CI 1.621-5.930, p < 0.001). Also, significant difference in physical activity (p = 0.001) between case and control groups was found. We also found that individuals in control group were more aspirin or NSAID user compared to sporadic CRC cases (p = 0.002). In the case group, individuals with GG genotype consumed more aspirin or NSAID compared with AA+AG genotypes (33.3 vs. 9.6 %, adjusted OR 4.71, CI 1.25-17.76, p = 0.02). However, in the control group, individuals with AA+AG genotypes used more aspirin or NSAID compared with GG genotypes (47.2 vs. 11.4 %, adjusted OR 14 %, CI 0.05-0.47, p < 0.001).

Functional Variant rs3135500 in NOD2 Increases the Risk of Multiple System Atrophy in a Chinese Population

“…All of which suggested that chronic inflammation mediated by possible abnormal NOD2 by the encoding variants might be involved in the etiology of neurodegenerative diseases (Li et al, 2016 ). In the current study, SNP rs3135500 in the 3′-UTR of NOD2 was found to increase the risk for MSA, which has been reported to increase the risk of CRC in an Iran study (Ahangari et al, 2014 ). Combination with previous study (Bialecka et al, 2007 ), our data may provide new evidence supporting similar pathogenic mechanisms mediated by NOD2 for both MSA and PD.…”

“…The frequencies of the P268S, R702W, G908R, 1007fs, and rs3135500 polymorphisms of NOD2 were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Primer sequences and restriction enzymes were used according to published studies (Ma et al, 2013 ; Ahangari et al, 2014 ). The RFLP results were confirmed by direct sequencing of the PCR products (Tsingke, Chengdu, China).…”

“…Recently, variants including P268S, R702W, G908R, and 1007fs in the nucleotide-binding oligomerization domain protein 2 ( NOD2 ) gene, encoding the NF- κB-mediated inflammation related protein NOD-2, were found to be associated with PD in Polish or Chinese patient populations (Bialecka et al, 2007 ; Ma et al, 2013 ). Additionally, a miRNA-binding variant in the 3′-UTR of the NOD2 gene, rs3135500, which may modify miRNA-mRNA binding and alter target gene regulation, was reported to be related to another gastrointestinal tract disease in which inflammatory is an important risk factor, colorectal cancer (CRC), in Iranian (Ahangari et al, 2014 ). One of the current hotspot theory leading to PD is that the neuropathological process appears to start in the gut and spreads to the substantia nigra and the central nervous system (CNS) (Klingelhoefer and Reichmann, 2015 ), indicating that PD and gastrointestinal diseases may have a similar genetic basis.…”

The association of nucleotide‐binding oligomerization domain 2 gene polymorphisms with the risk of asthma in the Chinese Han population

“…A research reported that the NOD2 gene rs2066842 and rs2066843 polymorphisms showed a significant association with ulcerative colitis, but not with Crohn's in Indian patients (Pugazhendhi, Santhanam, Venkataraman, Creveaux, & Ramakrishna, ). Ahangari, Salehi, Salehi, & Khanahmad () showed that the rs3135500 AA genotype had a significant association with risk of Colorectal cancer in the Iran population. The research data of Cao et al.…”

Polymorphism (rs16917496) at the miR-502 Binding Site of the Lysine Methyltransferase 5A (SET8) and its Correlation with Colorectal Cancer in Iranians

“…MicroRNAs (miRNAs) constitute a novel discovered a class of small noncoding RNAs (about 22 nucleotides long) that play important roles in posttranscriptional gene regulation by binding to the 3’-untranslated regions (3’-UTRs) of specific mRNAs resulting in mRNA cleavage or translational repression. [ 4 14 15 16 ] SNPs located in miRNAs-binding sites contribute to the disruption of miRNA recognition elements (MREs) or create new sites which eventually can lead to gene expression dysregulation and disease susceptibility. [ 2 17 18 ]…”