miR-449b rs10061133 and miR-4293 rs12220909 polymorphisms are associated with decreased esophageal squamous cell carcinoma in a Chinese population

Abstract

Esophageal cancer is one of the most aggressive cancers in the world, 70% of which are from China and esophageal squamous cell carcinoma (ESCC) is the major histopathological form (>90%). The single nucleotide polymorphisms (SNPs) in mature sequence of microRNA (miRNA) (mmSNPs) could cause the alteration of microRNA expression and contribute to the susceptibility of cancers. To evaluate the association between mmSNPs and ESCC, a case-control study including 773 patients with ESCC and 882 gender- and age-matched controls was carried out to investigate the association of five mmSNPs (miR-449b rs10061133, miR-4293 rs12220909, miR-608 rs4919510, miR-627 rs2620381, and miR-646 rs6513497) with ESCC susceptibility. As a result, two SNPs, miR-449b rs10061133 and miR-4293 rs12220909, were associated with decreased ESCC risk. For miR-449b rs10061133 A>G, individuals carrying GG genotype had an odds ratio (OR) of 0.77 (95% confidence interval (95% CI) 0.62-0.97) compared with individuals with AA genotype. In the recessive model, the GG genotype also showed a protective effect on ESCC (OR = 0.78, 95% CI 0.63-0.97). For miR-4293 rs12220909 G>C, the heterozygous genotype GC was associated with a decreased ESCC risk (OR = 0.77, 95% CI 0.61-0.97) compared with GG genotype. The C allele conferred 23% decrease in ESCC risk compared with the G allele in the allelic model (95% CI 0.63-0.93). In the dominant model, the GC/CC genotypes decreased the risk of ESCC (adjusted OR = 0.77, 95% CI 0.61-0.96). This study provides the first evidence that miR-449b rs10061133 and miR-4293 rs12220909 are associated with ESCC risk in Chinese population.

Impact and Evolutionary Determinants of Neanderthal Introgression on Transcriptional and Post-Transcriptional Regulation

“…For example, the archaic allele at miR-4293 (rs12220909) is responsible for the loss of 95% of its targets and has been associated with diminished cancer susceptibility. 43,44 Archaic introgression has also affected miRNA binding sites, as illustrated by ONECUT2 (MIM: 604894), where an archaic haplotype that is present at a high frequency in Asia (MAF CHB ¼ 0.49) alters multiple conserved miRNA binding sites. ONECUT2 is involved in liver, pancreas, and nervous-system development 45 and has recently been proposed as a regulator of tumor growth in ovarian cancer (MIM: 167000).…”

Genetic variant of miR-4293 rs12220909 is associated with susceptibility to non-small cell lung cancer in a Chinese Han population

“…Additionally, it has been determined that this genetic polymorphism significantly decreases risk of esophageal squamous cell carcinoma (OR = 0.77, 95%CI = 0.61–0.97) [17]. However, the potential influence of the rs12220909 G>C genetic polymorphism in miR-4293 on NSCLC susceptibility has not been analyzed.…”

“…It was first reported by Gong et al[16] that rs12220909 was the only SNP loci located in the miR-4293 seed region. It has been demonstrated that the genetic polymorphism decreased esophageal squamous cell carcinoma risk [17]. However, there were no studies that focused on the association between miR-4293 rs12220909 and NSCLC risk in the Chinese Han population.…”

“…According to Gene Ontology and KEGG analysis results, the SNP loci rs12220909G>C not only changes the ability of miR-4293 to combine with target genes, it also alters the quantity and types of target genes miR-4293 acts upon. Additionally, it has been shown that this miR-4293 genetic polymorphism can decrease the risk of esophageal squamous cell carcinoma [17]. Nonetheless, the potential influence of rs12220909 G>C in miR-4293 on the susceptibility to NSCLS has not yet been analyzed.…”

Associations between genetic variants located in mature microRNAs and risk of lung cancer

“…Genetic variants located in Mature MicroRNAs have been also explored to discover potential clues for pathogenesis of many diseases [24–30]. Recently, Zhang et al [29] evaluated five SNPs in the mature sequence of microRNAs, and found miR-449b rs10061133 and miR-4293 rs12220909 polymorphisms are associated with decreased esophageal squamous cell carcinoma. Qiu et al [25] evaluated 8 SNPs in the mature sequence of microRNAs, and the results showed that rs4919510 in mature mir-608 sequence is associated with an increased risk of nasopharyngeal carcinoma.…”