基因的微小RNA（miRNA）hsa-miR21和hsa-miR590结合位点中的单核苷酸多态性rs4648298是结直肠癌的一个重要决定因素。
Single nucleotide polymorphism rs4648298 in miRNAs hsa-miR21 and hsa-miR590 binding site of gene is a strong colorectal cancer determinant.
作者信息
Mosallaei Meysam, Simonian Miganoosh, Ahangari Fateme, Miraghajani Maryam, Mortazavi Deniz, Salehi Ahmad Reza, Khosravi Sharifeh, Salehi Rasoul
机构信息
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
出版信息
J Gastrointest Oncol. 2018 Jun;9(3):448-457. doi: 10.21037/jgo.2017.11.01.
BACKGROUND
Genetic determinants are considered as driving forces in development colorectal cancer (CRC), a malignancy that ranks as the second cause of cancer death in the world. Single nucleotide polymorphisms (SNPs), are considered as the main genetic factor in cancers susceptibility. MicroRNAs are critical players in posttranslational gene regulation by binding to their specific recognition sequences located at 3' untranslated region (UTR) of mRNAs. In present study we have elucidated the role of 9,850 A > G (rs4648298), in development of sporadic CRC in Iranian population.
METHODS
A case-control study using 88 CRC patients and 88 noncancerous counterparts was undertaken in order to determine rs4648298 genotypes using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Also, a meta-analysis was performed based on 9 articles accessed via the MEDLINE, Cochrane review, Google Scholar and Scopus databases.
RESULTS
AA genotype was determined to be associated with significant decreased risk of CRC in our study population [odds ratio (OR) =0.14; 95% confidence interval (CI), 0.05-0.34; P<0.001]. In a meta-analysis on 6 risk estimates for the AG versus AA genotype, we found a significant inverse association between AG SNPs and risk of gastric adenocarcinoma, CRC, breast cancer and prostate cancer (OR =0.86; 95% CI, 0.76-0.98; P<0.02).
CONCLUSIONS
Our results suggest significant correlation between rs4648298 polymorphism and CRC risk in Iranian population.
背景
遗传决定因素被认为是结直肠癌（CRC）发生发展的驱动力，结直肠癌是全球癌症死亡的第二大原因。单核苷酸多态性（SNP）被认为是癌症易感性的主要遗传因素。微小RNA通过与位于mRNA 3'非翻译区（UTR）的特定识别序列结合，在翻译后基因调控中起关键作用。在本研究中，我们阐明了9,850 A > G（rs4648298）在伊朗人群散发性结直肠癌发生发展中的作用。
方法
采用病例对照研究，选取88例结直肠癌患者和88例非癌对照，使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法确定rs4648298基因型。此外，基于通过MEDLINE、Cochrane综述、谷歌学术和Scopus数据库获取的9篇文章进行了荟萃分析。
结果
在我们的研究人群中，确定AA基因型与结直肠癌风险显著降低相关[比值比（OR）=0.14；95%置信区间（CI），0.05 - 0.34；P<0.001]。在对AG与AA基因型的6个风险估计值进行的荟萃分析中，我们发现AG SNP与胃腺癌、结直肠癌、乳腺癌和前列腺癌风险之间存在显著的负相关（OR =0.86；95% CI，0.76 - 0.98；P<0.02）。
结论
我们的结果表明rs4648298多态性与伊朗人群结直肠癌风险之间存在显著相关性。
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