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MicroRNA biogenesis pathway genes polymorphisms and cancer risk: a systematic review and meta-analysis.

ABSTRACT: MicroRNAs (miRNAs) may promote the development and progression of human cancers. Therefore, components of the miRNA biogenesis pathway may play critical roles in human cancer. Single nucleotide polymorphisms (SNPs) or mutations in genes involved in the miRNA biogenesis pathway may alter levels of gene expression, affecting disease susceptibility. Results of previous studies on genetic variants in the miRNA biogenesis pathway and cancer risk were inconsistent. Therefore, a meta-analysis is needed to assess the associations of these genetic variants with human cancer risk. We searched for relevant articles from PubMed, Web of Science, CNKI, and CBM through Jun 21, 2016. In total, 21 case-control articles met all of the inclusion criteria for the study. Significant associations were observed between cancer risk and the DGCR8polymorphism rs417309 G >A (OR 1.22, 95% CI [1.04-1.42]), as well as the DICER1 polymorphism rs1057035 TT (OR 1.13, 95% CI [1.05-1.22]). These SNPs exhibit high potential as novel diagnostic markers. Future studies with larger sample sizes and more refined analyses are needed to shed more light on these findings.

SUBMITTER: He J

PROVIDER: S-EPMC5147022 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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MicroRNA biogenesis pathway genes polymorphisms and cancer risk: a systematic review and meta-analysis.

He Jieyu J Zhao Jun J Zhu Wenbo W Qi Daxun D Wang Lina L Sun Jinfang J Wang Bei B Ma Xu X Dai Qiaoyun Q Yu Xiaojin X

PeerJ 20161207

MicroRNAs (miRNAs) may promote the development and progression of human cancers. Therefore, components of the miRNA biogenesis pathway may play critical roles in human cancer. Single nucleotide polymorphisms (SNPs) or mutations in genes involved in the miRNA biogenesis pathway may alter levels of gene expression, affecting disease susceptibility. Results of previous studies on genetic variants in the miRNA biogenesis pathway and cancer risk were inconsistent. Therefore, a meta-analysis is needed ...[more]

PMID: 27957388

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Project description:MicroRNAs (miRNAs) have been implicated in the incidence and progression of cancer. It has been proposed that single nucleotide polymorphisms (SNPs) influence cancer risk due to their position within genes involved in miRNA synthesis and regulation.Genes directly and indirectly involved in miRNA biogenesis were identified from the literature. We then identified SNPs within these regions. Using genome-wide association study data we evaluated associations between biogenesis-related SNPs with colon cancer risk and their corresponding mRNA expression in normal colonic mucosa and carcinoma and difference in expression between the two tissues. SNPs that were associated with either altered colon cancer risk or with mRNA expression were evaluated for associations with altered miRNA expression.Eleven SNPs were associated (P?<?0.05) with colon cancer risk, and two of these variants remained significant after correction for multiple comparisons (PHolm?<?0.05): rs1967327 (PRKRA) (ORdom?=?0.78, 95 % CI 0.66-0.92) and rs4548444 (MAPKAP2) (ORrec?=?1.67, 95 % CI 1.12-2.48). Of these two SNPs, rs4548444 (MAPKAP2), was associated with significantly altered miRNA expression levels in normal colonic mucosa, with nine miRNAs upregulated among individuals homozygous rare (GG) for rs4548444. One SNP associated with cancer prior to adjustment for multiple comparisons, rs11089328 (DGCR8), was associated with altered levels of hsa-miR-645 in differential tissue under the dominant model. Three SNPs, rs2740349 (GEMIN4) in carcinoma tissue, and rs235768 (BMP2) and rs2059691 (PRKRA) in normal mucosa, were significantly associated with altered mRNA expression levels across genotypes after multiple comparison adjustment. Rs2740349 (GEMIN4) and rs235768 (BMP2) were significantly associated with the upregulation of six and nine individual miRNAs in normal colonic mucosa, respectively.Our data suggest that few of the SNPs in biogenesis genes we evaluated alter levels of mRNA transcription or colon cancer risk. As only one SNP both alters colon cancer risk and miRNA expression it is likely that SNPs influencing cancer do not do so through miRNAs. Because the significant SNPs were associated with downregulated mRNAs and upregulated miRNAs, and because each SNP was associated with unique miRNAs, it is possible that other mechanisms influence mature miRNA levels.

Dataset Information

MicroRNA biogenesis pathway genes polymorphisms and cancer risk: a systematic review and meta-analysis.

Publications

MicroRNA biogenesis pathway genes polymorphisms and cancer risk: a systematic review and meta-analysis.

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