Rs895819 within miR-27a Might be Involved in Development of Non Small Cell Lung Cancer in the Chinese Han Population

Abstract

MicroRNA-27a (miR-27a) is deemed to be an oncogene that plays an important role in development of various cancers, and single nucleotide polymorphism (SNP) of miR-27a can influence the maturation or aberrant expression of hsa-miR27a, resulting in increased risk of cancer and poor prognosis for non-small cell lung cancer (NSCLC). This study aimed to assess the effects of rs895819 within miR-27a on susceptibility and prognosis of NSCLC patients in 560 clinical confirmed cases and 568 healthy check-up individuals. Adjusted odds/hazard ratios (ORs/HRs) and 95% confidential intervals (CIs) were calculated to evaluate the association between rs895819 and the risk and prognosis of NSCLC. The results showed that allele A and genotype GG of rs895819 were significantly associated with an increased risk of NSCLC (38.9% vs 30.8%, adjusted OR=1.26, 95%CI=1.23-1.29 for allele G vs A; 18.1% vs 11.7%, adjusted OR=1.67, 95%CI=1.59-1.75 for genotype GG vs AA). Moreover, positive associations were also observed in dominant and recessive models (53.7% vs 49.9%, adjusted OR=1.17, 95%CI=1.13-1.20 for GG/AG vs AA; 18.1% vs 11.7%, adjusted=1.65, 95%CI=1.58-1.73). However, no significant association was found between rs895819 and the prognosis of NSCLC in genotype, dominant and recessive models. These results suggested that miR-27a might be involved in NSCLC carcinogenesis, but not in progression of NSCLC. The allele G, genotype GG and allele G carrier (GG/AG vs AA) of rs895819 might be genetic susceptible factors for NSCLC. Further multi-central, large sample size and well-designed prospective studies as well as functional studies are warranted to verify our findings.

Systematic evaluation of cancer risk associated with rs2292832 in miR-149 and rs895819 in miR-27a: a comprehensive and updated meta-analysis

“…After further identification and screening individual study, 43 articles (49 studies) [11–53] underwent full-text assessment, and 6 articles (10 studies, not including one site according to HWE) [14, 17, 19, 20, 35, 42] were excluded due to inconsistently with HWE. Finally, 37 articles (40 studies) [11–13, 15, 16, 18, 21–34, 36–41, 43–53] were conducted in quantitative synthesis.…”

MicroRNAs and Drinking: Association between the Pre-miR-27a rs895819 Polymorphism and Alcohol Consumption in a Mediterranean Population

“…There are previous studies that have consistently shown that this polymorphism is functional, and the variant G allele is associated with higher levels of miR27a [34,35]. Likewise, there are also several previous studies that have associated this polymorphism with a greater risk of cancer [34,35,36,50,51]. Interestingly, many of those cancers are related to alcohol consumption (gastric, colorectal, lung, etc.)…”

Evaluation of miR-27a, miR-181a, and miR-570 Genetic Variants with Gallbladder Cancer Susceptibility and Treatment Outcome in a North Indian Population

“…We observed that genetic risk by miR-27a (rs895819) (A[G) was also modulated by tobacco consumption as the heterozygotes (AG) were at higher risk. Previously, polymorphisms in the miR-27a gene have been recognized as being involved in the pathogenesis, metastasis, and invasion of multiple cancer types (e.g., gastric, nonsmall-cell lung, colorectal, pancreatic, and breast cancer) by functioning as an oncogene via complex mechanisms [24,28,29,37]. This suggests that variants in miR-27a may affect GBC susceptibility in specific subgroups.…”

“…We selected three functional SNPs, miR-27a (rs895819), miR-570 (rs4143815), and miR-181a (rs12537), for this study on the basis of their stabilized role in various other cancers [24][25][26][27][28][29][30][31] and their established targets in cancer-related genes. The minor allele frequency (MAF) of all the above SNPs followed GIH Hapmap data, and all controls followed Hardy Weinberg equilibrium (HWE).…”

“…The function of miRNA polymorphisms in cancers has been explored in many studies, including nonsmall-cell lung cancer (NSCLC) [20], papillary thyroid carcinoma [21], hepatocellular carcinoma [22], and bladder cancer [23]. Recently, polymorphisms in miR-27a (rs895819), miR-570 (rs4143815), and miR-181a (rs12537) altering miRNA processing and expression have been extensively studied in various cancers [24][25][26][27][28][29][30][31]. Some of these target genes include V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), ras-related protein (RAP1B), ribosomal protein S6 kinase (RPS6KA3), mitogen-activated protein kinase kinase 1 (MAP2K1), protein phosphatase 2B regulatory subunit 1 (PPP3R1) [regulated by miR-181a], forkhead box (FOX1), KRAS, MAP2K7, MAP2K4, MAP3K4, [targets genes of miR-27a], KRAS, G1/S-specific cyclin-D3 (CCND3), CCND2, cAMP-response element-binding protein (CREBBP), serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform (PPP3CC), phosphatase and tensin homolog (PTEN) [target genes of miR-570] (http://bioinfo.…”