Evaluation of SNPs in miR-196-a2, miR-27a and miR-146a as risk factors of colorectal cancer

Abstract

Our data suggest a lack of association between rs11614913, rs895819 and rs2910164 and colorectal cancer risk in the Central-European Caucasian population, a population with an extremely high incidence of sporadic colorectal cancer.

Association Analysis of Single Nucleotide Polymorphisms in miR-146a and miR-196a2 on the Prevalence of Cancer in Elderly Japanese: A Case-Control Study

“…This G to C genetic modification reduces the secondary structure stability, since C has lower free energy (ΔG=-40 kcal/ mol) than G allele (ΔG=-42 kcal/mol) showed reduced mature miR-146a adversely influencing the inhibition of the target tumor suppressor genes such as IL-1 receptorassociated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), and papillary thyroid carcinoma 1 (PTC1), G allele down regulates the mature miR-146a and increased cell proliferation homozygous GG carriers had higher matured miR-146a expression level leading to higher cancer susceptibility (Xu et al, 2008) Furthermore, rs2910164 CC genotype was associated with breast cancer by increasing the binding affinity to BRCA1 and/or BRCA2 oncogenes and alternatively may disturb the wellknown NF-kB apoptotic pathway (Taganov et al, 2006). On the contrary, our results indicated that rs2910164 has no statistical significance with over all cancer which is consistent with previous studies indicating that either rs2910164 (G/C) polymorphism has no significant association or decreasing/protective effect to cancer development (Xu et al, 2013;Xu et al, 2011) even more specifically with liver cancer (Zhou et al, 2011;, colorectal cancer (Hezova et al, 2012, Du et al, 2014, digestive system including gastric cancer (Kupcinskas et al, 2013;Li et al, 2014). The rs11614913 is located the passenger strand of the 3' end of pre-miR-196a2 sequence, which negatively effects the miR-196a2 maturation and its interaction(s) with other miRs or gene(s) and also mature miR-196a2 level was reduced in CC homozygous variant than TT homozygous genotype was found in previous studies (Duan et al, 2008).…”

“…Additionally, Wu et al found no significant association between rs2910164 with digestive cancer (Wu et al, 2013). Hezova et al also found no allelic or genotypic association with rs2910164 and rs11614913 polymorphisms with colorectal cancer in Caucasians (Hezova et al, 2012), Wu et al found no statistical significance These conflicting results deserve more detailed investigation, however there are some possible reasons; first, miR-SNPs in general may affect the incidence of cancer in substantially varied manner in different races and ethnicities, thus both rs2910164 and rs11614913 may have differential results in different ethnical backgrounds; second, most of the previous studies that are indicating the oncogenic implications are meta-analysis which inherently consist of publication, heterogeneity, stratification biases, public vs. hospital based cohort bias and some other calculation/statistical biases may have an accumulated effect on the data analysis (He et al, 2012). Finally, rs2910164 and rs11614913 polymorphism may have unknown target mRNA(s) or gene(s) other than known miR-146a and miR-196a2 eventually, causing differential expression(s) and outcomes in different ethnicities, thus may initiate unidentified pathway(s) leading either tumour suppression or initiation in varying degrees in different types of tissues.…”

“…Recent studies show that rs11614913 may influence lung cancer (Tian et al, 2009;Hong et al, 2011;Yuan et al, 2013), breast cancer (Hoffman et al, 2009;Linhares et al, 2012), head and neck cancer (Christensen et al, 2010), hepatocellular carcinoma (Xu et al, 2008;Qi et al, 2010;Hao et al, 2013), gastric cancer (Peng et al, 2010), prostate cancer (George et al, 2011) and others . On the contrary, there are also several studies for both rs2910164 and rs11614913 polymorphisms indicate conflicting results asserting either lack of association or decreased cancer risk (Xu et al, 2011;Hezova et al, 2012;He et al, 2012;Xu et al, 2013;Zhang et al, 2013). Despite the numerous studies, there is a plausible scientific need to clarify how miR-SNPs such as rs2910164 and rs11614913 effect cancer development or what kind of associations they may have with overall cancer and specific cancer types.…”

Germline miRNA DNA variants and the risk of colorectal cancer by subtype

“…It is notable that the majority of the published studies to date were conducted in Asian populations whereas our study was restricted to Europeans; it is possible these variants are in linkage disequilibrium with an ethnic‐specific risk factor or that our study was underpowered to detect a modest association. Other investigators also report non‐replication of these miRNAs in CRC cohorts of European ancestry (Hezova et al, 2012; Vinci et al, 2013; Kupcinskas et al, 2014). In addition, expression levels for these miRNAs were not reported to differ in CRC across the newly described consensus molecular subtypes of CRC (Guinney et al, 2015).…”

A functional polymorphism rs11614913 in microRNA-196a2 is associated with an increased risk of colorectal cancer although not with tumor stage and grade

“…Previous studies demonstrated that high expression levels of miR-196a2 may promote the migration and invasion of CRC cells and the C allele of rs11614913 polymorphism may affect miR-196a2 expression levels in cancer (13)(14)(15)(16). Several previous studies reported the association between rs11614913 polymorphisms and the susceptibility to CRC (15,(17)(18)(19)(20)(21). However, those studies produced controversial and inconclusive results.…”