• gene polymorphism
• meta-analysis
• non-coding rnas
• ovarian cancer risk

• Female
• Humans
• Reproducibility of Results
• Genetic Predisposition to Disease
• MicroRNAs/genetics
• Polymorphism, Single Nucleotide
• Ovarian Neoplasms/genetics
• Case-Control Studies

Type 2 diabetes mellitus (T2DM) has been confirmed to be closely associated with breast cancer (BC). However, the shared mechanisms between these diseases remain unclear. By comparing different datasets, we identified shared differentially expressed (DE) RNAs in T2DM and BC, including 427 mRNAs and 6 miRNAs from the GEO(Gene Expression Omnibus) database. We used databases to predict interactions to construct two critical networks. The transcription factor (TF)-miRNA‒mRNA network contained 236 TFs, while the RNA binding protein (RBP)-pseudogene-mRNA network showed that the pseudogene S-phase kinase associated protein 1 pseudogene 1 (SKP1P1) might play a key role in regulating gene expression. The shared mRNAs between T2DM and BC were enriched in cytochrome (CYP) pathways, and further analysis of CPEB1 and COLEC12 expression in cell lines, single cells and other cancers showed that they were strongly correlated with the survival and prognosis of patients with BC. This result suggested that patients with T2DM presenting the downregulation of CPEB1 and COLEC12 might have a higher risk of developing BC. Overall, our work revealed that high expression of CYPs in patients with T2DM might be a susceptibility factor for BC and identified novel gene candidates and immune features that are promising targets for immunotherapy in patients with BC.

• Breast Neoplasms/genetics
• Cytochromes/genetics
• Cytochromes/metabolism
• Diabetes Mellitus, Type 2/genetics
• Female
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Pseudogenes
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• RNA-Binding Proteins/metabolism
• S-Phase Kinase-Associated Proteins/genetics
• S-Phase Kinase-Associated Proteins/metabolism
• Transcription Factors/genetics
• Transcription Factors/metabolism

• Association studies
• Breast cancer risk
• Polymorphisms
• miRNAs

• Single nucleotid polymorphism (SNP)
• Tetra ARMS PCR
• breast cancer
• miR146a gene
• rs2910164

• Base Sequence
• Biomarkers, Tumor/genetics
• Breast Neoplasms/epidemiology
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Case-Control Studies
• Female
• Follow-Up Studies
• Genetic Predisposition to Disease
• Humans
• Iran/epidemiology
• MicroRNAs/genetics
• Middle Aged
• Polymorphism, Single Nucleotide
• Prognosis

Breast (BCa) and gynecological (GCa) cancers constitute a group of female neoplasms that has a worldwide significant contribution to cancer morbidity and mortality. Evidence suggests that polymorphisms influencing miRNA function can provide useful information towards predicting the risk of female neoplasms. Inconsistent findings in the literature should be detected and resolved to facilitate the genetic screening of miRNA polymorphisms, even during childhood or adolescence, and their use as predictors of future malignancies. This study represents a comprehensive systematic review and meta-analysis of the association between miRNA polymorphisms and the risk of female neoplasms. Meta-analysis was performed by pooling odds-ratios (ORs) and generalized ORs while using a random-effects model for 15 miRNA polymorphisms. The results suggest that miR-146a rs2910164 is implicated in the susceptibility to GCa. Moreover, miR-196a2 rs11614913-T had a moderate protective effect against female neoplasms, especially GCa, in Asians but not in Caucasians. MiR-27a rs895819-G might pose a protective effect against BCa among Caucasians. MiR-499 rs3746444-C may slightly increase the risk of female neoplasms, especially BCa. MiR-124 rs531564-G may be associated with a lower risk of female neoplasms. The current evidences do not support the association of the remaining polymorphisms and the risk of female neoplasms.

• breast neoplasm
• cancer
• female neoplasm
• microRNA
• polymorphism
• susceptibility

• Asian People
• Breast Neoplasms/epidemiology
• Breast Neoplasms/genetics
• Female
• Genetic Association Studies
• Genetic Predisposition to Disease
• Genital Neoplasms, Female/epidemiology
• Humans
• MicroRNAs/genetics
• Polymorphism, Single Nucleotide/genetics
• Risk

• South American population
• familial breast cancer
• microRNA
• polymorphisms

• 146a(rs2910164)
• 196a2(rs11614913)
• breast cancer
• microRNA(miRNA)
• polymorphism

Several studies have evaluated the association of miR-146a C/G with head and neck cancer (HNC) susceptibility, and overall cancer risk, but with inconclusive outcomes. To drive a more precise estimation, we carried out this meta-analysis. The literature was searched from MEDLINE (mainly PubMed), Embase, the Cochrane Library, and Google Scholar databases to identify eligible studies. A total of 89 studies were included. The results showed that miR-146a C/G was significantly associated with increased HNC risk in dominant model (I² =15.6%, P_{heterogeneity}=0.282, odds ratio (OR) =1.088, 95% confidence interval (CI) =1.002–1.182, P=0.044). However, no cancer risk was detected under all genetic models. By further stratified analysis, we found that rs4919510 mutation contributed to the risk of HNC amongst Asians under homozygote model (I² =0, P_{heterogeneity}=0.541, OR =1.189, 95% CI =1.025–1.378, P=0.022), and dominant model (I² =0, P_{heterogeneity}=0.959, OR =1.155, 95% CI =1.016–1.312, P=0.028). Simultaneously, in the stratified analysis by source of controls, a significantly increased cancer risk amongst population-based studies was found under homozygote model, dominant model, recessive model, and allele comparison model. However, no significant association was found in the stratified analysis by ethnicity and source of control. The results indicated that miR-146a C/G polymorphism may contribute to the increased HNC susceptibility and could be a promising target to forecast cancer risk for clinical practice. However, no significant association was found in subgroup analysis by ethnicity and source of control. To further confirm these results, well-designed large-scale case–control studies are needed in the future.

• cancer risk
• head and neck cancer
• meta-analysis
• miR-146a C/G
• polymorphism

Three functional microRNA polymorphisms (miR-499 rs3746444 A > G, miR-196a rs11614913 C > T and miR-146a rs2910164 G > C) have been reported to be associated with breast cancer (BC) risk. However, the results of the published studies are inconsistent. In order to obtain a more credible result, we conducted this meta-analysis. We searched PubMed, EMBASE and Web of Science databases to identify relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association. Thirty-eight eligible studies with 17,417 cases and 18,988 controls were included in this meta-analysis. Our results showed that the rs3746444 was associated with an increased breast cancer risk in the four genetic models (G vs. A: OR = 1.17, P = 0.008; GG vs. AA: OR = 1.41, P < 0.001; AG vs. AA: OR = 1.10, P = 0.036; GG+AG vs. AA: OR = 1.16, P = 0.001). In the subgroup analysis by ethnicity, significant correlation remained in Asians but not in Caucasians. For rs11614913, obvious decreased breast cancer risk was observed in Caucasian populations (T vs. C: OR = 0.93, P = 0.044). However, we couldn't detect an association between rs2910164 and breast cancer risk. This meta-analysis demonstrates that rs3746444 could increase breast cancer risk in Asians and in general populations, while rs11614913 could decrease the risk of breast cancer in Caucasians. The rs2910164 polymorphism has no association with breast cancer risk. More multicenter studies with larger sample sizes are required to verify our results.

• breast cancer
• meta-analysis
• rs11614913
• rs2910164
• rs3746444

• endocrine cancers
• thyroid

• breast cancer
• meta-analysis
• miRNA
• polymorphisms

MicroRNAs (miRNAs) are a novel class of endogenous, non-coding, single-stranded RNAs capable of regulating gene expression by suppressing translation or degrading mRNAs. Single nucleotide polymorphisms (SNP) can alter miRNA expression, resulting in diverse functional consequences. Previous studies have examined the association of miRNA SNPs with breast cancer (BC) susceptibility. The contribution of miRNA gene variants to BC susceptibility in South American women had been unexplored. Our study evaluated the association of the SNPs rs895819 in pre-miR27a, rs11614913 in pre-miR-196a2, rs6505162 in pre-miR-423, rs4919510 in miR-608, and rs2682818 in pre-mir-618 with familial BC and early-onset non-familial BC in non-carriers of BRCA1/2 mutations from a South American population.

We evaluated the association of five SNPs with BC risk in 440 cases and 807 controls. Our data do not support an association of rs11614913:C > T and rs4919510:C > G with BC risk. The rs6505162:C > A was significantly associated with increased risk of familial BC in persons with a strong family history of BC (OR = 1.7 [95 % CI 1.0–2.0] p = 0.05). The rs2682818:C > A genotype C/A is associated with an increased BC risk in non-familial early-onset BC. For the rs895819:A > G polymorphism, the genotype G/G is significantly associated with reduced BC risk in families with a moderate history of BC (OR = 0.3 [95 % CI 0.1–0.8] p = 0.01).

The contribution of variant miRNA genes to BC in South American women had been unexplored. Our findings support the following conclusions: a) rs6505162:C > A in pre-miR-423 increases risk of familial BC in families with a strong history of BC; b) the C/A genotype at rs2682818:C > A (pre-miR-618) increases BC risk in non-familial early-onset BC; and c) the G/G genotype at rs895819:A > G (miR-27a) reduces BC risk in families with a moderate history of BC.

• Familial breast cancer
• MicroRNA
• Polymorphisms
• South American population

• BRCA
• Breast cancer
• Polymorphism
• SNP
• miR146a
• miRNA

MicroRNAs (miRNAs) are small non-coding RNA molecules, which participate in diverse biological processes and may regulate tumor suppressor genes or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to diverse functional consequences, including cancer development, by altering miRNA expression. Numerous studies have shown the association between miRNA SNPs and cancer risk; however, the results are generally debatable and inconclusive, mainly due to limited statistical power. To assess the relationship between the five most common SNPs (miR-146a rs2910164, miR-196a2 rs11614913, miR-499 rs3746444, miR-149 rs2292832, and miR-27a rs895919) and the risk cancer development, we performed a meta-analysis of 66 published case-control studies. Crude odds ratios at 95% confidence intervals were used to investigate the strength of the association. No association was observed between rs2910164 and cancer risk in the overall group. However, in stratified analysis, we found that either the rs2910164 C allele or the CC genotype was protective against bladder cancer, prostate cancer, cervical cancer, and colorectal cancer, whereas it was a risk factor for papillary thyroid carcinoma and squamous cell carcinoma of the head and neck (SCCHN). Further, rs11614913 was found to be significantly associated with decreased cancer risk, in particular, for bladder cancer, gastric cancer, and SCCHN. For miR-499, a significant association was found between the rs3746444 polymorphism and cancer risk in pooled analysis. In subgroup analysis, similar results were mainly observed for breast cancer. Finally, no association was found between rs2292832 and rs895919 polymorphisms and cancer risk in the overall group and in stratified analysis. In summary, miR-196a2 rs11614913, miR-146a rs2910164, and miR-499 rs3746444 are risk factors for cancer development, whereas mir-149 rs2292832 and miR-27a rs895919 are not associated with cancer risk.

• Breast Neoplasms/genetics
• Carcinoma/genetics
• Carcinoma, Papillary
• Carcinoma, Squamous Cell/genetics
• Case-Control Studies
• Female
• Genetic Predisposition to Disease/genetics
• Genotype
• Head and Neck Neoplasms/genetics
• Humans
• Male
• MicroRNAs/genetics
• Polymorphism, Single Nucleotide/genetics
• Prostatic Neoplasms/genetics
• Squamous Cell Carcinoma of Head and Neck
• Stomach Neoplasms/genetics
• Thyroid Cancer, Papillary
• Thyroid Neoplasms/genetics
• Urinary Bladder Neoplasms/genetics

Previous studies have investigated the association between single nucleotide polymorphisms (SNPs) located in microRNAs (miRNAs) and breast cancer susceptibility; however, because of their limited statistical power, many discrepancies are revealed in these studies. The meta-analysis presented here aimed to identify and characterize the roles of miRNA SNPs in breast cancer risk, and evaluate the associations of polymorphisms in miR-146a rs2910164, miR-196a rs11614913 and miR-499 rs3746444 with breast cancer susceptibility, respectively.

The PubMed and Embases databases were searched updated to 31^st December, 2012. The complete data of polymorphisms in miR-146a rs2910164, miR-196a rs11614913 and miR-499 rs3746444 from case-control studies for breast cancer were analyzed by odds ratios (ORs) with 95% confidence intervals (CIs) to reveal the associations of SNPs in miRNAs with breast cancer susceptibility. Totally, six studies for rs2910164 in miR-146a, involving 4225 cases and 4469 controls; eight studies for rs11614913 in miR-196a, involving 4110 cases and 5100 controls; and three studies of rs3746444 in miR-499, involving 2588 cases and 3260 controls, were investigated in the meta-analysis. The rs11614913 (TT+CT) genotype of miR-196a2 was revealed to be associated with a decreased breast cancer susceptibility compared with the CC genotypes (OR = 0.906, 95% CI: 0.825–0.995, P = 0.039); however, no significant associations were observed between rs2910164 in miR-146a (or rs3746444 in miR-499) and breast cancer susceptibility.

This meta-analysis demonstrates the compelling evidence that the rs11614913 CC genotype in miR-196a2 increases breast cancer risk, which provides useful information for the early diagnosis and prevention of breast cancer.

• Breast Neoplasms/genetics
• Case-Control Studies
• Female
• Gene Frequency
• Genetic Association Studies
• Genetic Predisposition to Disease
• Humans
• MicroRNAs/genetics
• Polymorphism, Single Nucleotide

Single nucleotide polymorphisms (SNPs) are germline variations interspersed in the human genome. These subtle changes of DNA sequence can influence the susceptibility to various pathologies including cancer. The functional meaning of SNPs is not always clear, being, the majority of them, localized in noncoding regions. The discovery of microRNAs, tiny noncoding RNAs able to bind the 3′ untranslated region (UTR) of target genes and to consequently downregulate their expression, has provided a functional explanation of how some SNPs positioned in noncoding regions contribute to cancer susceptibility. In this paper we summarize the current knowledge of the effect on cancer susceptibility of SNPs included in regions related with miRNA-dependent pathways. Hereditary cancer comes up from mutations that occur in high-penetrant predisposing tumor genes. However, a considerable part of inherited cancers arises from multiple low-penetrant predisposing gene variants that influence the behavior of cancer insurgence. Despite the established significance of such polymorphic variants in cancer predisposition, sometimes their functional role remains unknown. The discovery of a new group of genes called microRNAs (miRNAs) opened an avenue for the functional interpretation of polymorphisms involved in cancer predisposition.

• antagomir
• breast cancer
• brca1
• microrna mimic
• micrornas

• Animals
• BRCA1 Protein/genetics
• BRCA1 Protein/metabolism
• Breast Neoplasms/genetics
• Breast Neoplasms/metabolism
• Genes, BRCA1
• Humans
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Models, Biological
• Neoplasms/genetics

• Intramural NIH HHS

AIM: To investigate whether selected single nucleotide polymorphisms (SNPs) in miR-196a2, miR-27a and miR-146a genes are associated with sporadic colorectal cancer (CRC).

METHODS: In order to investigate the effect of these SNPs in CRC, we performed a case-control study of 197 cases of sporadic CRC and 212 cancer-free controls originating from the Central-European Caucasian population using TaqMan Real-Time polymerase chain reaction and allelic discrimination analysis.

RESULTS: The genotype and allele frequencies of SNPs were compared between the cases and the controls. None of the performed analysis showed any statistically significant results.

CONCLUSION: 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 study
• Colorectal cancer
• MicroRNA
• Single nucleotide polymorphism

• mirna
• mir-146a
• mir-146b-5p
• breast cancer
• rs2910164
• single nucleotide polymorphism (snp)
• mammary development
• hormone regulation
• hematopoiesis

• Animals
• Base Sequence
• Breast Neoplasms/genetics
• Breast Neoplasms/pathology
• Cell Transformation, Neoplastic/genetics
• Cell Transformation, Neoplastic/pathology
• Female
• Gene Expression Regulation, Developmental
• Gene Expression Regulation, Neoplastic
• Humans
• Mammary Glands, Human/growth & development
• Mammary Glands, Human/pathology
• Mammary Glands, Human/physiology
• MicroRNAs/genetics
• Molecular Sequence Data

• R00 CA127462 NCI NIH HHS

• Breast Neoplasms/genetics
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• MicroRNAs/genetics
• Models, Genetic
• Polymorphism, Single Nucleotide/genetics
• Publication Bias
• White People/genetics

Emerging evidence suggests that microRNAs play a critical role in the pathogenesis of breast cancer. Several molecular epidemiological studies were conducted in recent years to evaluate the association between has-miR-146a rs2910164 polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive.

We performed a meta-analysis of 6 case-control studies that included 4238 breast-cancer cases and 4469 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, this meta-analysis showed that the rs2910164 polymorphism was not associated with a significantly increased risk of breast cancer in all genetic models (for GC vs GG: OR = 1.00, 95% CI = 0.90−1.09, P_{heterpgeneity} = 0.364; for CC vs GG: OR = 1.16, 95% CI = 0.98−1.36, P_{heterpgeneity} = 0.757; for GC+CC vs GG: OR = 1.02, 95% CI = 0.93−1.12, P_{heterpgeneity} = 0.562; for CC vs GC+GG: OR = 1.10, 95% CI = 0.96−1.26, P_{heterpgeneity} = 0.441). However, in the stratified analysis by ethnicity, we found the rs2910164 polymorphism was associated with increased breast cancer risk among Europeans in homozygote comparison (CC vs. GG: OR = 1.29, 95%CI = 1.02−1.63, P_{heterpgeneity} = 0.950, P = 0.032) and recessive model (CC vs. GC+GG: OR = 1.31, 95%CI = 1.05−1.65, P_{heterpgeneity} = 0.839, P = 0.019). No publication bias was found in the present study.

This meta-analysis suggests, for the first time, that the CC homozygote of rs2910164 may contribute to breast cancer susceptibility in Europeans.

• Breast Neoplasms/genetics
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• MicroRNAs/genetics
• Models, Genetic
• Polymorphism, Single Nucleotide/genetics
• Publication Bias
• White People/genetics