Association between three functional microRNA polymorphisms (miR-499 rs3746444, miR-196a rs11614913 and miR-146a rs2910164) and breast cancer risk: a meta-analysis

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.

[1]  Sebastian Morales,et al.  Association of single nucleotide polymorphisms in Pre-miR-27a, Pre-miR-196a2, Pre-miR-423, miR-608 and Pre-miR-618 with breast cancer susceptibility in a South American population , 2016, BMC Genetics.

[2]  Amir Mehrgou,et al.  The importance of BRCA1 and BRCA2 genes mutations in breast cancer development , 2016, Medical journal of the Islamic Republic of Iran.

[3]  Z. Dai,et al.  The Associations of Single Nucleotide Polymorphisms in miR196a2, miR-499, and miR-608 With Breast Cancer Susceptibility , 2016, Medicine.

[4]  S. Chambers,et al.  Association of the microRNA-Single Nucleotide Polymorphism rs2910164 in miR146a with sporadic breast cancer susceptibility: A case control study. , 2016, Gene.

[5]  Christopher I. Jones,et al.  Mechanisms of regulation of mature miRNAs. , 2015, Biochemical Society transactions.

[6]  Peng Chen,et al.  Pri-Mir-34b/C and Tp-53 Polymorphisms are Associated With The Susceptibility of Papillary Thyroid Carcinoma , 2015, Medicine.

[7]  Bing-he Xu,et al.  [Polymorphisms of microRNA genes and their association with breast cancer risk]. , 2015, Zhonghua zhong liu za zhi [Chinese journal of oncology].

[8]  L. Wang,et al.  Associations of miRNA polymorphisms and expression levels with breast cancer risk in the Chinese population. , 2015, Genetics and molecular research : GMR.

[9]  Michael J. Kerin,et al.  Effects of Age on the Detection and Management of Breast Cancer , 2015, Cancers.

[10]  F. Ren,et al.  Association of miR-146a rs2910164 polymorphism with squamous cell carcinoma risk: a meta-analysis. , 2015, Journal of B.U.ON. : official journal of the Balkan Union of Oncology.

[11]  Hong-zhao Li,et al.  MicroRNA-185 inhibits cell proliferation and induces cell apoptosis by targeting VEGFA directly in von Hippel-Lindau-inactivated clear cell renal cell carcinoma. , 2015, Urologic oncology.

[12]  Z. Dai,et al.  Five common functional polymorphisms in microRNAs (rs2910164, rs2292832, rs11614913, rs3746444, rs895819) and the susceptibility to breast cancer: evidence from 8361 cancer cases and 8504 controls. , 2015, Current pharmaceutical design.

[13]  A. Jemal,et al.  Global cancer statistics, 2012 , 2015, CA: a cancer journal for clinicians.

[14]  Yu-qin Pan,et al.  Associations of polymorphisms in microRNAs with female breast cancer risk in Chinese population , 2015, Tumor Biology.

[15]  S. Zhong,et al.  Lack of association between Hsa-Mir-499 rs3746444 polymorphism and cancer risk: meta-analysis findings. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[16]  Shan Li,et al.  The Association of Common Functional Polymorphisms in Mir-146a and Mir-196a2 and Hepatocellular Carcinoma Risk , 2014, Medicine.

[17]  Xiao-fan Wang,et al.  MiR-146a rs2910164 polymorphism increases risk of gastric cancer: a meta-analysis. , 2014, World journal of gastroenterology.

[18]  B. Mittal,et al.  Common genetic variants in pre-microRNAs and risk of breast cancer in the North Indian population , 2014, Ecancermedicalscience.

[19]  L. Tian,et al.  MicroRNA-195 inhibits non-small cell lung cancer cell proliferation, migration and invasion by targeting MYB. , 2014, Cancer letters.

[20]  M. Taheri,et al.  hsa-mir-499 rs3746444 gene polymorphism is associated with susceptibility to breast cancer in an Iranian population. , 2014, Biomarkers in medicine.

[21]  M. Manikandan,et al.  Single nucleotide polymorphisms in microRNA binding sites of oncogenes: implications in cancer and pharmacogenomics. , 2014, Omics : a journal of integrative biology.

[22]  X. Chen,et al.  A genetic variant in pre-miR-27a is associated with a reduced breast cancer risk in younger Chinese population. , 2013, Gene.

[23]  Q. Cui,et al.  MiR-499 Regulates Cell Proliferation and Apoptosis during Late-Stage Cardiac Differentiation via Sox6 and Cyclin D1 , 2013, PloS one.

[24]  S. Xie,et al.  The Associations of Single Nucleotide Polymorphisms in miR-146a, miR-196a and miR-499 with Breast Cancer Susceptibility , 2013, PloS one.

[25]  D. Lin,et al.  There Is No Association between MicroRNA Gene Polymorphisms and Risk of Triple Negative Breast Cancer in a Chinese Han Population , 2013, PloS one.

[26]  Qing-Bing Wang,et al.  Ethnicity modifies the association between functional microRNA polymorphisms and breast cancer risk: a HuGE meta-analysis , 2013, Tumor Biology.

[27]  T. Bonetti,et al.  Evaluation of single nucleotide polymorphisms in microRNAs (hsa-miR-196a2 rs11614913 C/T) from Brazilian women with breast cancer , 2012, BMC Medical Genetics.

[28]  Yang Wang,et al.  Hsa-miR-499 polymorphism (rs3746444) and cancer risk: a meta-analysis of 17 case-control studies. , 2012, Gene.

[29]  G. Sun,et al.  Association of microRNA-499 rs3746444 Polymorphism with Cancer Risk: Evidence from 7188 Cases and 8548 Controls , 2012, PloS one.

[30]  S. Maheswaran,et al.  HOXB9 Expression Promoting Tumor Cell Proliferation and Angiogenesis Is Associated with Clinical Outcomes in Breast Cancer Patients , 2012, Annals of Surgical Oncology.

[31]  H. Liu,et al.  Associations of miRNA polymorphisms and female physiological characteristics with breast cancer risk in Chinese population. , 2012, European journal of cancer care.

[32]  A. Alshatwi,et al.  Differential Expression Profile and Genetic Variants of MicroRNAs Sequences in Breast Cancer Patients , 2012, PloS one.

[33]  Robert A. Smith,et al.  Single Nucleotide Polymorphism in hsa-mir-196a-2 and Breast Cancer Risk: A Case Control Study , 2011, Twin Research and Human Genetics.

[34]  A. Antoniou,et al.  The rs2910164:G>C SNP in the MIR146A gene is not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers , 2011, Human mutation.

[35]  Ke-Xin Chen,et al.  Chinese Anti鄄 Cancer a Ssociation , 2022 .

[36]  Chiara Pastrello,et al.  Association between hsa-mir-146a genotype and tumor age-of-onset in BRCA1/BRCA2-negative familial breast and ovarian cancer patients. , 2010, Carcinogenesis.

[37]  C. Harris,et al.  Genetic variation in microRNA networks: the implications for cancer research , 2010, Nature Reviews Cancer.

[38]  P. Bugert,et al.  Evaluation of SNPs in miR‐146a, miR196a2 and miR‐499 as low‐penetrance alleles in German and Italian familial breast cancer cases , 2010, Human mutation.

[39]  P. Donahoe,et al.  HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis , 2009, Proceedings of the National Academy of Sciences.

[40]  F. Slack,et al.  microRNA miR-196a-2 and breast cancer: a genetic and epigenetic association study and functional analysis. , 2009, Cancer research.

[41]  Hongbing Shen,et al.  Common genetic variants in pre‐microRNAs were associated with increased risk of breast cancer in Chinese women , 2009, Human mutation.

[42]  D. Bartel,et al.  MicroRNA-Directed Cleavage of HOXB8 mRNA , 2004, Science.

[43]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.