Association between MIR499A rs3746444 polymorphism and breast cancer susceptibility: a meta-analysis

Shing Cheng Tan,Mira Farzana Mohamad Mokhtar,Ezanee Azlina Mohamad Hanif,Rahman Jamal,Poh Ying Lim,Jie Fang

doi:10.1038/s41598-020-60442-3

Shing Cheng Tan, Mira Farzana Mohamad Mokhtar + Show 4 more

Open Access

https://doi.org/10.1038/s41598-020-60442-3

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Abstract

Numerous studies have investigated the association of MIR499A rs3746444 polymorphism with breast cancer susceptibility, but the results have been inconsistent. In this work, we performed a meta-analysis to obtain a more reliable estimate of the association between the polymorphism and susceptibility to breast cancer. A comprehensive literature search was conducted on PubMed, Scopus, Web of Science (WoS), China National Knowledge Infrastructure (CNKI), VIP and Wanfang databases up to January 2020. A total of 14 studies involving 6,797 cases and 8,534 controls were included for analysis under five genetic models: homozygous (GG vs. AA), heterozygous (AG vs. AA), dominant (AG + GG vs. AA), recessive (GG vs. AA + AG) and allele (G vs. A). A statistically significant association was observed between the polymorphism and an increased breast cancer susceptibility under all genetic models (homozygous, OR = 1.33, 95% CI = 1.03–1.71, P = 0.03; heterozygous, OR = 1.08, 95% CI = 1.00–1.16, P = 0.04; dominant, OR = 1.15, 95% CI = 1.02–1.30; P = 0.03; recessive, OR = 1.35, 95% CI = 1.06–1.72, P = 0.01; allele, OR = 1.12, 95% CI = 1.00–1.26, P = 0.04). Subgroup analysis based on ethnicity suggested that significant association was present only among Asians, but not Caucasians. In conclusion, MIR499A rs3746444 polymorphism was significantly associated with breast cancer susceptibility among Asians, suggesting its potential use as a genetic risk marker in this population.

Highlights

Breast cancer is the most common type of cancer and the leading contributor to cancer-related deaths in women worldwide[1]
Eligible studies were selected based on the following criteria: (i) those that investigated the association between MIR499A rs3746444 polymorphism and breast cancer susceptibility; (ii) case-control or cohort in design; and (iii) contained data on genotype and allele frequencies or sufficient data to derive this information
MicroRNAs are an emerging class of post-transcriptional regulators which have been implicated in oncogenesis

Summary

Introduction

Breast cancer is the most common type of cancer and the leading contributor to cancer-related deaths in women worldwide[1]. In contrast to high penetrance mutations, genetic polymorphisms are very common in the general population, but are typically associated with a modest risk of cancer. In non-small cell lung cancer, miR-499a was found to exert its tumor suppressive function by targeting VAV3 oncogene[13]. Polymorphisms occurring in the seed region of a microRNA gene may contribute to its oncogenic or tumor suppressive functions and subsequently affect cancer risk or susceptibility. One such polymorphism is rs3746444, which results from an A-to-G substitution in the seed region of MIR499A. A number of studies have examined the association of the polymorphism with breast cancer susceptibility, but the results obtained have been inconsistent. In this work, we aimed to pool the study findings via a meta-analysis in order to derive a more precise estimate of the association between MIR499A rs3746444 polymorphism and breast cancer susceptibility

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