# Genetic association of miR-146a, miR-196a2, and miR-499 polymorphisms with hepatocellular carcinoma risk in an Eastern Chinese population

**Authors:** Lunjun Zhang, Qing Pang, Hongtao Wang, Tao Xu, Xiaolin Ding

PMC · DOI: 10.3389/fonc.2026.1707963 · Frontiers in Oncology · 2026-02-06

## TL;DR

This study finds that certain genetic variations in miR-196a2 and miR-499 are linked to increased or decreased risk of liver cancer in an Eastern Chinese population.

## Contribution

The study identifies novel associations between miR-196a2 and miR-499 polymorphisms and hepatocellular carcinoma risk in an Eastern Chinese population.

## Key findings

- miR-196a2 rs11614913 CT/TT genotypes increase HCC risk in Eastern Chinese individuals.
- miR-499 rs3746444 AG/GG genotypes are linked to reduced HCC risk.
- miR-146a rs2910164 shows no significant association with HCC risk.

## Abstract

Hepatocellular carcinoma (HCC) ranks as the sixth most common cancer and the third leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) are known to regulate oncogenic and tumor suppressor pathways, and single nucleotide polymorphisms (SNPs) in miRNAs may influence cancer susceptibility.

We investigated the association between three miRNA SNPs—miR-146a rs2910164, miR-196a2 rs11614913, and miR-499 rs3746444—and the risk of HCC in an eastern Chinese population. A total of 353 HCC patients and 351 healthy controls were enrolled. Genotyping was performed using PCR-ligase detection reaction (PCR-LDR), and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.

Compared with the CC genotype, individuals carrying the CT and TT genotypes of miR-196a2 rs11614913 exhibited significantly increased risks of HCC (OR = 1.61, 95% CI: 1.10-2.37; OR: 1.66, 95% CI: 1.07-2.55). The dominant model of miR-196a2 rs11614913 also showed a significant association with HCC risk (P = 0.009). In contrast, carriers of the AG or GG genotype of miR-499 rs3746444 showed a reduced HCC risk (OR = 0.72, 95% CI: 0.52–0.99, P = 0.048). No significant association was found for miR-146a rs2910164 and HCC risk.

Our findings suggest that miR-196a2 rs11614913 and miR-499 rs3746444 polymorphisms are significantly associated with HCC susceptibility in the eastern Chinese population and may serve as potential genetic biomarkers for early risk assessment.

## Linked entities

- **Genes:** MIR146A (microRNA 146a) [NCBI Gene 406938], MIR196A2 (microRNA 196a-2) [NCBI Gene 406973], MIR499A (microRNA 499a) [NCBI Gene 574501]
- **Diseases:** hepatocellular carcinoma (MONDO:0007256)

## Full-text entities

- **Genes:** REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, HMGA2 (high mobility group AT-hook 2) [NCBI Gene 8091] {aka BABL, HMGI-C, HMGIC, LIPO, SRS5, STQTL9}, ANXA1 (annexin A1) [NCBI Gene 301] {aka ANX1, LPC1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, PDCD4 (programmed cell death 4) [NCBI Gene 27250] {aka H731}, MIR192 (microRNA 192) [NCBI Gene 406967] {aka MIRN192, miR-192, miRNA192}, MIR449B (microRNA 449b) [NCBI Gene 693123] {aka MIRN449B, mir-449b}, MIR146A (microRNA 146a) [NCBI Gene 406938] {aka MIRN146, MIRN146A, miR-146a, miRNA146A}, HOXC@ (homeobox C cluster) [NCBI Gene 3220] {aka HOX3@}, HOXB@ (homeobox B cluster) [NCBI Gene 3210] {aka HOX2@}, TRAF6 (TNF receptor associated factor 6) [NCBI Gene 7189] {aka MGC:3310, RNF85}, MIR499A (microRNA 499a) [NCBI Gene 574501] {aka MIR499, MIRN499, hsa-mir-499a, mir-499a}, IRAK1 (interleukin 1 receptor associated kinase 1) [NCBI Gene 3654] {aka IRAK, pelle}, SULT1E1 (sulfotransferase family 1E member 1) [NCBI Gene 6783] {aka EST, EST-1, ST1E1, STE}, MIR196A2 (microRNA 196a-2) [NCBI Gene 406973] {aka MIRN196-2, MIRN196A2, mir-196a-2}, SOX6 (SRY-box transcription factor 6) [NCBI Gene 55553] {aka HSSOX6, SOXD, TOLCAS}
- **Diseases:** metabolic disorders (MESH:D008659), oncogenes (MESH:D000074723), carcinogenesis (MESH:D063646), liver cirrhosis (MESH:D008103), esophageal squamous cell carcinoma (MESH:D000077277), HBV infection (MESH:D006509), Cancer (MESH:D009369), hepatic inflammatory (MESH:D007249), cirrhosis (MESH:D005355), HCC (MESH:D006528), breast cancer (MESH:D001943), digestive system diseases (MESH:D004066), end-stage liver or kidney disease (MESH:D007676), endocrine disorders (MESH:D004700), chronic viral hepatitis (MESH:D006525), deaths (MESH:D003643), metastasis (MESH:D009362)
- **Chemicals:** sorafenib (MESH:D000077157), aflatoxin (MESH:D000348), aldosterone (MESH:D000450), alcohol (MESH:D000438)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** rs10061133, rs2910164, T>C, C to T, rs2292832, rs12220909, rs11614913, G to C
- **Cell lines:** HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027)

## Full text

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## Figures

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## References

55 references — full list in the complete paper: https://tomesphere.com/paper/PMC12920222/full.md

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Source: https://tomesphere.com/paper/PMC12920222