Rs3746444 T>C locus in miR-499 increases the susceptibility to hepatocellular carcinoma: A meta-analysis 14812 subjects

World J Gastrointest Oncol. 2023 Jan 15;15(1):171-185. doi: 10.4251/wjgo.v15.i1.171.

Abstract

Background: Recently, many investigations have suggested that the rs3746444 T>C locus in the microRNA (miR)-499 gene may contribute to the occurrence of cancer. However, reports on the association between rs3746444 and hepatocellular carcinoma (HCC) are conflicting.

Aim: To further understand and explore the potential correlation between the single-nucleotide polymorphism of rs3746444 and the incidence of HCC.

Methods: In this meta-analysis, we obtained electronic literature by searching the PubMed, Embase and Chinese BioMedical Disc databases (through May 20, 2022). All eligible case-control, prospective cohort or nested case-control studies with sufficient data for calculating the odds ratios with their 95% confidence intervals were included.

Results: Ultimately, a total of 17 independent studies were included. We identified that rs3746444 was associated with the development of HCC (C vs T: P = 0.019 and CC/CT vs TT: P = 0.016). In Asian individuals, rs3746444 was associated with susceptibility to HCC (C vs T: P = 0.013 and CC/CT vs TT: P = 0.016). In addition, this study identified that the miR-499 rs3746444 locus was associated with susceptibility to HCC in the normal/healthy control subgroup (C vs T: P = 0.034 and CC/CT vs TT: P = 0.024).

Conclusion: In summary, this meta-analysis highlights that rs3746444 in the miR-499 gene is involved in the occurrence of HCC, especially in Asian individuals.

Keywords: Hepatocellular carcinoma; Meta-analysis; MicroRNA-499; Polymorphism; Susceptibility.