Genetic variants in microRNAs are associated with cervical cancer risk

Mutagenesis. 2019 May 29;34(2):127-133. doi: 10.1093/mutage/gez005.

Abstract

Because genetic variants in microRNAs (miRNAs) or their surrounding regions can alter miRNA processing, expression and final biological function, we investigated whether miRNA single-nucleotide polymorphisms (SNPs) are associated with cervical cancer (CC) susceptibility. Common miRNA SNPs (i.e. miR-146a rs2910164, miR-149 rs2292832, miR-196a2 rs11614913, miR-499 rs3746444, miR-605 rs2043556 and miR-618 rs2682818) were genotyped in the 954 patients and 1339 controls. The results showed that the miR-149 rs2292832 TC/CC genotypes were associated with a 21% increased risk of CC compared with the TT genotype [odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.00-1.47]. The association was more prominent among the subjects with age ≤ 48 years (OR = 1.55, 95% CI = 1.16-2.06), having history of abortion (OR = 1.44, 95% CI = 1.12-1.86), premenopausal status (OR = 1.41, 95% CI = 1.08-1.85) and patients with clinical stage II of CC (OR = 1.43, 95% CI = 1.08-1.90). The expression plasmids containing the pre-miR-149 sequence with C allele of rs2292832 transcribed higher amount of mature miR-149-5p/3p than these with T allele in the HeLa and SiHa cells. Therefore, the rs2292832 polymorphism might influence CC susceptibility through modulation of the procession of pre-miR-149 to mature miRNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Alleles
  • Asian People / genetics
  • Carcinoma, Adenosquamous / genetics
  • Carcinoma, Adenosquamous / metabolism
  • Carcinoma, Adenosquamous / pathology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Genetic Predisposition to Disease
  • HeLa Cells
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • MIRN149 microRNA, human
  • MicroRNAs