Association of a genetic variant in Interleukin-10 gene with increased risk and inflammation associated with cervical cancer

Gene. 2022 Jan 10:807:145933. doi: 10.1016/j.gene.2021.145933. Epub 2021 Aug 28.

Abstract

Background: Cervical-cancer is among the most commonly diagnosed cancers in women, and infection with human papillomavirus (HPV) is associated with an increased risk of cervical cancer and altered serum concentrations of inflammatory cytokines. We have explored the association between a genetic variation in the Interleukin-10 (IL-10) gene (rs1800896) and cervical cancer risk and its relationship with tissue Interferon gamma (IFN-γ), Transforming growth factor beta (TGF-β), Tumor necrosis factor alpha (TNF-α) concentrations in women with cervical cancer.

Methods: A total of 315 women with, or without cervical cancer, were recruited into the study. DNA was extracted from cervical cells, and genotyping was undertaken using Taq-man real-time PCR. The genotype frequency and allele distribution were analyzed together with their association with pathological data. The association of the rs1800896 gene variation with tissue levels of the inflammatory cytokines was also investigated.

Results: Our data showed a significant association between the A allele of the rs1800896 gene variant and the presence of cervical cancer. In particular, patients with AG/AA genotypes had an increased risk of cervical cancer with an odds ratio of 1.929 (95% confidence interval [CI]: 0.879-4.23, P < 0.001) in a recessive model, compared with the GG genotype. Also, the tissue concentrations of IFN-γ, TGF-β, and TNF-α in cervical tissues were significantly higher in women with cervical cancer (P < 0.001) and were associated with the AA genotype.

Conclusion: We have found an association between the polymorphism rs1800896 in the IL-10 gene and an increased risk of cervical cancer as well as a higher level of tissue inflammatory cytokines. Further investigations are necessary on the value of emerging biomarkers for the risk stratification for the management of cervical cancer patients.

Keywords: Cervical cancer; Human papillomavirus; IFN-γ; Interleukin 10; TGF-β; TNF-α.

MeSH terms

  • Adult
  • Alleles
  • Alphapapillomavirus / genetics
  • Alphapapillomavirus / pathogenicity
  • Cytokines
  • Female
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Inflammation
  • Interferon-gamma
  • Interleukin-10 / genetics*
  • Interleukin-10 / metabolism
  • Middle Aged
  • Odds Ratio
  • Papillomaviridae / genetics
  • Papillomaviridae / pathogenicity
  • Polymorphism, Single Nucleotide / genetics
  • Real-Time Polymerase Chain Reaction
  • Risk Factors
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Uterine Cervical Neoplasms / genetics*

Substances

  • Cytokines
  • IL10 protein, human
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma