Exploring the causal association between rheumatoid arthritis and the risk of cervical cancer: a two-sample Mendelian randomization study

Arthritis Res Ther. 2024 Jan 23;26(1):35. doi: 10.1186/s13075-023-03240-2.

Abstract

Objective: Whether rheumatoid arthritis patients have an increased risk of cervical cancer remains controversial, and further research is needed on this clinical question. This study aims to investigate the association between rheumatoid arthritis and the susceptibility to cervical cancer by employing Mendelian randomization methodology, utilizing the extensive dataset from human genome-wide association data analysis.

Methods: The publicly accessible MR base database was utilized to obtain the complete genome, relevant research findings, and summarized data pertaining to rheumatoid arthritis and cervical cancer. Genetic tool variables, specifically single-nucleotide polymorphisms closely linked to rheumatoid arthritis, were chosen for analysis. Four methods, namely inverse variance weighted analysis, weighted median analysis, weighted mode, and MR-Egger regression, were employed. Statistical analysis was conducted to explore the potential association between rheumatoid arthritis and susceptibility to cervical cancer.

Results: The results of the inverse variance weighted analysis (OR = 1.096, 95% CI: 1.018-1.180, P = 0.015) indicate a significant causal relationship between rheumatoid arthritis and an increased risk of cervical cancer. Furthermore, the absence of horizontal pleiotropic effects (MR-Egger intercept = 0.00025, P = 0.574) and heterogeneity (QEgger = 2.239, I2Egger = 0.225, PEgger = 0.268, QIVW = 2.734, I2IVW = 0.220, PIVW = 0.999) suggests that the observed association is not influenced by confounding factors. Sensitivity analysis and other statistical methods also support the conclusion that genetic pleiotropy does not introduce bias to the findings.

Conclusion: There is a causal relationship between rheumatoid arthritis and the occurrence of cervical cancer. People with rheumatoid arthritis is one of the high-risk groups for early screening of cervical cancer. The IL-18 may play a significant role in elevating the risk of cervical cancer among rheumatoid arthritis patients.

Keywords: Causal relationship; Cervical cancer; Mendelian randomization; Rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid*
  • Databases, Factual
  • Female
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Uterine Cervical Neoplasms*