Two-sample Mendelian Randomization to evaluate the causal relationship between inflammatory arthritis and female-specific cancers

Abstract

Abstract Background There is evidence that inflammatory arthritis in the form of ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis are both positively and negatively associated with certain female-specific cancers. However, the study results are very heterogeneous. Methods Based on up to 375,814 European women, we performed an iterative two-sample Mendelian randomization to assess causal effects of the occurrence of the inflammatory arthritis on the risk of female-specific cancer in form of breast, endometrial, and ovarian cancer sites as well as their subtypes. Evidence was strengthened by using similar exposures for plausibility or by replication with a subsequent meta-analysis. P-values were Bonferroni adjusted. Results Genetic liability to AS was associated with ovarian cancer (OR = 1.03; 95% CI: [1.01; 1.04]; $$\:{P}_{adj}$$ =0.029) and liability to PsA with breast cancer (OR = 1.02; CI: [1.01; 1.04]; $$\:{P}_{adj}$$ =0.002). Subgroup analyses revealed that the high-grade serous ovarian cancer (OR = 1.04; CI: [1.02; 1.06]; $$\:{P}_{adj}$$ =0.015) and the ER- breast cancer (OR = 1.04; CI: [1.01; 1.07]; $$\:{P}_{adj}$$ =0.118) appeared to drive the observed associations, respectively. No further associations were found between the remaining inflammatory arthritis phenotypes and female-specific cancers. Conclusions This study suggests that AS is a risk factor for ovarian cancer, while PsA is linked to an increased breast cancer risk. These results are important for physicians caring women with inflammatory arthritis to advise their patients on cancer screening and preventive measures.

Keywords

• Mendelian randomization
• Ovarian cancer
• Breast cancer
• Autoimmune disease
• Ankylosing spondylitis
• Psoriatic arthritis