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. 2024 Oct 24;22(1):962.
doi: 10.1186/s12967-024-05765-9.

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

Christa Meisinger  1 , Simone Fischer  2 , Tracy O'Mara  3 , Dennis Freuer  2
Affiliations

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

Christa Meisinger et al. J Transl Med. .

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]; [Formula: see text]=0.029) and liability to PsA with breast cancer (OR = 1.02; CI: [1.01; 1.04]; [Formula: see text]=0.002). Subgroup analyses revealed that the high-grade serous ovarian cancer (OR = 1.04; CI: [1.02; 1.06]; [Formula: see text]=0.015) and the ER- breast cancer (OR = 1.04; CI: [1.01; 1.07]; [Formula: see text]=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: Ankylosing spondylitis; Autoimmune disease; Breast cancer; Mendelian randomization; Ovarian cancer; Psoriatic arthritis; Rheumatoid arthritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Estimates for the causal effects of ankylosing spondylitis (using the usual and a strict definition) on female-specific cancers given as odds ratios (ORs) and 95% confidence intervals. Presented P-values are Bonferroni-adjusted. A gray background represents the main and the unshaded background the subgroup analyses of the respective cancer site
Fig. 2
Fig. 2
Estimates for the causal effects of psoriasis and psoriatic arthritis on female-specific cancers given as odds ratios (ORs) and 95% confidence intervals. Presented P-values are Bonferroni-adjusted. A gray background represents the main and the unshaded background the subgroup analyses of the respective cancer site
Fig. 3
Fig. 3
Estimates for the causal effects of rheumatoid arthritis on female-specific cancers, consisting of two individual studies and a pooled estimate from a fixed-effect meta-analysis. Results are presented as odds ratios (ORs), 95% confidence intervals, and Bonferroni-adjusted P-values. A gray background represents the main and the unshaded background the subgroup analyses of the respective cancer site
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