Autoimmune diseases and female-specific cancer risk: A systematic review and meta-analysis.

Simone Fischer, Christa Meisinger, Dennis Freuer

Journal: Journal of autoimmunity 2024;144():103187

PMID: 38428110

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Plain Language Summary

Autoimmune diseases are characterised by chronic inflammation, and having an autoimmune condition increases the risk of developing some cancers. Previous studies have shown an association between psoriasis, rheumatoid arthritis, and ankylosing spondylitis and an increased or decreased risk of developing specific cancers. Due to the hormonal changes that affect the immune system in women during their lifetime, women are generally susceptible to developing autoimmune diseases. This systematic review and meta-analysis investigated the presence of autoimmune conditions such as psoriasis, rheumatoid arthritis and ankylosing spondylitis in women and how it increases the risk of developing female site-specific cancers such as breast, ovarian, uterine, cervical, vulvar and vaginal cancers. The results of this study indicated that there is a negative relationship between rheumatoid arthritis and breast and uterine cancers. It was also found that psoriasis can elevate the risk of developing breast cancer. Additionally, a subgroup analysis demonstrated a connection between geographical location and the risk of developing specific cancers in women with rheumatoid arthritis. The differences in cancer susceptibility in various geographical locations may be due to lifestyle factors, environmental influences, and genetic predisposition. Healthcare professionals can use the evidence from this study to understand the impact of female hormones on the regulation of inflammation and immunity. The study also highlights how changes in hormone levels can increase the risk of female-specific cancers. Further robust studies are needed to investigate the potential therapeutic effects and mechanisms underlying the increased risk of cancers associated with female hormones.

Abstract

OBJECTIVES

Among the over 80 different autoimmune diseases, psoriasis (PsO), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) are common representatives. Previous studies indicated a potential link with cancer risk, but suffered often from low statistical power. Thus, we aimed to synthesize the evidence and quantify the association to different female-specific cancer sites.

METHODS

The systematic review was performed according to PRISMA guidelines. A search string was developed for the databases PubMed, Web of Science, Cochrane Library and Embase. Results were screened independently by two investigators and the risk of bias was assessed using the ROBINS-E tool. Meta-analyses were performed using inverse variance weighted random-effects models. Statistical between-study heterogeneity was quantified by calculating Cochran's Q, τ, and Higgins' I statistics. Sources of heterogeneity were analyzed and adjusted for within an intensive bias assessment in the form of meta-regression, outlier, influential, and subgroup analyses. A range of methods were used to test and adjust for publication bias.

RESULTS

Of 10,096 records that were originally identified by the search strategy, 45 were included in the meta-analyses. RA was inversely associated with both breast and uterine cancer occurrence, while PsO was associated with a higher breast cancer risk. Outlier-adjusted estimates confirmed these findings. Bias assessment revealed differences in geographic regions, particularly in RA patients, with higher estimates among Asian studies. An additional analysis revealed no association between psoriatic arthritis and breast cancer.

CONCLUSIONS

RA seems to reduce the risk of breast and uterine cancers, while PsO appears to increase breast cancer risk. Further large studies are required to investigate potential therapy-effects and detailed biological mechanisms.

Address: Epidemiology, Medical Faculty, University of Augsburg, Augsburg, Germany. Electronic address: [email protected].; Epidemiology, Medical Faculty, University of Augsburg, Augsburg, Germany.

DOI: 10.1016/j.jaut.2024.103187