Systemic lupus erythematosus and prostate cancer risk: a pool of cohort studies and Mendelian randomization analysis

Abstract

Background: Current observational studies suggest that there may be a causal relationship between systemic lupus erythematosus (SLE) and prostate cancer (PC). However, there is contradictory evidence. This study aimed to investigate and clarify the association between SLE and PC. Methods: We searched PubMed, Embase, Web of Science, and Scopus until May 2022. A meta-analysis was conducted on the standard incidence rate (SIR) and 95% CI. Subgroup analysis was performed based on the follow-up duration, study quality, and appropriate SLE diagnosis. Mendelian randomization (MR) of the two samples was used to determine whether genetically elevated SLE was causal for PC. Summary MR data were obtained from published GWASs, which included 1,959,032 individuals. The results were subjected to sensitivity analysis to verify their reliability. Results: In a meta-analysis of 79,316 participants from 14 trials, we discovered that patients with SLE had decreased PC risk (SIR, 0.78; 95% CI, 0.70–0.87) significantly. The MR results showed that a one-SD increase in genetic susceptibility to SLE significantly reduced PC risk (OR, 0.9829; 95% CI, 0.9715–0.9943; P = 0.003). Additional MR analyses suggested that the use of immunosuppressants (ISs) (OR, 1.1073; 95% CI, 1.0538–1.1634; P < 0.001), but not glucocorticoids (GCs) or non-steroidal anti-inflammatory drugs (NSAIDs), which were associated with increased PC risk. The results of the sensitivity analyses were stable, and there was no evidence of directional pleiotropy. Conclusions: Our results suggest that patients with SLE have a lower risk of developing PC. Additional MR analyses indicated that genetic susceptibility to the use of ISs, but not GCs or NSAIDs, was associated with increased PC risk. This finding enriches our understanding of the potential risk factors for PC in patients with SLE. Further study is required to reach more definitive conclusions regarding these mechanisms.