The association between three prevalent autoimmune disorders and the likelihood of developing prostate cancer: a Mendelian randomization study

Abstract

Numerous studies establish a significant correlation between autoimmune disorders (AIDs) and prostate cancer (PCa). Our Mendelian randomization (MR) analysis investigates the potential connection between rheumatoid arthritis (RA) and PCa, aiming to confirm causal links between systemic lupus erythematosus (SLE), hyperthyroidism, and PCa. Summary statistics from genome-wide association studies provided data on PCa and three AIDs. MR analysis, using IVW as the main approach, assessed causal relationships, validated by sensitivity analysis. IVW revealed a correlation between genetically anticipated RA and PCa, notably in Europeans (OR = 1.03; 95% CI 1.01-1.04, p = 2*10-5). Evidence supported a lower PCa risk in individuals with SLE (OR = 0.94; 95% CI 0.91-0.97, p = 2*10-4) and hyperthyroidism (OR = 0.02; 95% CI 0.001-0.2, p = 2*10-3). Weighted mode and median confirmed these findings. No pleiotropic effects were observed, and MR heterogeneity tests indicated dataset homogeneity. Our study establishes a causal link between RA, SLE, hyperthyroidism, and PCa.

Keywords: Autoimmune disorders; Cancer risk; Genome-wide association study; Hyperthyroidism; Mendelian randomization; Prostate cancer; Rheumatoid arthritis; Systemic lupus erythematosus.

Figure 1

SNPs used as IVs in the two-sample MR analysis. (Single nucleotide polymorphisms (SNPs) used as IVs in the two-sample MR analysis ought to adhere to the following three fundamental presumptions: (1) IVs are strongly correlated with exposure; (2) IVs are unrelated to any confounding variables; and (3) IVs only have an impact on the outcome through exposure. The MR framework's directed graph looks into the connection between RA and AIDs).

Figure 2

The funnel plot of the causal effect of AIDs SNPs on PCa. (The MR-Egger and IVW were used for the analyses. Individual SNP was delineated in the background. A RA; B SLE; C Hyperthyroidism).

Figure 3

The leave-one-out plot of the causal effect of AIDs SNPs on PCa. (A RA; B SLE; C Hyperthyroidism).

Figure 4

The forest plot of the causal effect of AIDs SNPs on PCa. (A RA; B SLE; C Hyperthyroidism).

Figure 5

The scatter plot of the causal effect of AIDs SNPs on PCa. The weighted median, MR-Egger, IVW, weighted mode methods and simple mode were used for the analyses. The slope of each line represents the causal estimates for each method. (A RA; B SLE; C Hyperthyroidism) SNP, single nucleotide polymorphism; MR, Mendelian.