Causal effects of psoriasis on breast cancer risk: The contribution of emotional distress explored by Mendelian randomization

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Psoriasis is a chronic inflammatory disease associated with an increased risk of various cancers, including breast cancer. However, the mechanisms underlying this association remain poorly understood. Negative emotional states, commonly experienced by individuals with psoriasis, may play a role in mediating this link. This study aims to investigate the causal effect of psoriasis on breast cancer risk and explore the potential mediating role of negative emotions using Mendelian randomization (MR) approaches. Genetic instruments for psoriasis and negative emotions were sourced from large-scale genome-wide association studies. Univariate MR was first performed to evaluate the direct impact of psoriasis and its subtypes on breast cancer risk. Subsequently, multivariable MR (MVMR) was used to account for the combined effects of psoriasis and negative emotions. Mediation analysis was conducted to assess the extent to which negative emotions mediate the relationship between psoriasis and breast cancer. Sensitivity analyses, including tests for heterogeneity and horizontal pleiotropy, were performed to validate the robustness of the results. The univariate MR analysis demonstrated a significant positive association between psoriasis and the risk of breast cancer [overall psoriasis: odds ratio (OR) = 1.022, 95% confidence interval (CI): 1.005-1.039, P = .013; psoriasis vulgaris: OR = 1.020, 95% CI: 1.004-1.036, P = .013; guttate psoriasis: OR = 1.017, 95% CI: 1.005-1.030, P = .006; psoriatic arthropathies: OR = 1.018, 95% CI: 1.002-1.035, P = .032; other and unspecified psoriasis: OR = 1.017, 95% CI: 1.001-1.034, P = .035]. In the multivariable MR analysis, after adjusting for negative emotions, the association between psoriasis and breast cancer became nonsignificant (overall psoriasis: OR = 1.012, 95% CI: 0.988-1.037, P = .333), indicating that negative emotions may not significantly mediate this relationship. Mediation analysis revealed that worry and anxiety feelings accounted for a significant portion of the effect of psoriasis on breast cancer risk (P = .017). These findings suggest that worry and anxiety may serve as mediators in the causal pathway linking psoriasis to an increased risk of breast cancer. This emphasizes the importance of addressing emotional health in individuals with psoriasis, which may have implications for cancer prevention strategies. Further research into the underlying biological mechanisms is warranted to better understand the clinical implications of these results.

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