In a groundbreaking genetic investigation published in BMC Cancer, researchers have unveiled nuanced relationships between psoriasis and the risk profiles of 33 common cancers. Utilizing the robust Mendelian randomization (MR) approach, this extensive study sheds light on how the genetic architecture of psoriasis may influence cancer susceptibility, revealing potential protective effects against certain malignancies. This insight emerges at a time when the scientific community intensifies its quest to disentangle the complex interplay between chronic inflammatory diseases and cancer development.
Psoriasis, a chronic autoimmune disorder characterized by persistent skin inflammation, has long been observed in epidemiological studies to correlate with increased risks of various cancers. However, these observational associations often suffer from confounding factors and reverse causation, leaving unresolved questions about causality. To address these limitations, Liu and colleagues harnessed the power of Mendelian randomization, a method leveraging naturally occurring genetic variants as instrumental variables to infer causal relationships between risk factors and disease outcomes.
The researchers began by selecting 49 independent single-nucleotide polymorphisms (SNPs) robustly associated with psoriasis from a large-scale genome-wide association study (GWAS) meta-analysis. These genetic markers served as proxies for lifetime psoriasis exposure, minimizing confounding and bias inherent in observational analyses. Outcome data on cancer incidence were extracted from extensive GWAS datasets, including the FinnGen consortium with over 500,000 participants, the UK Biobank encompassing more than 420,000 individuals, and multiple other large-scale cancer cohorts.
Employing the inverse-variance weighted (IVW) statistical method as the primary analytical tool, the team meticulously examined the relationship between psoriasis genetic liability and cancer risk. Meta-analytic techniques were subsequently applied to integrate findings across different populations, enhancing the statistical power and reliability of the results. This comprehensive approach allowed for a detailed interrogation of 33 cancer types, ranging from solid tumors to hematologic malignancies.
Intriguingly, the analysis revealed that genetically predicted psoriasis exhibited a suggestive, albeit modest, protective association with uterine corpus cancer and prostate cancer. Specifically, in the UK Biobank data, psoriasis-related genetic variants corresponded to a slight decrease in uterine corpus cancer risk, with an odds ratio (OR) just below unity, indicating reduced likelihood. A similar inverse genetic association for prostate cancer emerged from both the FinnGen consortium and an independent large cancer dataset, reinforcing the potential protective narrative.
Conversely, certain cancers such as colon and vulvar cancer displayed inconsistent directional associations across diverse datasets, complicating interpretative clarity. While UK Biobank data suggested psoriasis might elevate colon cancer risk, Finnish genetic data hinted at an increased risk for vulvar cancer. However, these findings did not withstand meta-analytical consolidation, underscoring the heterogeneity and potential population-specific influences governing these cancer risks.
Notably, none of the other 29 examined cancer types displayed statistically significant associations with psoriasis genetic liability, suggesting a highly specific pattern of interaction rather than a broad oncogenic or protective effect. This specificity underscores the importance of dissecting genetic determinants within distinct biological contexts rather than extrapolating generalized cancer risk from systemic inflammatory states alone.
Mechanistically, these observations challenge prevailing assumptions about chronic inflammation universally predisposing individuals to elevated cancer risk. Instead, the findings imply that certain immunogenetic pathways active in psoriasis may confer protective immunosurveillance or other beneficial effects against tumorigenesis in hormonally influenced cancers like those of the uterus and prostate. Future functional studies are warranted to elucidate the molecular underpinnings linking psoriasis genetics to modulation of cancer biology.
This pioneering MR study exemplifies the growing utility of genetic epidemiology in redefining disease interrelations, moving beyond correlative observations toward causally informative insights. By leveraging large biobank data and cutting-edge statistical genetics methods, the research exemplifies precision medicine’s promise to tailor risk predictions and illuminate unexpected disease connections.
From a clinical perspective, these findings invite reconsideration of psoriasis patients’ cancer screening and prevention strategies, particularly concerning reproductive and prostate cancers. While the protective associations are subtle, awareness of this relationship may influence surveillance guidelines and personalize management. Moreover, understanding the immunological crossroads of psoriasis and cancer may inspire novel therapeutic targets that harness protective immune mechanisms.
However, interpretations should be cautious, given the modest effect sizes and the study’s reliance on genetic proxies rather than direct phenotypic measurements. Further replication in diverse ancestries and integration with mechanistic data will be essential to consolidate these conclusions and lay the groundwork for translational applications.
In summary, Liu et al.’s investigation decisively contributes to the intricate puzzle of psoriasis and cancer interplay, revealing selective protective genetic links to uterine corpus and prostate cancers. This challenges simplistic models of chronic inflammation as purely carcinogenic and opens exciting avenues for interdisciplinary research at the nexus of dermatology, oncology, and genetics.
As the field advances, harnessing the precision of Mendelian randomization alongside multi-omic data promises to revolutionize our understanding of how immune-mediated diseases influence cancer trajectories. This study stands as a beacon illuminating the complexity and nuance inherent in human disease biology, encouraging a paradigm shift toward genetically informed, context-dependent disease risk assessment.
Ultimately, such insights will be pivotal in refining personalized medicine frameworks, optimizing preventive care, and unlocking innovative avenues for therapy that capitalize on nature’s own genetic experiments.
Subject of Research: Associations between psoriasis and the risk of 33 common cancers investigated through Mendelian randomization using large-scale genetic datasets.
Article Title: Associations between psoriasis and risk of 33 cancers: a Mendelian randomization study
Article References:
Liu, M., Sun, Z., Tan, P. et al. Associations between psoriasis and risk of 33 cancers: a Mendelian randomization study. BMC Cancer 25, 837 (2025). https://doi.org/10.1186/s12885-025-14243-4
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-14243-4
Tags: autoimmune disorder and cancer correlationcausal relationships in psoriasis researchchronic inflammatory diseases and cancergenetic architecture of psoriasisgenetic variants in disease outcomesGWAS meta-analysis psoriasisMendelian randomization approachobservational studies limitations in cancerprotective effects of psoriasis against malignanciespsoriasis cancer risk studyskin inflammation and cancer riskSNPs and cancer susceptibility
