Abstract
The relationship between psoriasis and site-specific cancers remains unclear. We aimed to investigate whether psoriasis is causally associated with site-specific cancers. We used observational and genetic data from UK Biobank. We obtained genome-wide association study (GWAS) summary data, expression quantitative trait locus (eQTL) analysis data, The Cancer Genome Atlas (TCGA) data and genotype-tissue expression (GTEx) data from public datasets. We used a phenome-wide association study (PheWAS), PRS analysis, and one-sample and two-sample Mendelian randomization (MR) analysis to investigate potential causal associations between psoriasis and cancers. We added gene annotation for potential molecular associations. A total of 13463 patients with psoriasis and 463136 participants without psoriasis were included. In unselected PheWAS analysis, psoriasis was associated with higher risks of 14 types of cancer. In one-sample MR analyses, genetically predicted psoriasis was associated with higher risks of anal canal cancer (hazard ratio [HR] 1.61, 95% CI 1.12–2.32), breast cancer (HR 1.06, 95% CI 1.02–1.11) and nonmelanoma skin cancer (HR 1.07, 95% CI 1.01–1.14) in women and lung cancer (HR 1.17, 95% CI 1.04–1.32) and kidney cancer (HR 1.34, 95% CI 1.13–1.58) in men. Two-sample MR analysis indicated that psoriasis was causally associated with breast cancer (inverse variance weighted [IVW] odds ratio 1.02, 95% CI 1.01–1.03) and lung cancer (IVW odds ratio 1.12, 95% CI 1.02–1.22). Gene annotation revealed that psoriasis-related genes (such as ERAP1 and C6orf3) were significantly changed in lung and breast cancer tissues. Our findings demonstrate psoriasis is causally associated with lung cancer and breast cancer. Regular screening for lung and breast cancer might be relevant for patients with psoriasis.