An observational and genetic investigation into the association between psoriasis and risk of malignancy

• Published in: Nature communications 2024-09, Vol.15 (1), p.7952-11, Article 7952
• Main Authors: Li, Ruolin, Luo, Wenjin, Chen, Xiangjun, Zeng, Qinglian, Yang, Shumin, Wang, Ping, Hu, Jinbo, Chen, Aijun
• Format: Article
• Language: English
• Subjects: 631/208/205; 631/208/2489/68; 631/250/249/1313/1758; Annotations; Breast cancer; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Data analysis; Female; Genetic analysis; Genetic Predisposition to Disease; Genome-Wide Association Study; Humanities and Social Sciences; Humans; Investigations; Lung cancer; Lung Neoplasms - epidemiology; Lung Neoplasms - genetics; Lymphoma; Male; Malignancy; Mendelian Randomization Analysis; Middle Aged; multidisciplinary; Multifactorial Inheritance - genetics; Neoplasms - epidemiology; Neoplasms - genetics; Non-Hodgkin's lymphoma; Polymorphism, Single Nucleotide; Psoriasis; Psoriasis - epidemiology; Psoriasis - genetics; Quantitative Trait Loci; Randomization; Risk Factors; Science; Science (multidisciplinary); Skin cancer; Skin diseases; United Kingdom - epidemiology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-51824-6

The relationship between psoriasis and site-specific cancers remains unclear. Here, we aim to investigate whether psoriasis is causally associated with site-specific cancers. We use observational and genetic data from the UK Biobank, obtaining GWAS summary data, eQTL analysis data, TCGA data, and GTEx data from public datasets. We perform PheWAS, polygenic risk score analysis, and one-sample and two-sample Mendelian randomization analyses to investigate the potential causal associations between psoriasis and cancers. In the unselected PheWAS analysis, psoriasis is associated with higher risks of 16 types of cancer. Using one-sample Mendelian randomization analyses, it is found that genetically predicted psoriasis is associated with higher risks of anal canal cancer, breast cancer, follicular non-Hodgkin’s lymphoma and nonmelanoma skin cancer in women; and lung cancer and kidney cancer in men. Our two-sample Mendelian randomization analysis indicates that psoriasis is causally associated with breast cancer and lung cancer. Gene annotation shows that psoriasis-related genes, such as ERAP1, are significantly different in lung and breast cancer tissues. Taken together, clinical attention to lung cancer and breast cancer may be warranted among patients with psoriasis. The relationship between psoriasis and cancer remains unclear. Here, the authors use PheWAS, polygenic risk scores, and Mendelian randomization analyses to demonstrate that psoriasis is causally associated with lung and breast cancer.