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Results from Mendelian randomization analyses revealed PsO and PsA did not increase the risk of basal cell carcinoma, cutaneous squamous cell carcinoma, or cutaneous melanoma.
Neither psoriasis (PsO) nor psoriatic arthritis (PsA) are causally associated with the genetic risk of skin cancer, according to findings from a recent study.
Results indicated PsA may be associated with basal cell carcinoma, although other risk factors including skin tanning, radiation-related disorders of the skin and subcutaneous tissue, and telomere length likely confounded this association.1
“While certain studies have observed an elevated risk of skin cancer associated with PsO and PsA, the precise underlying connection remains unclear, with some research even yielding difference findings,” wrote investigators.1 “A comprehensive understanding of this causal association would facilitate a deeper understanding of the underlying mechanisms driving their respective risk profiles.”
According to the US Centers for Disease Control and Prevention, skin cancer is the most common form of cancer in the US.2 Many chronic inflammatory diseases are associated with an increased risk of developing cancers. Previous studies assessing the association between PsO and PsA with skin cancer have not examined the specific mechanisms underlying the potential link, prompting further research.3
To further assess the causal association of PsO and PsA with skin cancer, Yeye Guo, MD, PhD, of Xiangya Hospital at Central South University in China, and colleagues conducted univariate and multivariate Mendelian randomization analyses of a cohort of adult patients with and without psoriatic conditions using Mendelian randomization-Egger, weighted median, random-effect inverse variance weighted, and weighted mode approaches.1
Single nucleotide polymorphisms strongly associated with PsO were obtained from a genome-wide association meta-analysis including the Psoriasis Collaborative Association Study, Kiel, Wellcome Trust Case-Control Consortium 2, Psoriasis Society Genetics Extension, and Genetic Analysis of the Psoriasis Consortium, which involved 10,588 patients with PsO and 22,806 individuals of European ancestry as controls. For PsA, the latest FinnGen release 9 gene database was employed, encompassing 3,186 cases and 240,862 controls.1
The basal cell carcinoma dataset was sourced from a genome-wide association meta-analysis encompassing 17,416 cases and 375,455 controls, primarily from the UK Biobank, with additional data for 18,982 cases and 305,750 controls incorporated from FinnGen. Investigators also obtained data for exposure factors known to be associated with an elevated risk of basal cell carcinoma, including ease of skin tanning, radiation-related disorders of the skin and subcutaneous tissue, and telomere length.1
Cutaneous squamous cell carcinoma data for 404 cases and 336,755 controls were obtained from Neale Lab and 3,251 cases and 287,157 controls were collected from FinnGen. The data for cutaneous melanoma was sourced from the UK Biobank and FinnGen, comprising a sample size of 6,744 cases and 662,146 controls.1
Upon analysis, genetically predicted PsO, per log-odds ratio increase, showed no significant association with the risk of basal cell carcinoma, cutaneous squamous cell carcinoma, and cutaneous melanoma. The odds ratios for basal cell carcinoma, cutaneous squamous cell carcinoma, and cutaneous melanoma were 1.00 (95% confidence interval [CI], 0.99-1.01; PIvw = 0.990), 0.94 (95% CI, 0.89-1.00; PIvw = 0.065), and 0.99 (95% CI, 0.98-1.01; PIvw = 0.239), respectively.1
Further analysis yielded similar results for PsA, again finding no significant association with the risk of cutaneous squamous cell carcinoma (odds ratio [OR], 1.00; 95% CI, 1.00-1.00; PIvw = 0.214) and cutaneous melanoma (OR, 1.00; 95% CI, 1.00-1.00; PIvw = 0.477). Of note, PsA exhibited a significant association with the decreased risk of basal cell carcinoma, with an odds ratio of 0.94 (95% CI, 0.90-0.99; PIvw = 0.016). However, in a multivariate regression analysis including 3 risk factors, PsA was no longer found to be associated with basal cell carcinoma, while the association of skin tanning, radiation-related disorders of the skin and subcutaneous tissue, and telomere length remained significant (all P < .05).1
“Although PsO and PsA as diseases may not inherently amplify the skin cancer risk, environmental elements like sun exposure and therapeutic interventions such as biologics and methotrexate can heighten the probability of skin cancer development. Consequently, for patients affected by PsO and PsA, especially those exposed to skin cancer risk factors, the significance of health education and routine self-examinations is greatly accentuated,” concluded investigators.1