Azathioprine Increases the Risk of Non‐Melanoma Skin Cancer Among Organ Transplant Recipients; an Updated Systematic Review and Meta‐Analysis

BACKGROUND: Azathioprine (AZA) is a purine antimetabolite immunosuppressant that prevents the body from rejecting transplanted organs and is used in organ transplant recipients (OTRs). This study aimed to conduct a meta-analysis to determine whether AZA usage has an increased risk of skin cancer in OTRs. METHODS: To explore the association between AZA usage and skin cancer through observational studies we conducted a systematic search across PubMed, Scopus, and Web of Science databases. A random effects model, subgroup analysis, and heterogeneity assessment were used for meta-analysis. The quality of the included studies was assessed using the Newcastle Ottawa scale checklist. RESULTS: A total of 27 studies with 21 405 patients were included to the quantitative analysis. the overall summary estimate for non-melanoma skin cancer (NMSC) risk in relation to AZA treatment according Odds ratio (OR) estimates, relative risk (RR) estimates and hazard ratio (HR) estimates were 1.83 (95% confidence interval (CI): 1.22, 2.75), 2.09 (CI: 1.41, 3.10), and 1.12 (CI: 0.93, 1.34), respectively. There was a substantial heterogeneity between studies in all types of OR estimates (I2 = 80.75%), RR estimates (I2 = 65.58%) and HR estimates (I2 = 54.63%). In the subgroup analysis, there was a significant increase in squamous cell carcinoma (SCC) risk in all three estimate effects while regarding basal cell carcinoma (BCC) none of them were significant. CONCLUSION: Our findings indicate that OTRs treated with AZA are at an increased risk for SCC and NMSC. Therefore, it is recommended to prioritize monitoring for skin cancer in OTRs treated with AZA.