Risk of merkel cell carcinoma after solid organ transplantation

• Published in: JNCI : Journal of the National Cancer Institute Vol. 107; no. 2; p. dju382
• Main Authors: Clarke, Christina A, Robbins, Hilary A, Tatalovich, Zaria, Lynch, Charles F, Pawlish, Karen S, Finch, Jack L, Hernandez, Brenda Y, Fraumeni, Jr, Joseph F, Madeleine, Margaret M, Engels, Eric A
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.02.2015
• Subjects: Adult; Aged; Azathioprine - adverse effects; Carcinoma, Merkel Cell - epidemiology; Carcinoma, Merkel Cell - etiology; Cyclosporine - adverse effects; Female; Humans; Immunocompromised Host; Immunosuppressive Agents - administration & dosage; Immunosuppressive Agents - adverse effects; Incidence; Male; Middle Aged; Organ Transplantation; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - adverse effects; Poisson Distribution; Registries; Remission Induction - methods; Risk Assessment; Risk Factors; Skin Neoplasms - epidemiology; Skin Neoplasms - etiology; TOR Serine-Threonine Kinases - antagonists & inhibitors; Transplant Recipients; Ultraviolet Rays - adverse effects; United States - epidemiology; United States
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/dju382

Solid organ transplant recipients have elevated risks of virus-related cancers, in part because of long-term immunosuppression. Merkel cell carcinoma (MCC) is an aggressive skin cancer recently found to have a viral origin, but little is known regarding the occurrence of MCC after transplant. We linked the US Scientific Registry of Transplant Recipients with data from 15 population-based cancer registries to ascertain MCC occurrence among 189498 solid organ transplant recipients from 1987 to 2009. Risks for MCC following transplantation were compared with the general population using standardized incidence ratios, and Poisson regression was used to compare incidence rates according to key patient and transplant characteristics. All statistical tests were two-sided. After solid organ transplantation, overall risk of MCC was increased 23.8-fold (95% confidence interval = 19.6 to 28.7, n = 110). Adjusted risks were highest among older recipients, increased with time since transplantation, and varied by organ type (all P ≤ .007). Azathioprine, cyclosporine, and mTOR inhibitors given for maintenance immunosuppression increased risk, and non-Hispanic white recipients on cyclosporine and azathioprine experienced increasing MCC risk with lower latitude of residence (ie, higher ultraviolet radiation exposure, P = .012). MCC risk is sharply elevated after solid organ transplant, likely resulting from long-term immunosuppression. Immunosuppressive medications may act synergistically with ultraviolet radiation to increase risk.