Clarke Christina A, Robbins Hilary A, Tatalovich Zaria, Lynch Charles F, Pawlish Karen S, Finch Jack L, Hernandez Brenda Y, Fraumeni Joseph F, Madeleine Margaret M, Engels Eric A
Cancer Prevention Institute of California, Fremont, CA (CAC); Department of Health Research and Policy, Stanford University School of Medicine and Stanford Cancer Institute, Palo Alto, CA (CAC); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD (HAR, ZT, JFFJr, EAE); Department of Epidemiology, University of Iowa, Iowa City, IA (CFL); New Jersey State Cancer Registry, New Jersey Department of Health, Trenton, NJ (KSP); Colorado Central Cancer Registry, Colorado Department of Public Health and Environment, Denver, CO (JLF); University of Hawaii Cancer Center, Honolulu, HI (BYH); Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA (MMM); Department of Epidemiology, University of Washington, Seattle, WA (MMM).
J Natl Cancer Inst. 2015 Jan 8;107(2). doi: 10.1093/jnci/dju382. Print 2015 Feb.
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.
实体器官移植受者患病毒相关癌症的风险升高，部分原因是长期免疫抑制。默克尔细胞癌（MCC）是一种侵袭性皮肤癌，最近发现其起源于病毒，但关于移植后MCC的发生情况知之甚少。
我们将美国移植受者科学登记处与15个基于人群的癌症登记处的数据相链接，以确定1987年至2009年间189498名实体器官移植受者中MCC的发生情况。使用标准化发病率比将移植后发生MCC的风险与普通人群进行比较，并使用泊松回归根据关键患者和移植特征比较发病率。所有统计检验均为双侧检验。
实体器官移植后，MCC的总体风险增加了23.8倍（95%置信区间=19.6至28.7，n=110）。调整后的风险在老年受者中最高，随移植后时间增加而增加，且因器官类型而异（所有P≤0.007）。用于维持免疫抑制的硫唑嘌呤、环孢素和mTOR抑制剂会增加风险，使用环孢素和硫唑嘌呤的非西班牙裔白人受者随着居住纬度降低（即紫外线辐射暴露增加），MCC风险增加（P=0.012）。
实体器官移植后MCC风险急剧升高，可能是长期免疫抑制所致。免疫抑制药物可能与紫外线辐射协同作用增加风险。
