title: Risk of merkel cell carcinoma after solid organ transplantation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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). tina@cpic.org.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Clarke
authors.affiliation: 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).
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Robbins
authors.affiliation: 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).
authors.forename: Zaria
authors.initials: Z
authors.lastname: Tatalovich
authors.affiliation: 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).
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.affiliation: 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).
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pawlish
authors.affiliation: 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).
authors.forename: Jack L
authors.initials: JL
authors.lastname: Finch
authors.affiliation: 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).
authors.forename: Brenda Y
authors.initials: BY
authors.lastname: Hernandez
authors.affiliation: 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).
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Fraumeni
authors.affiliation: 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).
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Madeleine
authors.affiliation: 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).
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engels
mesh_terms: D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000009:adverse effects; D015266:Carcinoma, Merkel Cell / Q000453:epidemiology* / Q000209:etiology; D016572:Cyclosporine / Q000009:adverse effects; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016012:Poisson Distribution; D012042:Registries; D012074:Remission Induction / Q000379:methods; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000209:etiology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D066027:Transplant Recipients; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014481:United States / Q000453:epidemiology
chemical_list: D007166:Immunosuppressive Agents; D017319:Photosensitizing Agents; D016572:Cyclosporine; D058570:TOR Serine-Threonine Kinases; D001379:Azathioprine