Solid organ transplant recipients, who are medically immunosuppressed to prevent graft rejection, have increased melanoma risk, but risk factors and outcomes are incompletely documented. We evaluated melanoma incidence among 139,991 non-Hispanic white transplants using linked US transplant-cancer registry data (1987-2010). We used standardized incidence ratios (SIRs) to compare incidence with the general population and incidence rate ratios (IRRs) from multivariable Poisson models to assess risk factors. Separately, we compared post-melanoma survival among transplant recipients (n=182) and non-recipients (n=131,358) using multivariable Cox models. Among transplant recipients, risk of invasive melanoma (n=519) was elevated (SIR=2.20, 95% CI 2.01-2.39), especially for regional stage tumors (SIR=4.11, 95% CI 3.27-5.09). Risk of localized tumors was stable over time after transplantation but higher with azathioprine maintenance therapy (IRR=1.35, 95% CI 1.03-1.77). Risk of regional/distant stage tumors peaked within 4 years following transplantation and increased with polyclonal antibody induction therapy (IRR=1.65, 95% CI 1.02-2.67). Melanoma-specific mortality was higher among transplant recipients than non-recipients (hazard ratio 2.98, 95% CI 2.26-3.93). Melanoma exhibits increased incidence and aggressive behavior under transplant-related immunosuppression. Some localized melanomas may result from azathioprine, which acts synergistically with UV radiation, whereas T-cell-depleting induction therapies may promote late-stage tumors. Our findings support sun safety practices and skin screening for transplant recipients.
Bibliographical noteFunding Information:
This research was supported in part by the Intramural Research Program of the National Cancer Institute. We gratefully acknowledge the support and assistance provided by individuals at the Health Resources and Services Administration (Monica Lin), the SRTR (Ajay Israni, Paul Newkirk), and the following cancer registries: the states of California, Colorado (Jack Finch), Connecticut (Lou Gonsalves), Georgia (Rana Bayakly), Hawaii, Iowa, and Illinois (Lori Koch), Michigan (Glenn Copeland), New Jersey (Xiaoling Niu), New York and North Carolina (Chandrika Rao), Texas (Melanie Williams), and Utah (Janna Harrell), and the Seattle-Puget Sound area of Washington (Margaret Madeleine). We also thank analysts at Information Management Services for programming support (David Castenson, Matthew Chaloux, Michael Curry, and Ruth Parsons). The SRTR is currently operated under the contract number HHSH250201000018C (Health Resources and Services Administration) by the Minneapolis Medical Research Foundation, Minneapolis, MN, USA. During the initial period when registry linkages were performed, the SRTR was managed by Arbor Research Collaborative for Health in Ann Arbor, MI, USA (contract number HHSH234200537009C). The following cancer registries were supported by the SEER Program of the National Cancer Institute: California (contract numbers HHSN261201000036C, HHSN261201000035C, and HHSN261201000034C), Connecticut (HHSN261201000024C), Hawaii (HHSN261201000037C, N01-PC-35137, and N01-PC-35139), Iowa (HSN261201000032C and N01-PC-35143), New Jersey (HHSN261201300021I, N01-PC-2013-00021), Seattle-Puget Sound (N01-PC-35142), and Utah (HHSN2612013000171). The following cancer registries were supported by the National Program of Cancer Registries of the Centers for Disease Control and Prevention: California (agreement 1U58 DP000807-01), Colorado (U58 DP000848-04), Georgia (5U58DP003875-01), Illinois (5U58DP003883-03), Maryland (U58DP12-1205 3919-03), Michigan (5U58DP003921-03), New Jersey (5U58/DP003931-02), New York (U58DP003879), North Carolina (U58DP000832), and Texas (5U58DP000824-04). Additional support was provided by the states of California, Colorado, Connecticut, Illinois, Iowa, Massachusetts (Massachusetts Cancer Prevention and Control Cooperative Agreement 5458DP003920), New Jersey, New York (including the Cancer Surveillance Initiative), Texas, Utah, and Washington, as well as the University of Utah and Fred Hutchinson Cancer Research Center in Seattle, WA, USA.
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