NEW YORK (Reuters Health) - Solid organ transplant recipients have a "strikingly high" risk of developing Merkel cell carcinoma (MCC), and immunosuppressive medication may act synergistically with exposure to ultraviolet radiation (UVR) to increase the risk, new research hints.
"Transplant recipients should be encouraged to adopt sun safety practices and limit UVR exposure to reduce their likelihood of developing MCC and other skin cancers for which they are at exceedingly high risk," the investigators advise in a paper online now in the Journal of the National Cancer Institute.
Solid organ transplant recipients are known to have an increased risk of developing virus-related cancers, due in part from long-term immunosuppressive therapy. MCC is an aggressive skin cancer recently found to have a viral origin, but the risk of MCC after transplant is unclear.
To investigate, Dr. Christina A. Clarke, of the Cancer Prevention Institute of California in Fremont, and colleagues linked U.S. national transplant registries and population-based cancer registries. They identified a total of 110 MCC cases among 189,498 solid organ transplant recipients.
The overall incidence rate of MCC was 12.8 per 100,000 person-years. Compared to the general population, this corresponded to a nearly 24-fold increase in risk (standardized incidence ratio 23.8), the investigators say.
Incidence rates increased "steeply" with increasing age at transplant; 73% of MCC cases were in people over age 50 at transplant. MCC was more common in male transplant recipients and whites. MCC incidence rates also increased significantly with time since transplant, with more occurring 10 or more years after transplant.
Maintenance immunosuppressive therapy with azathioprine, cyclosporine, and mTOR inhibitors increased the risk for MCC. Living at lower latitude (higher UVR exposure) also increased the risk among non-Hispanic white recipients on cyclosporine and azathioprine.
"We interpret these patterns as indicating important roles in MCC development for sustained, long-term immunosuppression, UVR, and photosensitizing effects of some maintenance medications. Future studies should explore the specific interplay between carcinogenic viruses, immune dysfunction, and UVR as they relate to skin cancer etiology," the investigators conclude.
The authors of a linked editorial say this study is important for several reasons. "First, it provides a confident epidemiological association between immunosuppression and MCC, a cancer that is recognized to be associated with genomic integration of viral DNA," they write.
"Second, it offers a more precise estimate of the increased relative risk of MCC development (approximately 24-fold over healthy control patients) in transplant recipients, an ideal population for research focused on prevention, causation, and treatment of MCC," they add.
"Third, this study provides provocative but preliminary data on a possible synergistic link between sun exposure and certain immunosuppressive drugs that increase the likelihood of MCC development, supporting laboratory findings by others."
Dr. Vernon Sondak and co-authors from the Moffitt Cancer Center, Tampa, Florida, also note that the synergism between cyclosporine/azathioprine and UV exposure hints that the drugs themselves may "promote UV-associated DNA damage and/or inhibit DNA repair, increasing the risk of malignant transformation."
This hypothesis is supported by laboratory studies, but the number of MCC cases in this study (n=110) is too small to draw firm conclusions about the relative carcinogenic risk of specific drugs or combinations, the editorialists point out.
Nonetheless, they say the data suggest that in solid organ transplant recipients with a history of non-melanoma skin cancer, "extensive sun exposure, and/or fair skin, alternatives to a cyclosporine/azathioprine combination should be considered when otherwise feasible."
The study was supported by the Stanford Cancer Institute and the National Cancer Institute. The authors have no relevant disclosures.
SOURCE: http://bit.ly/1KpcZQ5 and http://bit.ly/1Kpd86g
JNCI Natl Cancer Inst 2015.
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