Madeleine, Margaret MResler, Alexa Jean2014-10-202015-12-142014-10-202014Resler_washington_0250E_13077.pdfhttp://hdl.handle.net/1773/26941Thesis (Ph.D.)--University of Washington, 2014Background: Non-melanoma skin cancer (NMSC) is the most frequent malignancy occurring among renal transplant recipients (RTR). The aim of this study was to assess whether exposures in the early post-transplant period, namely serum concentrations of 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) and trough concentrations of tacrolimus (TAC) and mycophenolic acid (MPA), were associated with the risk of NMSC occurring 1 year or more after renal transplant. Methods: This prospective study included 441 adults from the Skin Cancer after Organ Transplant study who received a renal (kidney or kidney and pancreas) transplant at the University of Washington Medical Center between 2005 and 2011. Data were collected through mailed and in-person questionnaires with telephone follow-up, review of medical records, and abstraction of pathology reports. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using Cox proportional hazards models to estimate the relative risk of developing SCC, BCC, and any NMSC (SCC or BCC). Results: We observed statistically significant associations between 25(OH)D concentrations and the risk of SCC (p=0.05) and SCC or BCC (p=0.05), though not BCC (p=0.10). Participants with an average 25(OH)D of 20+ vs. <20 ng/mL over the first 2 months post-transplant had a reduced risk of SCC (HR 0.32, 95% CI 0.10-0.99) and SCC or BCC (HR 0.42, 95% CI 0.18-1.00). When comparing RTR with average PTH concentrations of 88+ vs. <88 pg/mL over the first 2 months post-transplant, PTH was not significantly associated with the risk of SCC (HR 1.68, 95% CI 0.59-4.81), BCC (HR 1.74, 95% CI 0.67-4.55), or SCC or BCC (HR 1.60, 95% CI 0.74-3.47). In secondary analyses, we observed that continuous linear PTH was significantly associated with an increased risk of BCC (HR 1.04, 95% CI 1.02-1.06 per 10 pg/mL, p=0.01) and SCC or BCC (HR 1.03, 95% CI 1.01-1.05 per 10 pg/mL, p=0.01). We did not observe associations between average TAC trough concentrations over the first 2 months post-transplant and the risk of SCC, BCC, or SCC or BCC. Conclusions: Our findings do not suggest strong associations between TAC trough concentrations and the risk of NMSC among RTR. We did not observe statistically significant associations between PTH concentrations and NMSC risk in our primary analyses in which we compared RTR with PTH concentrations of 88+ vs. <88 pg/mL. When modeling PTH as a continuous linear exposure in secondary analyses, we observed that higher PTH concentrations among RTR may increase NMSC risk after transplant. Results from this study suggest that sufficient 25(OH)D concentrations in the early post-transplant period could decrease the risk of NMSC following renal transplant. Further studies are warranted that examine this association. If our results were replicated such findings could suggest that monitoring vitamin D concentrations, and possibly administering vitamin D supplementation, may aid in reducing the incidence of post-transplant NMSC.application/pdfen-USCopyright is held by the individual authors.immunosuppressive medications; non-melanoma skin cancer; parathyroid hormone; renal transplant; vitamin DPublic healthEpidemiologyepidemiologyThesis