Trace elements are a possible risk factor for pancreatic ductal adenocarcinoma (PDAC). However, their role in the occurrence and persistence of KRAS mutations remains unstudied. There appear to be no studies analyzing biomarkers of trace elements and KRAS mutations in any human cancer. We aimed to determine whether patients with KRAS mutated and nonmutated tumors exhibit differences in concentrations of trace elements. Incident cases of PDAC were prospectively identified in five hospitals in Spain. KRAS mutational status was determined through polymerase chain reaction from tumor tissue. Concentrations of 12 trace elements were determined in toenail samples by inductively coupled plasma mass spectrometry. Concentrations of trace elements were compared in 78 PDAC cases and 416 hospital‐based controls (case–control analyses), and between 17 KRAS wild‐type tumors and 61 KRAS mutated tumors (case–case analyses). Higher levels of iron, arsenic, and vanadium were associated with a statistically nonsignificant increased risk of a KRAS wild‐type PDAC (OR for higher tertile of arsenic = 3.37, 95% CI 0.98–11.57). Lower levels of nickel and manganese were associated with a statistically significant higher risk of a KRAS mutated PDAC (OR for manganese = 0.34, 95% CI 0.14–0.80). Higher levels of selenium appeared protective for both mutated and KRAS wild‐type PDAC. Higher levels of cadmium and lead were clear risk factors for both KRAS mutated and wild‐type cases. This is the first study analyzing biomarkers of trace elements and KRAS mutations in any human cancer. Concentrations of trace elements differed markedly between PDAC cases with and without mutations in codon 12 of the KRAS oncogene, thus suggesting a role for trace elements in pancreatic and perhaps other cancers with such mutations. Environ. Mol. Mutagen., 60:693–703, 2019. © 2019 Wiley Periodicals, Inc.

ImportanceThe Skin and UV Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) tool has been developed in the US to facilitate the identification of solid organ transplant recipients (SOTRs) at a higher risk of developing skin cancer. However, it has not yet been validated in populations other than the one used for its creation.ObjectiveTo provide an external validation of the SUNTRAC tool in different SOTR populations.Design, Setting, and ParticipantsThis retrospective external validation prognostic study used data from a prospectively collected cohort of European SOTRs from transplant centers at teaching hospitals in the Netherlands (1995-2016) and Spain (2011-2021). Participants were screened and followed up at dermatology departments. Data were analyzed from September to October 2021.Main Outcomes and MeasuresThe discrimination ability of the SUNTRAC tool was assessed via a competing risk survival analysis, cumulative incidence plots, and Wolbers concordance index. Calibration of the SUNTRAC tool was assessed through comparison of projected skin cancer incidences. Skin cancer diagnoses included squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma.ResultsA total of 3421 SOTRs (median age at transplant, 53 [quartile 1: 42; quartile 3: 62] years; 2132 [62.3%] men) were assessed, including 72 Asian patients (2.1%), 137 Black patients (4.0%), 275 Latinx patients (8.0%), 109 Middle Eastern and North African patients (3.2%), and 2828 White patients (82.7%). With a total of 23 213 years of follow-up time, 603 patients developed skin cancer. The SUNTRAC tool classified patients into 4 groups with significantly different risks of developing skin cancer during follow-up. Overall, the relative rate for developing skin cancer estimated using subdistribution hazard ratios (SHRs) and using the low-risk group as the reference group, increased according to the proposed risk group (medium-risk group: SHR, 6.8 [95% CI, 3.8-12.1]; P < .001; high-risk group: SHR, 15.9 [95% CI, 8.9-28.4]; P < .001; very-high–risk group: SHR, 54.8 [95% CI, 29.1-102.9]; P < .001), with a concordance index of 0.72. Actual skin cancer incidences were similar to those predicted by the SUNTRAC tool (5-year skin cancer cumulative incidence for medium-risk group: predicted, 6.2%; observed, 7.0%).Conclusions and RelevanceThe findings of this external validation prognostic study support the use of the SUNTRAC tool in European populations for stratifying SOTRs based on their skin cancer risk and also detecting patients at a high risk of developing skin cancer. This can be helpful in prioritizing and providing better screening and surveillance for these patients.

Background The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes.Objective To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. Methods Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction.Results A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression ], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality .9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression , P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR.Limitations Retrospective design and heterogeneity of SOTR cohort.