Association Between Renal Cell Carcinoma and Myelodysplastic Syndromes: Epigenetic Underpinning?

After clinical observations of patients with a personal history of both renal cell carcinoma (RCC) and myelodysplastic syndromes (MDSs), we sought to explore a potential association between the 2, using Mayo Clinic's ‘Advanced Cohort Explorer’ database. The prevalence of MDS in patients > 65 years with a personal history of nephrectomy for RCC was ≈8.4 times that of the age-concordant general population based on the Dusseldorf registry (28/6490 or 395/100,000 vs. ≈47/100,000; P < .001), and 3.07 times that of the age-concordant patient population at Mayo Clinic (28/6490 or 395/100,000 vs. 128.4/100,000; P < .001). Given the degree of association, this information is important for the development of survivorship care plans for patients with RCC. To our knowledge, this is the first study describing the link between RCC and MDSs. Background: Renal cell carcinoma (RCC) and certain myeloid malignancies are both characterized by widespread aberrant DNA hypermethylation. After clinical observations of patients with a personal history of both malignancies, we sought to explore a potential association, and to describe the clinical characteristics of these patients. Patients and Methods: Mayo Clinic's ‘Advanced Cohort Explorer’ database was used to identify patients with a history of both malignancies. Clinical features and long-term outcome were abstracted. Prevalence of myelodysplastic syndromes (MDSs) in patients ≥ 65 years with a personal history of nephrectomy for RCC was then compared with the prevalence of MDSs in the Dusseldorf MDS registry and the general patient population at Mayo Clinic, using 1-sample test of proportions. Results: A total of 59 patients with a diagnosis of both RCC and myeloid malignancy were identified. The myeloid malignancies included 38 MDSs, 12 acute myelogenous leukemia, and 9 myeloproliferative neoplasms. The cohort was characterized by marked male predominance (4.4:1). The median age at RCC diagnosis was 64 years (range, 37-87 years), and for myeloid malignancy was 75 years (range, 44-90 years). Prevalence of MDS in patients > 65 years with a personal history of nephrectomy for RCC was ≈ 8.4 times that of the age-concordant general population based on the Dusseldorf registry (28/6490 or 395/100,000 vs. ≈ 47/100,000; P < .001), and 3.07 times that of the age-concordant patient population at Mayo Clinic (28/6490 or 395/100,000 vs. 128.4/100,000; P < .001). Conclusions: We observed a strong association between RCC and MDS. Patients with a history of RCC appear to have a substantially increased risk of developing MDS compared with the general population.