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To the Editor: Long duration of patients on hemodialysis is a large risk for the development of renal cell carcinoma compared to general patients. Acquired cystic kidney develops in up to 90% of long-term hemodialysis patients, and the carcinoma occurs via the formation of the acquired cyst as a precancerous region derived from the proximal tubular cell, a progenitor cell of the carcinoma [1]. Thus, determining tumor suppressor gene(s) inactivated in the acquired cyst may be a key clue leading to the risk reduction in the development of the renal cell carcinoma. We have previously reported that connexin 32, a member of gap junction, acts as a tumor suppressor gene in renal cell carcinoma from hemodialysis patients [2]. Hypermethylation of CpG islands in the promoter regions is considered as a mechanism of transcriptional inactivation other than mutations and/or deletions in the genes [3]. The loss of function for the connexin 32 gene depends on the hypermethylation because mutation and deletions appear to be rare [3]. We have found that silencing of the connexin 32 gene through the hypermethylation frequently occurs in the acquired cyst and renal cell carcinoma but not normal renal tissue [4]. On the other hand, other tumor suppressor genes for renal cell carcinoma have been down-regulated through the hypermethylation only in the renal cell carcinoma but not the acquired cyst [4]. These results suggest that loss of connexin 32 function through the hypermethylation in the acquired cyst is a trigger for the development of the renal cell carcinoma at the early carcinogenic process.

To the Editor: Maintenance hemodialysis patients with end-stage renal disease have an increased incidence of renal cell carcinoma compared with the general population1. Since the pathogenic mechanisms responsible for the increased renal cell carcinoma in maintenance hemodialysis patients have not been fully elucidated, it is worth understanding the carcinogenic process to establish new diagnostic and preventive procedures for renal cell carcinoma.