Background/purpose: Mutations of the RET proto-oncogene are responsible for the development of inherited multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma (MTC). RET mutations are encountered in patients with Hirschsprung's disease (HD). We hypothesized that the incidence of MTC is increased in patients with HD.
Methods: Patients treated for HD at the Children's Hospital, University of Helsinki, during 1939 and 1986 were surveyed for cancer using the population-based countrywide Finnish Cancer Registry from 1967 to 2000. The number of observed cancer cases and that of person-years at risk were counted. The expected number of cancer cases was extrapolated from national cancer incidence rates. To calculate the standardized incidence ratios (SIRs), the observed number of cancer cases was divided by the expected number of cancer cases.
Results: One hundred fifty-six patients (132 males) with HD were identified. The mean length of patient follow-up was 30.9 years. Seven cases of cancer were observed (SIR, 3.5; 95% CI, 1.4-7.3). Two patients developed MTC (SIR, 550; 95% CI, 67-2000). The cases of MTC occurred in male patients at the ages of 34 and 37 years. No patient developed pheochromocytoma.
Conclusions: In this study, we report for the first time an increased risk of MTC occurring in patients treated for HD. The increased risk may be attributed to mutations of the RET proto-oncogene shared by MTC and HD. These findings warrant further studies concerning screening for MTC-type RET mutations in patients with HD.