Contribution of the TP53 R337H mutation to the cancer burden in families with a proband with adrenocortical tumor.

1538Background: The TP53R337H mutation, a loss-of-function founder mutation in the Southern Brazilian population, predisposes children to adrenocortical tumor (ACT), choroid plexus carcinoma, and, rarely, other tumors, but its impact on adult-onset cancer remains to be determined. We describe the history of cancer in R337H carrier lineages and compare the frequency and types of cancer in carrier and noncarrier parental lineages and in selected families reported to the IARC database. Methods: The history of cancer in 55 families with a proband with ACT carrying the R337H mutation was updated yearly. Quasi-likelihood score, generalized disequilibrium, chi-square, and Fisher’s exact tests were used to analyze cancer frequency and spectrum. Results: The R337H status was determined for 175 of 179 first-degree relatives of the probands. At a median follow-up time of 9.7 years (3–32 years), new-onset cancer had been diagnosed in 12 (15%) of 81 first-degree relatives of probands in the R337H carrier lineages but ...