Lifetime cancer risks of PTEN mutation carriers - Response

摘要

We thank Daniels and colleagues for their comments on our report (1). Given that the Cleveland Clinic is the main referral center of patients with germline PTEN mutations in the United States, it is certainly possible that ascertainment bias may exist, an issue we acknowledged in our report. Referral bias is an inherent challenge for the study of rare genetic disorders, but clearly a population-based approach for evaluating such a rare syndrome would be impractical. We also agree that this bias would be ideally addressed by prospective follow-up of affected individuals, an effort we are currently undertaking. The Kaplan-Meier method was selected because of its widespread use in other studies evaluating lifetime cancer risks in genetic syndromes. The other methods referenced by Daniels and colleagues require either long-term follow-up or recruitment of several members within each family, making these models incompatible with this study's design and patient population.