Mendelian risk prediction models calculate the probability of a proband being a mutation carrier based on family history and known mutation prevalence and penetrance. Family history in this setting, is self-reported and is often reported with error. Various studies in the literature have evaluated misreporting of family history. Using a validation data set which includes both error-prone self-reported family history and error-free validated family history, we propose a method to adjust for misreporting of family history. We estimate the measurement error process in a validation data set (from University of California at Irvine (UCI)) using nonparametric smoothed Kaplan-Meier estimators, and use Monte Carlo integration to implement the adjustment. In this paper, we extend BRCAPRO, a Mendelian risk prediction model for breast and ovarian cancers, to adjust for misreporting in family history. We apply the extended model to data from the Cancer Genetics Network (CGN).
Braun, Danielle; Gorfine, Malka; Katki, Hormuzd A.; Ziogas, Argyrios; Anton-Culver, Hoda; and Parmigiani, Giovanni, "Extending Mendelian Risk Prediction Models to Handle Misreported Family History" (January 2014). Harvard University Biostatistics Working Paper Series. Working Paper 183.