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).



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