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Title: On the utility of a comprehensive family history of colorectal cancer improve risk prediction Authors:  Yingye Zheng - Fred Hutchinson Cancer Research Cener (United States) [presenting]
Abstract: Family history of colorectal cancer (CRC) is a strong and well-established risk factor for CRC. To date, however, family history (FH) of the disease is generally only broadly categorized (usually as present or absent) in most risk prediction models. We investigated the utility of a CRC risk model that incorporates a comprehensive family history of CRC as well as information on known genetic and environmental risk factors and personal characteristics. We used data from the Colon Cancer Family Registry (CCFR). A familial risk profile (FRP) score, a probability index of absolute risk for lifetime CRC was estimated based on family structure, age of onset for affected relatives and the polygenic effect of MLH1, MSH2, MSH6, PMS2 and MUTYH using \textit{modified segregation analysis}, an adapted previous approach used as a measure of family history in the risk model. The primary endpoint was CRC diagnosis within 5-year after baseline. We used calibration plots to compare the predicted 5-year absolute risks with the observed cumulative incidence rates. Receiver Operating Characteristic (ROC) curve analyses were conducted to assess the discriminatory capacity for separating subjects with and without a CRC diagnosis within 5 years, accounting for censoring and competing risk.