This is the program for the 2010 Joint Statistical Meetings in Vancouver, British Columbia.

Abstract Details

Activity Number: 642
Type: Invited
Date/Time: Thursday, August 5, 2010 : 10:30 AM to 12:20 PM
Sponsor: SSC
Abstract - #306129
Title: Multistate Modeling Approaches for Estimating Disease Risk in Gene Mutation Carriers from Family Data
Author(s): Karen Kopciuk*+ and Yun-Hee Choi and Laurent Briollais and Patrick Parfrey and Jane Green
Companies: Alberta Health Services and The University of Western Ontario and Samuel Lunenfeld Research Institute and Memorial University and Memorial University
Address: 1331 - 29 Street NW, Calgary, AB, T2N 4N2, Canada
Keywords: multi-state models ; disease risk (penetrance) ; Expectation-Maximization (EM) algorithm ; missing genotype data ; multiple phenotypes ; disease screening

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) results in multiple cancers within the same family so understanding the patterns of various cancers among individuals can help dissect the genetic origin of the disease and predict future events in susceptible individuals. We employ progressive and illness-death multi-state models to estimate age-specific penetrance estimates of developing successive phenotypes and to assess the impact of interventions in pedigree data. An EM algorithm is developed to estimate all regression model parameters by inferring missing genotypes; our methods were applied to a retrospective cohort of 12 HNPCC families from Newfoundland who harbour a founder mutation. We found the modulating time scale term unnecessary, lifetime penetrance for a second cancer high (70% for males, 50% for females) and hazard ratios of 2nd to 1st cancer in carriers fell with age.

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