An evaluation of the role of genetic testing in hereditary nonpolyposis colorectal cancer (HNPCC)

grantor: University of TorontoBackground. Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common form of inherited colorectal cancer (CRC). At least a subset of HNPCC families have a mismatch repair (MMR)gene mutation. Objectives. The objectives of this thesis were: (a)to evaluate the clinical differences in high risk families with (M+) and without (M$-$) a MMR gene mutation, (b) to evaluate the test characteristics of published clinical criteria, and (c) to develop new clinical criteria to better identify high risk M+ and M$-$ families. Methods. A retrospective cohort of 91 high risk families who met the Mount Sinai Registry criteria was accrued from three sources. The data were aggregated by family so that differences between M+ and M$-$ families could be examined. The test characteristics of 4 published criteria were evaluated. Using multivariate logistic regression modeling, criteria to identify high risk families with a mutation were developed. Results. Differences between M+ and M$-$ families included the mean age of earliest cancer (36.2 vs 46.4 years of age, p $<$ 0.05) within a family and mean number of right sided lesions within a family (1.7 vs 0.96/family, p $<$ 0.05). When compared to other published criteria, the Amsterdam criteria have the highest sensitivity (50%) and specificity (60%). (Abstract shortened by UMI.)M.Sc