The epidemiology and molecular characterization of colorectal cancer in eastern Newfoundland

• Main Author: Curtis, Fiona K.
• Format: Thesis
• Language: English
• Published: Memorial University of Newfoundland 2003
• Subjects: Newfoundland
• Online Access: https://research.library.mun.ca/10368/; https://research.library.mun.ca/10368/1/Curtis_Fiona.pdf

Background: Hereditary Non-Polyposis Colon Cancer (HNPCC) is a dominantly inherited disorder caused by germ-line defects of mismatch repair (MMR) genes. HNPCC can be diagnosed using clinical and genetic criteria. Few population-based studies have been undertaken to determine the genetic basis of CRC. The purpose of this pilot project was to determine the proportion of hereditary vs. sporadic CRC cases on the Avalon Peninsula (AP) of Newfoundland and to determine the genetic basis of disease in hereditary cases. -- Methods: The population studied was identified through the Newfoundland Cancer Treatment and Research Foundation (NCTRF) registry, the meditech system (a hospital reporting tool), and pathology reports. One hundred and sixty-eight potential probands were identified, diagnosed in either 1997 or 1998, between the ages of 20-69, and residing on the AP. Probands, or an appropriate next of kin if a proband was deceased, were interviewed to determine family history of cancer. Contact was made with 158 eligible participants of which one hundred and six (67%) agreed to participate in the study. The final number of study subjects was 79, which was 74.5% of those who agreed to participate. The NCTRF registry and a review of medical charts were used for the collection of baseline characteristics which included demographic and clinical data. -- Probands were classified by their family history using the Amsterdam Criteria (AC), Amsterdam II Criteria, and several other criteria to identify familial risk of HNPCC. Microsatellite analysis (n= 74) and immunohistochemistry analysis (n= 71) for hMLH1, hMSH2, and hMSH6 was completed on proband's normal and tumour DNA. We also examined the diagnostic utility of microsatellite analysis and of protein expression to identify High Risk (HR) families, in comparison to Low Risk (LR) families. -- Results: Twenty-two (28.2%) families were considered HR with 6 families fulfilling the AC I, 1 family fulfilling the AC II, and 15 families fulfilling our Age and Cancer Modified AC ...