This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Woods, M. O. Articles by Parfrey, P. S. Search for Related Content PubMed PubMed Citation Articles by Woods, M. O. Articles by Parfrey, P. S.

High Frequency of Hereditary Colorectal Cancer in Newfoundland Likely Involves Novel Susceptibility Genes

Authors' Affiliations: Departments of ¹ Genetics, ² Clinical Epidemiology, and ³ Pathology, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada and ⁴ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

Requests for reprints: Michael Woods, Discipline of Genetics, Memorial University of Newfoundland, Health Sciences Centre, Room 4333, 300 Prince Philip Drive, St. John's, Newfoundland, Canada A1B 3V6. Phone: 709-777-7334; Fax: 709-777-7497; E-mail: mwoods{at}mun.ca.

Purpose: Newfoundland has one of the highest rates of colorectal cancer in North America. The most common hereditary form of colorectal cancer is hereditary nonpolyposis colorectal cancer caused by mutations in genes involved in mismatch repair. Our purpose was to determine the proportion of hereditary colorectal cancer and to determine the genetic basis of disease in both population and clinically referred cohorts from Newfoundland.

Experimental Design: Seventy-eight colorectal cancer patients were accrued over a 2-year period from the Avalon Peninsula of Newfoundland. We also examined 31 hereditary nonpolyposis colorectal cancer–like families, which had been referred to the Provincial Medical Genetics Program. Tumors from probands were tested by immunohistochemistry for deficiencies in MLH1, MSH2, and MSH6 proteins and tested for DNA microsatellite instability. Mutation analyses of MLH1, MSH2, and MSH6 were undertaken by direct sequencing and an assay to detect deletions, amplifications, and rearrangements in MSH2 and MLH1.

Results: We identified eight population-based families that fulfill the Amsterdam I or II criteria, 4 (50%) of which seem to have hereditary cancer not attributable to the most commonly mutated mismatch repair genes. In addition, in 16 of 21 (76%) referred families fulfilling Amsterdam I or II criteria, no mutations were found in the three most commonly altered mismatch repair genes, and tumor analyses corroborated these findings.

Conclusions: It seems that strong and novel genetic causes of hereditary colorectal cancer are responsible for a high proportion of colorectal cancer in this population. Conditions are suitable for the identification of these genes by linkage studies of large Newfoundland cancer families.

This article has been cited by other articles:

				M. Mrkonjic, S. Raptis, R. C. Green, N. Monga, D. Daftary, E. Dicks, H.B. Younghusband, P. S. Parfrey, S. S. Gallinger, J. R. McLaughlin, et al. MSH2 118T>C and MSH6 159C>T promoter polymorphisms and the risk of colorectal cancer Carcinogenesis, December 1, 2007; 28(12): 2575 - 2580. [Abstract] [Full Text] [PDF]

				P. T. Campbell, L. Edwards, J. R. McLaughlin, J. Green, H. B. Younghusband, and M. O. Woods Cytochrome P450 17A1 and Catechol O-Methyltransferase Polymorphisms and Age at Lynch Syndrome Colon Cancer Onset in Newfoundland Clin. Cancer Res., July 1, 2007; 13(13): 3783 - 3788. [Abstract] [Full Text] [PDF]