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Risk of Colorectal Cancer in Monoallelic and Biallelic Carriers of MYH Mutations: A Population-Based Case-Family Study

¹ Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Victoria, Australia; ² Samuel Lunenfeld Research Institute and ³ Department of Surgery, Mount Sinai Hospital; and ⁴ Cancer Care Ontario, Toronto, Ontario, Canada

Requests for reprints: Steven Gallinger, Department of Surgery, Mount Sinai Hospital, University of Toronto, Room 1225, 600 University Avenue, Toronto, Ontario, Canada. Phone: 416-586-8550; Fax: 416-586-8392. E-mail: sgallinger{at}rogers.com

Previous case-control studies have suggested that carriers of monoallelic germline mutations in the MYH gene may be at increased risk of colorectal cancer. We applied a kin-cohort design, using a modified segregation analysis, to estimate the colorectal cancer risk using 300 first-degree relatives of 39 colorectal cancer cases who were monoallelic or biallelic carriers of MYH mutations. We found that monoallelic carriers had a 3-fold increased risk of colorectal cancer (hazard ratio, 2.9; 95% confidence interval, 1.2-7.0; P = 0.02) and biallelic carriers a 50-fold increased risk (hazard ratio, 53; 95% confidence interval, 14-200; P < 0.0001). This analysis illustrates the potential of family analysis to estimate cancer risk for low-frequency mutations and, based on the proportion of relatives predicted to be carriers, we believe that this constitutes the largest study of monoallelic carriers to date. (Cancer Epidemiol Biomarkers Prev 2006;15(2):312–4)

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