Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study.
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.
Jenkins
Mark A
MA
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Victoria, Australia.
Croitoru
Marina E
ME
Monga
Neerav
N
Cleary
Sean P
SP
Cotterchio
Michelle
M
Hopper
John L
JL
Gallinger
Steven
S
D000328:Adult; D000368:Aged; D000483:Alleles; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D004260:DNA Repair; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods
D018995:Myosin Heavy Chains