Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study

Jenkins MA, Croitoru ME, Monga N, Cleary SP, Cotterchio M, Hopper JL, Gallinger S (2006) Risk of colorectal cancer in monoallelic and biallelic carriers of MYH mutations: a population-based case-family study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 15:312-314

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="">