Increased Colorectal Cancer Incidence in Obligate Carriers of Heterozygous Mutations in MUTYH

Jones, N; Vogt, S; Nielsen, M; Christian, D; Wark, PA; Eccles, D; Edwards, E; Evans, DG; Maher, ER; Vasen, HF; Hes, FJ; Aretz, S; Sampson, JR; (2009) Increased Colorectal Cancer Incidence in Obligate Carriers of Heterozygous Mutations in MUTYH. Gastroenterology, 137 (2). pp. 489-494. ISSN 0016-5085 DOI:

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BACKGROUND & AIMS: MUTYH-associated polyposis (MAP) is an autosomal recessive disorder caused by mutations in the MUTYH gene. Patients with MAP are at extremely high risk of colorectal cancer, but the risks of colorectal and other cancers in heterozygous carriers of a single MUTYH mutation are uncertain. We performed a retrospective study of cancer incidence and causes of death among obligate MUTYH heterozygote individuals. METHODS: MAP index cases were identified from polyposis registers in Germany, The Netherlands, and the United Kingdom. Cancer incidence, cancer mortality, and all-cause mortality data were collected from 347 parents of unrelated MAP index cases and the spouses of 3 index cases who were also found to be heterozygous for single MUTYH mutations. These data were compared with appropriate national sex-, age-, and period-specific population data to obtain standardized mortality ratios (SMR) and standardized incidence ratios (SIR). RESULTS: There was a 2-fold increase in the incidence of cotorectal cancer among parents of MAP cases, compared with the general population (SIR, 2.1.2; 95% confidence interval [CI]: 1.30-3.28). Their colorectal cancer mortality was not increased significantly (SMR, 1.02; 95% CI: 0.41-2.10) nor was overall cancer risk (SIR, 0.92; 95% CI: 0.70-1.18), cancer mortality (SMR, 1.12; 95% CI: 0.83-1.48), or overall mortality (SMR, 0.94; 95% CI: 0.80-1.08). CONCLUSIONS: The risk of colorectal cancer in heterozygous carriers of single MUTYH mutations who are relatives of patients with MAP is comparable with that of first-degree relatives of patients with sporadic colorectal cancer. Screening measures should be based on this modest increase in risk.

Item Type: Article
Keywords: Age Distribution, Aged, Aged, 80 and over, Colonoscopy, Colorectal Neoplasms, epidemiology, genetics, pathology, Confidence Intervals, DNA Glycosylases, genetics, DNA Mutational Analysis, Education, Medical, Continuing, Female, Genetic Predisposition to Disease, epidemiology, Genetic Screening, Heterozygote, Humans, Incidence, Male, Middle Aged, Mutation, genetics, Odds Ratio, Pedigree, Probability, Prognosis, Registries, Risk Assessment, Sex Distribution, Survival Rate
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 19394335
Web of Science ID: 268551000022


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