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Type: Journal article
Title: Risks of Lynch Syndrome cancers for MSH6 mutation carriers
Author: Suthers, G.
Citation: Journal of the National Cancer Institute, 2010; 102(3):193-201
Publisher: Oxford Univ Press Inc
Issue Date: 2010
ISSN: 0027-8874
Statement of
Laura Baglietto... Dutch Lynch Syndrome Study Group... Graeme Suthers... et al.
Abstract: Background: Germline mutations in MSH6 account for 10%–20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain. Methods: We identified 113 families of MSH6 mutation carriers from five countries that we ascertained through family cancer clinics and population-based cancer registries. Mutation status, sex, age, and histories of cancer, polypectomy, and hysterectomy were sought from 3104 of their relatives. Age-specific cumulative risks for carriers and hazard ratios (HRs) for cancer risks of carriers, compared with those of the general population of the same country, were estimated by use of a modified segregation analysis with appropriate conditioning depending on ascertainment. Results: For MSH6 mutation carriers, the estimated cumulative risks to ages 70 and 80 years, respectively, were as follows: for colorectal cancer, 22% (95% confidence interval [CI] = 14% to 32%) and 44% (95% CI = 28% to 62%) for men and 10% (95% CI = 5% to 17%) and 20% (95% CI = 11% to 35%) for women; for endometrial cancer, 26% (95% CI = 18% to 36%) and 44% (95% CI = 30% to 58%); and for any cancer associated with Lynch syndrome, 24% (95% CI = 16% to 37%) and 47% (95% CI = 32% to 66%) for men and 40% (95% CI = 32% to 52%) and 65% (95% CI = 53% to 78%) for women. Compared with incidence for the general population, MSH6 mutation carriers had an eightfold increased incidence of colorectal cancer (HR = 7.6, 95% CI = 5.4 to 10.8), which was independent of sex and age. Women who were MSH6 mutation carriers had a 26-fold increased incidence of endometrial cancer (HR = 25.5, 95% CI = 16.8 to 38.7) and a sixfold increased incidence of other cancers associated with Lynch syndrome (HR = 6.0, 95% CI = 3.4 to 10.7). Conclusion: We have obtained precise and accurate estimates of both absolute and relative cancer risks for MSH6 mutation carriers.
Keywords: Dutch Lynch Syndrome Study Group; Humans; Neoplasms; Colorectal Neoplasms, Hereditary Nonpolyposis; Endometrial Neoplasms; DNA-Binding Proteins; Registries; Incidence; Risk Assessment; Risk Factors; Mutagenesis, Insertional; Age Factors; Sex Factors; Age Distribution; Sex Distribution; Gene Deletion; Heterozygote; Germ-Line Mutation; Adult; Aged; Aged, 80 and over; Middle Aged; Canada; United States; Australia; Europe; New Zealand; Female; Male
Rights: © The Author 2009. Published by Oxford University Press.
RMID: 0020094958
DOI: 10.1093/jnci/djp473
Appears in Collections:Paediatrics publications

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