Leiden University Scholarly Publications

Dwyer, A.J.; Murphy, C.C.; Boland, C.R.; Garcia, R.; Hampel, H.; Limburg, P.; ... ; Ahnen, D. 2019

A Summary of the Fight Colorectal Cancer Working Meeting: Exploring Risk Factors and Etiology of Sporadic Early-Age Onset Colorectal Cancer

Article / Letter to editor

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Anttila, V.; Bulik-Sullivan, B.; Finucane, H.K.; Walters, R.K.; Bras, J.; Duncan, L.; ... ; Zayats 2018

Analysis of shared heritability in common disorders of the brain

Article / Letter to editor

open access

Bos, I.; Verhey, F.R.; Ramakers, I.H.G.B.; Jacobs, H.I.L.; Soininen, H.; Freund-Levi, Y.; ... ; Vos, S.J.B. 2017

Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline

Article / Letter to editor

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Baglietto, L.; Lindor, N.M.; Dowty, J.G.; White, D.M.; Wagner, A.; Garcia, E.B.G.; ... ; Dutch Lynch Syndrome Study Grp 2010

Risks of Lynch Syndrome Cancers for MSH6 Mutation Carriers

Article / Letter to editor

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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... Show moreBackground 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. Show less