Journal
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
Volume 102, Issue 3, Pages 193-201Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/jnci/djp473
Keywords
-
Categories
Funding
- National Cancer Institute, National Institutes of Health [CA-95-011, R01-CA67941, -CA16058, CA67941, CA16058]
- Cancer Research UK [C348/A8896]
- CORE
- Medical Research Council [G0000657-53203]
- Scottish Executive Chief Scientist's Office [K/OPR/2/2/D333]
- MRC [MC_U127527198] Funding Source: UKRI
- Chief Scientist Office [CZB/4/449] Funding Source: researchfish
- Medical Research Council [MC_U127527198] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available