Ontology highlight
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.
SUBMITTER: Baglietto L
PROVIDER: S-EPMC2815724 | biostudies-literature | 2010 Feb
REPOSITORIES: biostudies-literature
Baglietto Laura L Lindor Noralane M NM Dowty James G JG White Darren M DM Wagner Anja A Gomez Garcia Encarna B EB Vriends Annette H J T AH Cartwright Nicola R NR Barnetson Rebecca A RA Farrington Susan M SM Tenesa Albert A Hampel Heather H Buchanan Daniel D Arnold Sven S Young Joanne J Walsh Michael D MD Jass Jeremy J Macrae Finlay F Antill Yoland Y Winship Ingrid M IM Giles Graham G GG Goldblatt Jack J Parry Susan S Suthers Graeme G Leggett Barbara B Butz Malinda M Aronson Melyssa M Poynter Jenny N JN Baron John A JA Le Marchand Loic L Haile Robert R Gallinger Steve S Hopper John L JL Potter John J de la Chapelle Albert A Vasen Hans F HF Dunlop Malcolm G MG Thibodeau Stephen N SN Jenkins Mark A MA
Journal of the National Cancer Institute 20091222 3
<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]