Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies.
Dr Pål Møller and colleagues from Norway established more robust estimates in patients undergoing prospective cancer surveillance.
The research team undertook a multicenter study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2.
Standardized information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene.
The researchers found that 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13,782 observation years.
The team observed that 314 patients developed cancer, mostly colorectal, endometrial, and ovarian.
|The 10-year crude survival was 91% if the first cancer was colorectal|
Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers.
The research team observed that among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively.
The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%.
The team found that the cumulative incidence for ovarian cancer was 11%, 15%, 0% and 0%.
The researchers found that the 10-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian.
Dr Møller's team concludes, "The 4 Lynch syndrome-associated genes had different penetrance and expression."
"Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths."
"Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome."