Mev Dominguez-Valentin from The Department of Tumor Biology is the first author of the article “Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: A report from the Prospective Lynch Syndrome Database”, recently published in eClinicalMedicine, part of The Lancet Discovery Science.
She is the PI of The Prospective Lynch Syndrome Database (PLSD), that is a Norwegian initiative and the largest world-wide prospective observational study of people identified to carry a pathogenic mismatch repair (path_MMR) variant, and these people are under frequent endoscopic surveillance. The PLSD is a prospective observational study without a control group. It was designed in 2012 and is updated up to October 2022. Data for 8,500 carriers of path_MMR variants from 25 countries have been included, providing 71,713 years of follow up.
Lynch syndrome (LS) is characterised by the development of colorectal cancer, endometrial cancer and various other cancers. It is caused by germline pathogenic variants within the mismatch repair genes (path_MMR), with each variant having different penetrance and expressivity. Previously, outcomes from interventions, including colonoscopy, have been reported as cancer incidences, not as survival. A reduction of colorectal cancer incidence by colonoscopy surveillance has not been documented for this group, and there are limited data regarding risks for other cancer types, and on the effectiveness of wider cancer surveillance in individuals with Lynch syndrome.
Our study described that in carriers of path_MMR variants undergoing colonoscopy surveillance, colorectal cancer was frequent, but associated with low mortality, while some other cancers, notably bile duct, pancreatic and brain tumors, were associated with high mortality, and that more deaths followed non-colorectal rather than colorectal cancers.
Our study suggest that prevention and treatment of non-colorectal cancers should be prioritised to further reduce mortality in LS individuals.
Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database
Mev Dominguez-Valentin et al.
Published in eClinicalMedicine, part of The Lancet Discovery Science.
Available online 20 March 2023, 101909