Cancer Management and Research (Jan 2023)
A Focused Clinical Review of Lynch Syndrome
Abstract
Demetra Georgiou,1 Laura Monje-Garcia,2,3 Tracie Miles,4 Kevin Monahan,2,5 Neil AJ Ryan6,7 1Genomics and Personalised Medicine Service, Charing Cross Hospital, London, UK; 2The St Mark’s Centre for Familial Intestinal Cancer Polyposis, St Mark’s Hospital, London, UK; 3School of Public Health, Imperial College, London, UK; 4South West Genomics Medicine Service Alliance, Bristol, UK; 5Department of Gastroenterology, Imperial College, London, UK; 6Department of Gynaecological Oncology, Royal Infirmary of Edinburgh, Edinburgh, UK; 7The College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UKCorrespondence: Neil AJ Ryan, Department of Gynaecology Oncology, Royal Infirmary of Edinburgh, Edinburgh, UK, Email [email protected]: Lynch syndrome (LS) is an autosomal dominant condition that increases an individual’s risk of a constellation of cancers. LS is defined when an individual has inherited pathogenic variants in the mismatch repair genes. Currently, most people with LS are undiagnosed. Early detection of LS is vital as those with LS can be enrolled in cancer reduction strategies through chemoprophylaxis, risk reducing surgery and cancer surveillance. However, these interventions are often invasive and require refinement. Furthermore, not all LS associated cancers are currently amenable to surveillance. Historically only those with a strong family history suggestive of LS were offered testing; this has proved far too restrictive. New criteria for testing have recently been introduced including the universal screening for LS in associated cancers. This has increased the number of people being diagnosed with LS but has also brought about unique challenges such as when to consent for germline testing and questions over how and who should carry out the consent. The results of germline testing for LS can be complicated and the diagnostic pathway is not always clear. Furthermore, by testing only those with cancer for LS we fail to identify these individuals before they develop potentially fatal pathology. This review will outline these challenges and explore solutions. Furthermore, we consider the potential future of LS care and the related treatments and interventions which are the current focus of research.Keywords: genetic counselling, Lynch syndrome, mainstreaming
