{"entity":{"id":"lynch-associated-colorectal-cancer","kind":"cancer","name":"Lynch syndrome-associated colorectal cancer","aka":["Lynch syndrome-associated colorectal cancer (inherited mismatch repair variant; about 1 to 4 percent of colon cancers)","Lynch syndrome (hereditary dMMR, ~3%)","Hereditary non-polyposis colorectal cancer","HNPCC","Lynch syndrome bowel cancer","Mismatch repair germline colorectal cancer"],"tldr":"Lynch syndrome-associated bowel cancer is bowel cancer in someone born with a fault in one of the genes that proofread DNA copying errors. The tumours tend to arise younger and on the right side, they carry the mismatch repair defect that makes immunotherapy work, and the diagnosis changes the care of the whole family as well as the care of the patient.","summary":"What it is. Lynch syndrome is an inherited condition caused by a germline variant in one of the mismatch repair genes MLH1, MSH2, MSH6 or PMS2, or by a deletion in EPCAM that silences MSH2. The proofreading system that corrects copying errors in repetitive DNA fails, the tumour accumulates insertions and deletions at those repeats, and the result is a mismatch repair-deficient, microsatellite-unstable cancer. The World Health Organization lists it among the genetic tumour syndromes of the digestive system, and it is the commonest inherited cause of bowel cancer (Nagtegaal 2020).\n\nHow it differs from its parent. Two things distinguish it from mismatch repair-deficient bowel cancer in general. The defect is inherited rather than acquired, so relatives are at risk and cascade testing follows the diagnosis; and the cancers behave differently by gene. In the Prospective Lynch Syndrome Database, 1,942 carriers without previous cancer were followed for 13,782 observation years under colonoscopic surveillance: cancers appeared from age 25 in MLH1 and MSH2 carriers but only from about 40 in MSH6 and PMS2 carriers, and the cumulative incidence of colorectal cancer by age 70 was 46 percent for MLH1, 35 percent for MSH2, 20 percent for MSH6 and 10 percent for PMS2. Endometrial cancer reached 34, 51, 49 and 24 percent by the same age. Colorectal cancer occurred despite surveillance but killed few people: ten-year crude survival was 91 percent when the first cancer was colorectal (Moller 2017). Sporadic mismatch repair-deficient cancers, by contrast, usually arise through methylation of the MLH1 promoter in older people through the serrated pathway, and have no implication for relatives.\n\nHow common it is. Modelling of 5,744 families put the population prevalence of a mismatch repair variant at 1 in 279 (Win 2017); Cancer Research UK records that hereditary non-polyposis colorectal cancer accounts for 1 to 4 percent of colon cancers, and that around 9 in 10 men and 7 in 10 women with it develop bowel cancer by age 70.\n\nHow it is treated. The cancer itself is treated as colorectal cancer of the same stage and molecular profile, which in practice means the mismatch repair-deficient pathways: checkpoint inhibitors in metastatic disease, and the neoadjuvant and adjuvant immunotherapy strategies the parent record carries. What is specific to Lynch syndrome is everything around the tumour. NICE NG151 (1.1.1) says to consider daily aspirin for more than two years to reduce colorectal cancer risk, on the strength of CAPP2, in which 600 mg daily cut colorectal cancer over ten years (hazard ratio 0.65 by intention to treat, 0.56 in those who completed two years) (Burn 2020). Colonoscopic surveillance, the extent of surgery when a cancer is found, gynaecological risk-reducing surgery and cascade testing of relatives follow the British Society of Gastroenterology, ACPGBI and UK Cancer Genetics Group guidelines (Monahan 2020).","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/Lynch_syndrome","links":[{"label":"Win, Cancer Epidemiol Biomarkers Prev 2017: prevalence and penetrance of major genes and polygenes for colorectal cancer (5,744 families)","url":"https://doi.org/10.1158/1055-9965.epi-16-0693"},{"label":"Moller, Gut 2017: cancer incidence and survival in Lynch syndrome under surveillance, the Prospective Lynch Syndrome Database (1,942 carriers)","url":"https://doi.org/10.1136/gutjnl-2015-309675"},{"label":"Burn, Lancet 2020: CAPP2, cancer prevention with aspirin in Lynch syndrome, 10-year follow-up (861 patients randomised)","url":"https://doi.org/10.1016/s0140-6736(20)30366-4"},{"label":"Monahan, Gut 2020: BSG, ACPGBI and UKCGG guidelines for the management of hereditary colorectal cancer","url":"https://doi.org/10.1136/gutjnl-2019-319915"},{"label":"NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"},{"label":"CRUK: bowel cancer risk factors (professional)","url":"https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bowel-cancer/risk-factors"},{"label":"Nagtegaal, Histopathology 2020: the 2019 WHO classification of tumours of the digestive system","url":"https://doi.org/10.1111/his.13975"}],"tags":["gi","colorectal","subtype-page"],"related":["colorectal","msi-high-colorectal","fap-associated-colorectal-cancer","early-onset-colorectal","endometrial","colon-cancer","rectal-cancer"],"cancers":[],"sections":[],"technologies":["msi-mmr-testing","germline-testing","histopathology-ihc","aspirin-cancer-prevention","chemoprevention"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lynch-syndrome","msi","mlh1-promoter-methylation","germline-vs-somatic","colonoscopy-surveillance-intervals","serrated-pathway"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"gastrointestinal","burden":"About 1 in 279 people carry a mismatch repair variant (MLH1 1 in 1,946, MSH2 1 in 2,841, MSH6 1 in 758, PMS2 1 in 714), and hereditary non-polyposis colorectal cancer accounts for 1 to 4 percent of colon cancers (Win 2017; Cancer Research UK).","subtypes":["MLH1-associated Lynch syndrome (colorectal cancer in 46 percent by age 70)","MSH2-associated Lynch syndrome, including EPCAM deletions (colorectal cancer in 35 percent by age 70)","MSH6-associated Lynch syndrome (colorectal cancer in 20 percent by age 70; later onset)","PMS2-associated Lynch syndrome (colorectal cancer in 10 percent by age 70; later onset)","Constitutional mismatch repair deficiency (biallelic variants; childhood tumours)"],"biomarkers":["Mismatch repair protein loss on immunohistochemistry, or microsatellite instability, on every colorectal cancer at diagnosis","MLH1 promoter methylation and BRAF V600E testing to separate sporadic from inherited mismatch repair loss","Germline testing of MLH1, MSH2, MSH6, PMS2 and EPCAM to confirm the diagnosis and to test relatives"],"standardOfCare":[{"setting":"Finding the syndrome","approach":"Mismatch repair immunohistochemistry or microsatellite instability testing on every colorectal cancer; MLH1 promoter methylation testing where MLH1 is lost, because most of those cancers are sporadic; germline testing when methylation is absent, then cascade testing of relatives.","refs":["msi-mmr-testing","histopathology-ihc","germline-testing","lynch-syndrome","mlh1-promoter-methylation"],"guideline":{"version":"NICE NG151: colorectal cancer (published January 2020, last updated December 2021, last reviewed April 2026)","url":"https://www.nice.org.uk/guidance/ng151"}},{"setting":"Risk reduction in carriers","approach":"Consider daily aspirin for more than two years (NICE NG151 1.1.1, from CAPP2); colonoscopic surveillance at intervals set by gene and age; discussion of the extent of colectomy when a cancer is found; gynaecological risk-reducing surgery after childbearing for women.","refs":["aspirin-cancer-prevention","colonoscopy","colonoscopy-surveillance-intervals","colectomy","chemoprevention"],"guideline":{"version":"NICE NG151: colorectal cancer (published January 2020, last updated December 2021, last reviewed April 2026)","url":"https://www.nice.org.uk/guidance/ng151"}}],"stateOfArt":[],"history":[],"pipeline":[],"openProblems":[],"parent":"colorectal"},"route":"/cancers/lynch-associated-colorectal-cancer/","neighbours":{"cancer":[{"id":"colon-cancer","kind":"cancer","name":"Colon cancer (adenocarcinoma of the colon)","route":"/cancers/colon-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"early-onset-colorectal","kind":"cancer","name":"Early-onset colorectal cancer (under 50)","route":"/cancers/early-onset-colorectal/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"fap-associated-colorectal-cancer","kind":"cancer","name":"Familial adenomatous polyposis-associated colorectal cancer","route":"/cancers/fap-associated-colorectal-cancer/"},{"id":"msi-high-colorectal","kind":"cancer","name":"Mismatch-repair deficient (MSI-high) colorectal cancer","route":"/cancers/msi-high-colorectal/"},{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"}],"technology":[{"id":"aspirin-cancer-prevention","kind":"technology","name":"Aspirin for cancer prevention and adjuvant therapy","route":"/technologies/aspirin-cancer-prevention/"},{"id":"chemoprevention","kind":"technology","name":"Chemoprevention & risk-reducing surgery","route":"/technologies/chemoprevention/"},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"msi-mmr-testing","kind":"technology","name":"MSI and mismatch-repair testing","route":"/technologies/msi-mmr-testing/"}],"term":[{"id":"colectomy","kind":"term","name":"Colectomy","route":"/terms/colectomy/"},{"id":"colonoscopy","kind":"term","name":"Colonoscopy","route":"/terms/colonoscopy/"},{"id":"germline-vs-somatic","kind":"term","name":"Germline vs somatic mutations","route":"/terms/germline-vs-somatic/"},{"id":"lynch-syndrome","kind":"term","name":"Lynch syndrome","route":"/terms/lynch-syndrome/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"mlh1-promoter-methylation","kind":"term","name":"MLH1 promoter methylation (sporadic versus Lynch mismatch repair loss)","route":"/terms/mlh1-promoter-methylation/"},{"id":"serrated-pathway","kind":"term","name":"Serrated pathway","route":"/terms/serrated-pathway/"},{"id":"colonoscopy-surveillance-intervals","kind":"term","name":"Surveillance intervals after polypectomy","route":"/terms/colonoscopy-surveillance-intervals/"}]}}