name	description	evidence
MLH1 Mutation	Caused by a mutation in the MLH1 gene, which is involved in DNA mismatch repair.	TRUNCATED
MSH2 Mutation	Caused by a mutation in the MSH2 gene, which is involved in DNA mismatch repair.	TRUNCATED
MSH6 Mutation	Caused by a mutation in the MSH6 gene, which is involved in DNA mismatch repair.	TRUNCATED
PMS2 Mutation	Caused by a mutation in the PMS2 gene, which is involved in DNA mismatch repair.	TRUNCATED
EPCAM Deletion	Caused by a deletion in the EPCAM gene, which can lead to silencing of the MSH2 gene.	TRUNCATED

0

population

General Population

percentage

0.03-0.05

evidence

reference	supports	snippet	explanation
PMID:35177335	WRONG_STATEMENT	Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, with an estimated prevalence of 2% to 3% of CRC.	The literature suggests the prevalence of Lynch syndrome in colorectal cancer patients is around 2% to 3%, but not in the general population.
PMID:35177335	WRONG_STATEMENT	The overall pooled yield of LS screening was 2.2% based on all methods of detection.	The prevalence mentioned is for LS screening in CRC patients, not the general population.
PMID:37879520	WRONG_STATEMENT	We describe the experience of Lynch syndrome (LS) diagnosis in the province of Manitoba, Canada, over the past 20 years.	The study focuses on the diagnosis in a specific region and does not establish a general population prevalence of 0.03-0.05%.
PMID:25430799	WRONG_STATEMENT	Diagnosis of Lynch syndrome (LS) may be complex. Knowledge of mutation spectrum and founder mutations in specific populations facilitates the diagnostic process.	The study is about diagnosis in the Israeli population and does not support the claim of a 0.03-0.05% general prevalence.

0

phase

Onset

evidence

reference	supports	snippet	explanation
PMID:33506248	NO_EVIDENCE	Lynch Syndrome is one of the most common hereditary cancer syndromes, arising from DNA mismatch repair. Lynch Syndrome carriers are at increased lifetime risk of developing certain cancers, such as colorectal and endometrial. This increased risk can result in adverse psychological outcomes.	The provided literature discusses the risks and psychological impacts of Lynch Syndrome but does not provide evidence related to the specific progression or onset phase details of the syndrome.
PMID:33433757	NO_EVIDENCE	Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms.	This reference speaks about the genetic causation and predispositions associated with Lynch Syndrome but does not discuss the progression phases.
PMID:25673086	NO_EVIDENCE	Lynch syndrome, which is now recognized as the most common hereditary colorectal cancer condition, is characterized by the predisposition to a spectrum of cancers, primarily colorectal cancer and endometrial cancer.	This snippet mentions the types of cancers associated with Lynch Syndrome but does not provide information on the progression phase or onset details of the condition.

1

age_range

20-50

evidence

reference	supports	snippet	explanation
PMID:34911717	PARTIAL	Disease-predisposing alterations in MLH1 and MSH2 were overrepresented in the age 15-39 cohort compared with patients diagnosed over age 40.	The study shows that a significant portion of the disease progression occurs in individuals under 40, but it does not specifically confirm the age range of 20-50.
PMID:33433757	SUPPORT	Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms.	This literature highlights that mutations related to Lynch syndrome cause progression to cancer in a broad age range. While not specifying 20-50 years directly, it supports progression within and beyond this range.
PMID:36942845	NO_EVIDENCE	Lynch syndrome: toward an increasingly complex picture. The case of PMS2.	The title suggests an exploration of complexity related to PMS2 but does not provide specific evidence on the age range of progression.
PMID:24857057	NO_EVIDENCE	This brief overview highlights the gene-specific and site-specific cancer penetrance and management options for those with Lynch syndrome.	No specific mention of progression within the age range 20-50 years.
PMID:25489705	NO_EVIDENCE	Mismatch repair gene deficiency and genetic anticipation in Lynch syndrome: myth or reality?	The abstract does not provide specific insights into the age range for progression.
PMID:23471748	NO_EVIDENCE	The report by Aldred Scott Warthin in 1913 of a cancer family history and expanded on by Henry T. Lynch demonstrated one of the most enduring traits observed in patients with Lynch syndrome.	The literature review does not provide specific evidence on the age range 20-50 years.
PMID:33746161	SUPPORT	The median ages at the first cancer and the genetic diagnosis were 47 (34-71) and 62 (38-84) years old, respectively.	The data indicates cancer progression occurs within the stated age range, hence supporting this age range partially.
PMID:32039553	NO_EVIDENCE	Cancer surveillance is important...adherence to guidelines.	No specific mention of progression within the age range 20-50 years.

0

name

DNA Mismatch Repair Deficiency

description

Mutations in mismatch repair genes lead to an accumulation of DNA replication errors.

evidence

reference	supports	snippet	explanation
PMID:19466295	SUPPORT	Lynch syndrome represents 1-7% of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes.	This reference confirms that Lynch Syndrome involves mutations in mismatch repair genes.
PMID:29233924	SUPPORT	Many mutations first arise as DNA replication errors. These errors subsequently evade correction by cellular DNA repair, for example, by the well-known DNA mismatch repair (MMR) mechanism.	This supports the notion that DNA mismatch repair is crucial in correcting DNA replication errors, and its deficiency leads to the accumulation of these errors.
PMID:8543151	SUPPORT	DNA mismatch-repair systems exist that repair mispaired bases formed during DNA replication... Genetic defects in mismatch-repair genes play an important role in common cancer-susceptibility syndromes and sporadic cancers.	Supports the fact that defects in DNA mismatch repair are linked with cancer susceptibility, reinforcing the role of DNA repair in Lynch Syndrome.
PMID:34919656	SUPPORT	Lynch syndrome (LS, OMIM #120435) is caused by an inherited heterozygous defect in any of the four core DNA mismatch repair (MMR) genes MSH2, MSH6, MLH1 or PMS2...	Clear evidence linking inherited defects in mismatch repair genes to Lynch Syndrome.
PMID:24443998	SUPPORT	Inherited defects in the DNA mismatch repair (MMR) system, MLH1, MSH2, MSH6, and PMS2 genes, underlie Lynch syndrome, one of the most prevalent cancer syndromes in man.	Validates that Lynch Syndrome is underpinned by mutations in specific mismatch repair genes.

biological_processes

• DNA Repair

1

name

Microsatellite Instability

description

Defective mismatch repair causes variations in the length of repetitive DNA sequences called microsatellites.

evidence

reference	supports	snippet	explanation
PMID:25701956	SUPPORT	Deficient DNA mismatch repair (MMR) results in a strong mutator phenotype known as microsatellite instability (MSI), which is a hallmark of Lynch syndrome-associated cancers.	The snippet confirms that defective mismatch repair causes microsatellite instability, supporting the statement.
PMID:35315099	SUPPORT	LS tumours are characterised by unique pathogenesis, ultimately resulting in hypermutation, microsatellite instability and high immunogenicity that has significant implications for cancer risk, clinical presentation, treatment and surveillance.	The statement is supported by the evidence that Lynch Syndrome leads to microsatellite instability due to defective mismatch repair.
PMID:31273487	SUPPORT	Lynch syndrome is a state of mismatch repair deficiency due to a monoallelic abnormality of any mismatch repair genes. The phenotype indicating the mismatch repair deficiency can be frequently shown as a microsatellite instability in tumors.	This reference supports the statement by linking mismatch repair deficiency and microsatellite instability in Lynch Syndrome.
PMID:38466935	SUPPORT	Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes, which lead to high microsatellite instability and frameshift mutations at coding mononucleotide repeats in the genome.	The snippet supports the statement by describing how defective mismatch repair in Lynch syndrome leads to microsatellite instability.

2

name

Accelerated Tumor Development

description

The accumulation of mutations in key genes leads to an increased risk of developing certain cancers at an earlier age.

evidence

reference	supports	snippet	explanation
PMID:33433757	SUPPORT	Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms.	This supports the mechanism that Lynch Syndrome involves accumulation of mutations in key genes (MMR genes) leading to an increased risk of cancer.
PMID:37478804	SUPPORT	Lynch Syndrome (LS) is one of the most common hereditary cancer syndromes, and is caused by mutations in one of the four DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6 and PMS2.	This further supports the fact that accumulation of mutations in key genes (MMR genes) in Lynch Syndrome contributes to an increased risk of developing certain cancers.
PMID:23604856	SUPPORT	Lynch Syndrome, or hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome caused by inactivating mutations in DNA mismatch repair genes.	This supports the idea that the mechanism of Lynch Syndrome involves the accumulation of mutations in key genes leading to cancer.

0

category

Gastrointestinal

name

Colorectal Cancer

frequency

VERY_FREQUENT

diagnostic

True

sequelae

Metastatic Disease Bowel Obstruction

evidence

reference	supports	snippet	explanation
PMID:30134129	SUPPORT	Lynch Syndrome-Associated Colorectal Cancer.	This reference directly discusses colorectal cancer associated with Lynch syndrome, supporting the statement about its phenotype and diagnostic category as gastrointestinal with high frequency.
PMID:37088804	PARTIAL	Some patients with Lynch syndrome (LS) have extreme phenotypes, i.e. cancer before the recommended screening age, or cancer for which there are no screening guidelines.	While this study mentions patients with Lynch syndrome having early-onset cancer, it does not specify whether it includes colorectal cancer or not. It partially supports the statement on phenotypes.
PMID:16136388	SUPPORT	The major aim of surveillance in Lynch syndrome is to diagnose malignant or premalignant lesions at the asymptomatic stage by regular checkups, particularly in the large bowel.	Supports the high frequency of colorectal cancer diagnosis in Lynch syndrome as a major phenotype.
PMID:29071502	SUPPORT	Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer...	Affirms that Lynch syndrome frequently predisposes to colorectal cancer, supporting a high-frequency diagnostic.
PMID:23681793	SUPPORT	Lynch syndrome (LS), one of the most frequent forms of hereditary colorectal cancer (CRC)...	This supports the statement mentioning Lynch syndrome as frequently associated with hereditary colorectal cancer.
PMID:34798988	SUPPORT	Lynch syndrome (LS) is a common form of inherited cancer susceptibility, which predisposes to colorectal cancer (CRC)...	This reference supports the common occurrence of colorectal cancer in individuals with Lynch syndrome.
PMID:36031446	SUPPORT	Lynch syndrome is associated with the most common form of heritable bowel cancer.	This supports that colorectal cancer is a common gastrointestinal phenotype in Lynch syndrome.
PMID:26974895	SUPPORT	Lynch syndrome accounts for roughly 1 of every 35 patients with colorectal carcinoma, making it the most common hereditary form of colorectal carcinoma.	This directly supports the statement that colorectal cancer is a frequent diagnostic and phenotype in Lynch syndrome.
PMID:21325953	SUPPORT	Individuals with Lynch syndrome have an increased risk for colorectal cancer...	Supports the high frequency of colorectal cancer in individuals with Lynch syndrome.
PMID:35306248	SUPPORT	Lynch Syndrome carriers are at increased lifetime risk of developing certain cancers, such as colorectal and endometrial.	Supports the statement of colorectal cancer phenotype in Lynch syndrome as it emphasizes colorectal cancer risk.

1

category

Gynecologic

name

Endometrial Cancer

frequency

VERY_FREQUENT

evidence

reference	supports	snippet	explanation
PMID:28376523	SUPPORT	The clinical characteristics of Lynch-associated endometrial cancer and screening and risk-reducing strategies also are described.	The article discusses Lynch syndrome and its association with endometrial cancer, supporting the statement.
PMID:23681793	SUPPORT	Carriers of MMR defects have a strongly increased risk of developing CRC and endometrial cancer.	The article states that Lynch syndrome carriers have a strongly increased risk of developing endometrial cancer.
PMID:29071502	SUPPORT	Lynch syndrome is the hereditary disorder that most frequently predisposes to colorectal cancer as well as predisposing to a number of extracolonic cancers, most prominently endometrial cancer.	The review confirms that Lynch syndrome prominently predisposes individuals to endometrial cancer.
PMID:37728516	SUPPORT	Lynch syndrome (LS) markedly increases risks of colorectal and endometrial cancers.	This reference further supports the statement that Lynch syndrome is strongly associated with endometrial cancer.

2

category

Gastrointestinal

name

Stomach Cancer

frequency

FREQUENT

evidence

reference	supports	snippet	explanation
PMID:31319185	SUPPORT	Lynch syndrome is the most common inherited cause of gastrointestinal cancer and increases risk for a variety of malignancies, including gastric cancer.	The reference supports the increased frequency of stomach (gastric) cancer as a phenotype of Lynch Syndrome.
PMID:27546846	PARTIAL	Approximately 5% arise from germline mutations in genes associated with cancer predisposition.	While this provides general context about hereditary gastrointestinal cancers, it does not specify Lynch Syndrome or stomach cancer.

3

category

Genitourinary

name

Urinary Tract Cancer

frequency

OCCASIONAL

evidence

reference	supports	snippet	explanation
PMID:31615790	SUPPORT	Lynch syndrome confers markedly increased risks of various malignancies, including urinary tract cancers (UTC; renal pelvis, ureter, bladder, and possibly kidney cancers).	The study indicates that Lynch syndrome is associated with an increased risk of urinary tract cancers, supporting the statement.
PMID:23700068	SUPPORT	Urinary tract cancers (UTC) have in many studies been reported increased in LS and it has been discussed among researchers and clinicians whether or not screening for urological tumours should be included in the surveillance programme.	The review discusses the increased risk of urinary tract cancers in Lynch syndrome, supporting the statement.

4

category

Dermatologic

name

Sebaceous Adenomas

frequency

OCCASIONAL

evidence

reference	supports	snippet	explanation
PMID:25427047	PARTIAL	Muir-Torre syndrome (MTS) is a rare autosomal-dominant genodermatosis characterized by sebaceous neoplasms and one or more visceral malignancies. Sebaceous tumors include sebaceous adenoma and carcinoma, which may be solitary or multiple.	Sebaceous adenomas are part of Muir-Torre syndrome, a phenotypic subtype of Lynch Syndrome. However, the literature does not specify the frequency as 'occasional.'
PMID:36418753	PARTIAL	The main skin lesions were: Sebaceous adenomas (43%), sebaceous carcinomas (27%), keratoacanthomas (16%), sebaceomas (13%), squamous cell carcinomas (23%), and basal cell carcinomas (10%).	Sebaceous adenomas are significant dermatologic manifestations of Lynch Syndrome, but the literature suggests they are more frequent than 'occasional'.

name	evidence	notes
Microsatellite Instability Testing	TRUNCATED	High microsatellite instability in tumors
Immunohistochemistry	TRUNCATED	Absent mismatch repair proteins in tumors

0

name

MLH1

evidence

reference	supports	snippet	explanation
PMID:28038733	SUPPORT	Lynch syndrome is due to germline mutations in mismatch repair genes: MLH1, MSH2, MSH6 and PMS2.	The reference directly indicates that Lynch syndrome is caused by germline mutations in the MLH1 gene among others.
PMID:37142200	SUPPORT	Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2.	The statement is directly supported as this reference confirms the association of Lynch syndrome with germline mutations in the MLH1 gene.
PMID:33433757	SUPPORT	Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms.	The explanation here reinforces the link between Lynch Syndrome and germline mutations in the MLH1 gene.
PMID:26886015	SUPPORT	Constitutional epimutation of the DNA mismatch repair gene, MLH1, represents a minor cause of Lynch syndrome.	While the term 'epimutation' is used, it is within the context of the DNA mismatch repair gene MLH1 being a cause of Lynch syndrome.
PMID:37142200	SUPPORT	Previous studies showed that MLH1, MSH2, MSH6, and PMS2 mutation in LS were associated with an elevated risk of colorectal, gastric, endometria, ovarian, and other cancers among family members.	The germline mutation in the MLH1 gene is explicitly stated to be associated with Lynch syndrome.

association

Germline Mutation

1

name

MSH2

evidence

reference	supports	snippet	explanation
PMID:29345684	PARTIAL	Our data demonstrate that two LS genes, MSH6 and PMS2, are associated with an increased risk for breast cancer...	While the MSH2 gene is mentioned, the research did not find a statistically significant association between MSH2 and breast cancer risk.
PMID:33433757	SUPPORT	Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2...	This supports that Lynch syndrome can be caused by germline mutations in MSH2 among other genes.
PMID:16500024	SUPPORT	Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary syndrome caused by mutations or epigenetic silencing in DNA mismatch repair genes, MLH1, MSH2, MSH6, PMS2...	This provides evidence that MSH2 mutations are one of the causes of Lynch syndrome.
PMID:33357406	SUPPORT	In Lynch syndrome (LS), nearly 90% of clinically observed missense variants are deemed 'variants of uncertain significance' (VUS)...we performed a massively parallel screen in human cells to identify loss-of-function missense variants in the key DNA mismatch repair factor MSH2.	Directly supports the assertion that germline mutations in MSH2 are associated with Lynch syndrome.
PMID:25430799	SUPPORT	Sixty-seven (59%) families had mutations in MSH2...	This study reports a significant proportion of Lynch syndrome families with mutations in MSH2.
PMID:36942845	SUPPORT	Lynch syndrome is caused primarily by germline mutations in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2).	Confirms the association of MSH2 germline mutations with Lynch syndrome.

association

Germline Mutation

2

name

MSH6

evidence

reference	supports	snippet	explanation
PMID:20028993	SUPPORT	Germline mutations in MSH6 account for 10%-20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations.	The study explicitly states that germline mutations in MSH6 are associated with Lynch Syndrome cancers.
PMID:33433757	SUPPORT	Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2...	The abstract confirms that Lynch Syndrome is associated with germline mutations in the MSH6 gene, among others.
PMID:28038733	SUPPORT	Lynch syndrome is due to germline mutations in mismatch repair genes: MLH1, MSH2, MSH6 and PMS2.	The study identifies germline mutations in MSH6 as a cause of Lynch Syndrome.
PMID:33516942	SUPPORT	A MSH6 3'UTR variant (c.*23_26dup) was found in 13 unrelated families consulted for Lynch/Muir-Torre Syndrome.	The study highlights that a specific variant of MSH6 is associated with families affected by Lynch Syndrome.
PMID:25430799	SUPPORT	Sixty-seven (59%) families had mutations in MSH2, 20 (18%) in MSH6, 19 (17%) in MLH1 and 7 (6%) in PMS2.	The study identifies families with Lynch Syndrome who have mutations in the MSH6 gene.
PMID:33094597	SUPPORT	Genetic analysis turned out positive for biallelic MSH6 mutations in the two girls, leading to CMMRD syndrome diagnosis. Both parents and two out of three alive siblings were diagnosed with Lynch syndrome.	This informs about Lynch Syndrome diagnosis in individuals with MSH6 mutations.

association

Germline Mutation

3

name

PMS2

evidence

reference	supports	snippet	explanation
PMID:18602922	SUPPORT	PMS2 mutations contribute significantly to Lynch syndrome, but the penetrance for monoallelic mutation carriers appears to be lower than that for the other mismatch repair genes.	This study confirms that germline mutations in PMS2 are associated with Lynch syndrome.
PMID:33433757	SUPPORT	Lynch syndrome (LS) is an autosomal dominant inherited disease caused by germline mutations in DNA mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, and PMS2, which predisposes patients to various malignant neoplasms.	This study identifies germline mutations in PMS2 as one of the genetic causes of Lynch syndrome.
PMID:24027009	SUPPORT	Lynch syndrome (LS) is a common cancer predisposition caused by an inactivating mutation in one of four DNA mismatch repair (MMR) genes. Frequently a variant of uncertain significance (VUS), rather than an obviously pathogenic mutation, is identified in one of these genes. The inability to define pathogenicity of such variants precludes targeted healthcare.	The study discusses analyzing VUS in the MMR gene PMS2 for functional activity, indicating the association of PMS2 germline mutations with Lynch syndrome.
PMID:37072247	SUPPORT	As a result of our analysis, we managed to identify a mutation in the PMS2 gene in one patient's breast tumor tissue. The presence of this mutation indicates that the resulting cancer may be a consequence of LS.	This study identifies a mutation of the PMS2 gene associated with Lynch syndrome, supporting the genetic association.
PMID:25430799	SUPPORT	We identified 54 different mutations; 13 of them are novel... Seven founder mutations were detected in 61/113 (54%) families... Gene distribution in the Israeli population is unique...7 (6%) in PMS2.	PMS2 is one of the genes where germline mutations have been identified as causing Lynch syndrome.

association

Germline Mutation

4

name

EPCAM

evidence

reference	supports	snippet	explanation
PMID:23411950	SUPPORT	Germline mutations of 4 MMR genes, e.g., MLH1, MSH2, MSH6 and PMS2, had been identified as the cause of this disease, however, a novel mechanism, epigenetic inactivation of MSH2 gene due to hypermethylation of promotor region by the deletion of 3'part of epithelial cell adhesion molecule(EPCAM) gene which is located upstream of the MSH2 gene, has been reported in recent years.	None
PMID:30461124	SUPPORT	Monoallelic deletions of the 3' end of EPCAM that silence the downstream gene, MSH2, cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair.	None
PMID:37088804	SUPPORT	Four EO cases stood out: two with POLE/POLD1 variants in the key exonuclease domain, one with a BMPR1A duplication and one with an EPCAM deletion.	EPCAM deletion is mentioned as one of the variants related to Lynch Syndrome.

association

Germline Mutation

0

name

Not Applicable

evidence

reference	supports	snippet	explanation
PMID:29345160	REFUTE	Environmental factors that play a role in the urothelial carcinogenesis have been well characterized. Current research is continuously exploring potential heritable forms of bladder cancer. Lynch syndrome is a well-known inheritable disease that increases the risk for a variety of cancers, including urothelial carcinomas.	Lynch syndrome is described as an inherited disease, implying a genetic rather than environmental origin.
PMID:31296810	REFUTE	Lynch syndrome is caused by germline pathogenic variants in any of 4 DNA mismatch repair(MMR)genes MLH1, MSH2, MSH6 or PMS2 and rarely in the non-MMR gene EPCAM, in which deletion of its last exon induce epigenetic silencing of MSH2.	This indicates that Lynch syndrome is caused by genetic mutations, not by environmental factors.

notes

Lynch syndrome is primarily caused by inherited genetic mutations.

0

name

Increased Cancer Surveillance

description

Regular colonoscopies, endometrial biopsies, and other screening tests to detect cancers early.

evidence

reference	supports	snippet	explanation
PMID:23176623	SUPPORT	Some periodic screening strategies, such as colonoscopy, reduce the incidence and mortality of Lynch syndrome.	Regular colonoscopies are highlighted as a beneficial screening strategy for Lynch Syndrome.
PMID:31629885	SUPPORT	...offering the FDRs with Lynch syndrome biennial colonoscopy surveillance was cost-effective...	The study emphasizes the importance of regular colonoscopy surveillance for those with Lynch syndrome.
PMID:34698909	SUPPORT	Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer and is associated with an increased lifetime risk of gastric and duodenal cancers of 8-16% and 7%, respectively; therefore, we aim to describe an esophagogastroduodenoscopy (EGD) surveillance program...	Endoscopies like EGD are implemented for cancer surveillance in LS patients, corroborating the need for ongoing screening tests.
PMID:32875945	SUPPORT	Universal tumor screening is a strategy to identify high-risk individuals by testing all CRC tumors for molecular features suggestive of Lynch Syndrome.	Universal tumor screening further illustrates the importance of regular and early cancer detection methods for Lynch Syndrome patients.
PMID:27241104	SUPPORT	This review discusses the rationales and relative merits of current Lynch syndrome screening tests for endometrial and ovarian cancers...	Endometrial biopsies and other screening tests are discussed in the context of Lynch Syndrome, supporting the statement.

1

name

Prophylactic Surgery

description

Preventive removal of the colon, uterus, or ovaries may be considered in some cases.

evidence

reference	supports	snippet	explanation
PMID:21287222	SUPPORT	Patients who are gene mutation carriers should receive counseling about colectomy, and if women, prophylactic hysterectomy and bilateral oophorectomy.	The literature mentions counseling carriers about colectomy and prophylactic hysterectomy with bilateral oophorectomy, supporting that preventive removal of the colon, uterus, or ovaries may be considered.
PMID:24495259	SUPPORT	Prophylactic hysterectomy with bilateral salpingo-oophorectomy is being increasingly undertaken in patients with Lynch syndrome (LS).	The literature indicates that prophylactic hysterectomy with bilateral salpingo-oophorectomy is a preventive measure undertaken in Lynch syndrome patients.
PMID:31554630	SUPPORT	for women with Lynch syndrome, the risks for gynecologic cancers pose an equal or greater risk than colorectal cancer.	The literature outlines the significant risk of gynecologic cancers in women with Lynch syndrome, supporting the consideration of prophylactic surgery.
PMID:27241104	SUPPORT	This review discusses the rationales and relative merits of current Lynch syndrome screening tests for endometrial and ovarian cancers.	The discussion of screening tests implies the consideration of proactive measures, including prophylactic surgery, in managing the elevated cancer risks in Lynch syndrome.

2

name

Chemoprevention

description

Aspirin or other NSAIDs may reduce the risk of colorectal cancer in Lynch syndrome patients.

evidence

reference	supports	snippet	explanation
PMID:35328014	SUPPORT	Nonsteroidal anti-inflammatory drugs and, in particular, aspirin use, has been associated with reduced CRC risk in several studies...	This study affirms that aspirin and other NSAIDs have been linked to a reduced risk of colorectal cancer in Lynch syndrome patients.
PMID:11854387	PARTIAL	Numerous experimental, epidemiologic, and clinical studies suggest that nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the highly selective cyclooxygenase (COX)-2 inhibitors, have promise as anticancer agents...	The study indicates a potential for NSAIDs in cancer prevention, including colorectal cancer, but notes that unresolved questions about safety and efficacy limit clinical application.
PMID:36202092	SUPPORT	...multiple pharmacological, clinical, and epidemiologic studies suggest that aspirin can prevent certain cancers...	This study supports the role of aspirin in cancer prevention, including colorectal cancer, though mentions variable effects depending on the tissue and disease context.
PMID:34798982	SUPPORT	Secondary prevention of colorectal neoplasia with chemoprevention is a long-studied area of research and clinical use in patients with the 2 most common hereditary colorectal cancer syndromes including Lynch syndrome...	This study notes the history and research supporting chemoprevention, including with NSAIDs, for hereditary colorectal cancer syndromes like Lynch syndrome.

3

name

Targeted Therapies

description

Immunotherapies like checkpoint inhibitors may be effective for treating some Lynch syndrome-related cancers.

evidence

reference	supports	snippet	explanation
PMID:37625240	SUPPORT	PD-1 inhibitors are highly effective for dMMR and MSI-H LS CRCs, but not for pMMR or MSS LS CRCs or mucinous/signet-ring cell CRC.	This study demonstrates the efficacy of PD-1 inhibitors, a type of immune checkpoint inhibitor, for treating Lynch syndrome (LS) patients with colorectal cancers characterized by deficient mismatch repair (dMMR) or high microsatellite instability (MSI-H).
PMID:34224739	SUPPORT	We identified 4 shared FSP neoantigens ... Using VCMsh2 mice, which have a conditional knockout of Msh2 in the intestinal tract and develop intestinal cancer, we showed vaccination with a combination of only 4 FSPs significantly increased FSP-specific adaptive immunity, reduced intestinal tumor burden, and prolonged overall survival.	This study indicates that immunotherapies, specifically FSP neoantigen vaccines, can be effective in reducing the tumor burden and improving survival in Lynch syndrome mouse models.
PMID:30027543	SUPPORT	Immunotherapies are an active field of research for MSI cancers and their potential use for cancer therapy for both sporadic and LS MSI cancers is discussed.	This reference discusses ongoing research into immunotherapies for MSI cancers, including those associated with Lynch syndrome.
PMID:37845474	PARTIAL	Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB).	While ICB is effective for treating dMMR tumors in Lynch syndrome patients, it does not eliminate the risk of new neoplasia development, highlighting the need for continued surveillance.

Hereditary Cancer Syndrome Colorectal Cancer Predisposition