Materiały źródłowe

• #1 Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis – UpToDate

  https://www.uptodate.com/contents/lynch-syndrome-hereditary-nonpolyposis-colorectal-cancer-clinical-manifestations-and-diagnosis

  Lynch syndrome is the most common cause of inherited colorectal cancer (CRC). It is characterized by a significantly increased risk for CRC and endometrial cancer as well as a risk of several other malignancies. This topic will review the genetic basis, clinical manifestations, and diagnosis of Lynch syndrome. […] Lynch syndrome refers to patients and families with a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) or the EPCAM gene. […] Lynch syndrome is the most common inherited CRC susceptibility syndrome and accounts for approximately 3 percent of newly diagnosed cases of CRC and 2 to 3 percent of endometrial cancer. […] Lynch syndrome is an autosomal dominant disorder that is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes or loss of expression of MSH2 due to deletion in the EPCAM gene.

• #2 Lynch Syndrome Testing

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/lynch-syndrome-testing/

  Lynch Syndrome Testing – CAM 169 […] Lynch syndrome (LS) (also known as hereditary non-polyposis colorectal cancer; HNPCC) is the most common form of hereditary colorectal (CRC) and endometrial cancers (EMC), resulting from an autosomal dominant inactivation of any of four mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) leading to microsatellite instability (MSI) (Rumilla et al., 2011) and associated with an increased risk of colorectal, endometrial, stomach, small bowel, and ovarian cancers (Hunter et al., 2015; Lynch et al., 2009; Moreira et al., 2012). […] For guidance concerning Tumor Mutational Burden Testing (TMB) and/or Microsatellite instability (MSI) analysis please refer to CAM 342-Microsatellite Instability and Tumor Mutational Burden Testing policy. […] On Oct. 27, 2017 the FDA approved VENTANA MMR IHC Panel for patients diagnosed with colorectal cancer (CRC) to detect mismatch repair (MMR) proteins deficiency as an aid in the identification of probable Lynch syndrome and to detect BRAFV600E protein as an aid to differentiate between sporadic CRC and probable Lynch syndrome.

• #3 Lynch syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/lynch-syndrome/diagnosis-treatment/drc-20374719

  Diagnosing Lynch syndrome might start with a review of your family history of cancer. Your healthcare professional will want to know whether you or anyone in your family has had colon cancer, endometrial cancer and other cancers. This may lead to other tests and procedures to diagnose Lynch syndrome. […] Your healthcare professional may want you to consider genetic testing for Lynch syndrome if your family history has one or more of the following: […] If you or someone in your family has had cancer, a sample of the cancer cells might be tested. […] Positive IHC or MSI test results can show that the cancer cells have genetic changes that are connected to Lynch syndrome. But the results can’t say for certain whether you have Lynch syndrome. Some people have these genetic changes only in their cancer cells. This means the genetic changes weren’t inherited.

• #4 Lynch Syndrome – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1211/

  No consensus clinical diagnostic criteria for Lynch syndrome have been published. […] A diagnosis of Lynch syndrome should be suspected in a proband with: A diagnosis of a tumor of the Lynch syndrome spectrum (e.g., colorectal, endometrial, ovarian, stomach, small bowel, urinary tract [urothelial], biliary tract, prostate, brain [usually glioblastoma], skin [sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas], and pancreas) with one of the following on tumor tissue testing: Microsatellite instability (MSI) testing showing that tumor tissue is MSI high. […] The diagnosis of Lynch syndrome can be established in a proband by identification of a heterozygous germline pathogenic (or likely pathogenic) variant in one of the genes listed in Table 1 using molecular genetic testing.

• #5 Lynch Syndrome Testing

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/lynch-syndrome-testing/

  In their Genetic/Familial High-Risk Assessment: Colorectal, the NCCN lists the following criteria for the evaluation of Lynch Syndrome: Known LS pathogenic variant in the family. An individual with a LS-related cancer and any of the following: Diagnosed 50 y. A synchronous or metachronous LS-related cancer regardless of age. 1 first-degree or second-degree relative with LS-related cancer diagnosed 50 y. 2 first-degree or second-degree relatives with LS-related cancers regardless of age. Family history of any of the following: 1 first-degree relative with colorectal or endometrial cancer diagnosed 50 y. 1 first-degree relative with colorectal or endometrial cancer and a synchronous or metachronous LS-related cancer regardless of age. 2 first-degree or second-degree relatives with LS-related cancer including 1 diagnosed 50 y. 3 first-degree or second-degree relatives with LS-related cancers regardless of age. Increased model-predicted risk for LS. An individual with a 5% risk of having an MMR gene pathogenic variant based on predictive models (i.e., PREMM5, MMRpro, MMRpredict).

• #6 Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/188613-clinical

  Making the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome) is usually a three-stage process, including review of the family cancer history, tumor testing, and genetic testing. […] Significant suspicion for HNPCC should prompt further evaluation of the patient and his or her family. […] In 1990, following a conference in Amsterdam, the International Collaborative Group (ICG) first proposed clinical criteria to identify patients at risk of developing HNPCC. […] Amsterdam criteria I: Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first-degree relative (parent, child, sibling) of the other two. […] Amsterdam criteria II: Three or more family members with HNPCC-related cancers (colorectal, endometrial, small bowel, ureter, or renal pelvis), one of whom is a first-degree relative of the other two.

• #7 Hereditary Nonpolyposis Colorectal Cancer (Lynch Syndrome) Clinical Presentation: History, Physical Examination

  https://emedicine.medscape.com/article/188613-clinical

  Models have been developed for predicting the probability that a patient will have a pathogenic homozygous or heterozygous variant in a mismatch repair gene. […] The Bethesda guidelines, published in 1997 and revised in 2004, were designed to guide selection of colorectal tumors for microsatellite instability (MSI) testing. […] The Bethesda criteria may be more sensitive than either form of the Amsterdam criteria in identifying families with HNPCC.

• #8 Diagnosis Lynch Syndrome | Lynch Syndrome Center

  https://lynchsyndromecenter.ucsf.edu/diagnosis-lynch-syndrome

  Lynch syndrome dramatically increases the risk for cancer in a persons lifetime. […] It is important to diagnose and manage Lynch syndrome in order to prevent cancer or detect it early when it is most treatable. […] A diagnosis of Lynch syndrome can shine the light on potentially increased risk throughout a family. […] There is a process to diagnosing Lynch syndrome and it typically begins with a comprehensive review of the family medical history, which is sometimes followed by genetic testing. […] If the family history indicates the possibility of Lynch syndrome, the counselor might suggest further tests. […] There are two types of tests used for detecting Lynch syndrome: pathology tests and genetic blood tests. […] If Lynch syndrome is suspected, special pathology tests can be used to detect characteristics in tumors that may be caused by Lynch syndrome and can identify which gene may be responsible for Lynch syndrome in the family.

• #9 Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK431096/

  Personal or family history is critical in identifying patients at risk for Lynch syndrome. Persons who meet the criteria should undergo immunohistochemical and/or microsatellite analysis followed by germline DNA analysis for definitive diagnosis. […] Several tests may aid in diagnosing Lynch syndrome, including polymerase chain reaction (PCR) to assess for MSI, immunohistochemical staining (IHC) to assess for mismatch repair proteins, and germline sequencing. In addition, the common somatic mutation involving MLH1 promoter methylation is analyzed to help differentiate somatic vs germline etiology. […] Germline testing for Lynch syndrome is recommended in all tumors with abnormal MSI or IHS. IHC staining, utilizing antibodies against the 4 main repair proteins, can be used to predict the likelihood of MSI.

• #10 Lynch Syndrome Testing and Diagnosis – Digestive Cancers Europe

  https://digestivecancers.eu/rare-cancers/lynch-syndrome-testing-diagnosis/

  If you have been diagnosed with cancer, for example colorectal or endometrial cancer, a molecular screening test will probably be carried out on your tumour tissue to identify the likelihood of Lynch Syndrome. […] There are two types of molecular screening tests for Lynch Syndrome: Immunohistochemistry (IHC): A screening test for the proteins made by the MMR genes; if the genes are working properly, the proteins will be present. The absence of MMR proteins means an increased likelihood of Lynch Syndrome. […] Microsatellite Instability (MSI): A DNA analysis test checks if the MMR genes are working properly by looking at the stability of parts of the DNA, called microsatellites. A high MSI status means a high likelihood of Lynch Syndrome. […] After the molecular screening, you will have germline genetic testing to confirm the diagnosis. This involves a simple blood test, which will confirm if you have Lynch Syndrome or not. The result may take a few weeks.

• #11 Lynch Syndrome Detection | Lynch Syndrome Testing | MSI and Lynch Syndrome

  https://ch.promega.com/resources/technologies/microsatellite-instability-resource-center/lynch-syndrome-detection-testing/

  To determine if Lynch syndrome is likely, simple screening tests can be performed on tumor (cancer) tissue. The two most common tests are microsatellite instability testing (MSI) and immunohistochemistry testing (IHC) for major mismatch repair proteins (MMR). The results of these tests can indicate whether more specific genetic testing should be considered. […] High microsatellite instability (MSI-H) in tumor tissue is a hallmark of Lynch syndrome. MSI-H status indicates that certain sections of DNA called microsatellites have become unstable because the major mismatch repair proteins that correct errors during DNA replication are not functioning properly. A DNA analysis test is used to determine MSI status. The test is performed on both normal and tumor tissue. If the results for the tumor differ from the normal tissue results, the tumor is considered MSI-H.

• #12 Lynch Syndrome Testing

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/lynch-syndrome-testing/

  The following does not meet coverage criteria due to a lack of available published scientific literature confirming that the test(s) is/are required and beneficial for the diagnosis and treatment of an individuals illness. […] For all other purposes, including, but not limited to, testing of the general population, genetic testing for susceptibility to LS related cancer is NOT MEDICALLY NECESSARY. […] Currently, there exist two main approaches to diagnosing Lynch syndrome. One approach leverages molecular screening of colorectal and endometrial tumor specimens for evidence of defective MMR function (MMR-D) or high-level MSI (MSI-H) to identify patients with cancer who should undergo germline testing for pathogenic MMR gene variants. The other focuses on using direct germline testing performed on patients whose family histories of cancer are suspicious for Lynch syndrome. In recent years, molecular testing has gained traction for identification of individuals with Lynch syndrome due to its robust sensitivity and specificity, testing of which can be generalized into one of four categories: polymerase chain reaction (PCR)-based MSI testing, immunohistochemical staining (or immunohistochemistry [IHC]) for the MMR proteins, MLH1 promoter methylation analysis (or somatic BRAF V600E mutation analysis), and next-generation somatic (and/or germline) sequencing assays.

• #13 Lynch Syndrome Testing and Diagnosis – Digestive Cancers Europe

  https://digestivecancers.eu/rare-cancers/lynch-syndrome-testing-diagnosis/

  If you have been diagnosed with cancer, for example colorectal or endometrial cancer, a molecular screening test will probably be carried out on your tumour tissue to identify the likelihood of Lynch Syndrome. […] There are two types of molecular screening tests for Lynch Syndrome: Immunohistochemistry (IHC): A screening test for the proteins made by the MMR genes; if the genes are working properly, the proteins will be present. The absence of MMR proteins means an increased likelihood of Lynch Syndrome. […] Microsatellite Instability (MSI): A DNA analysis test checks if the MMR genes are working properly by looking at the stability of parts of the DNA, called microsatellites. A high MSI status means a high likelihood of Lynch Syndrome. […] After the molecular screening, you will have germline genetic testing to confirm the diagnosis. This involves a simple blood test, which will confirm if you have Lynch Syndrome or not. The result may take a few weeks.

• #14 Lynch Syndrome Detection | Lynch Syndrome Testing | MSI and Lynch Syndrome

  https://ch.promega.com/resources/technologies/microsatellite-instability-resource-center/lynch-syndrome-detection-testing/

  Immunohistochemistry is a screening test for Lynch syndrome tumors that looks for the proteins expressed by the major mismatch repair (MMR) genes. If the genes are functioning properly, the proteins will be present. Absence of a major mismatch repair protein increases the likelihood that Lynch syndrome is present.

• #15 LCD – Genetic Testing for Lynch Syndrome (L34912)

  https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=34912&ver=20

  This local coverage determination limits Lynch syndrome (LS) genetic testing to a stepped approach for Microsatellite Instability and Immunohistochemistry (MSI/IHC) screening, BRAF gene mutation, MLH1 gene promoter hypermethylation and targeted mismatch repair (MMR) germ-line gene testing to patients suspected of having LS. […] Patients with colorectal and/or endometrial cancer suspected of LS must undergo a comprehensive review of physical findings and a complete personal and family history. […] If a patient meets standards for LS testing in Step 1 (i.e., meets ACII or Revised Bethesda guidelines), the physician should proceed to Step 2 and 3. […] The use of IHC to detect loss of DNA mismatched repair (MMR) protein expression complements MSI to screen patients for defective MMR (DMMR), including both sporadic dMMR and LS dMMR.

• #16 Diagnosis and management of Lynch syndrome – American Gastroenterological AssociationAGA Logo_Horizontal

  https://gastro.org/clinical-guidance/diagnosis-and-management-of-lynch-syndrome/

  4. AGA suggests that in patients with colorectal cancer with IHC absent for MLH1, second-stage tumor testing for a BRAF mutation or for hypermethylation of the MLH1 promoter should be performed rather than proceeding directly to germline genetic testing. […] 5. AGA recommends surveillance colonoscopy (versus doing nothing) in persons with Lynch syndrome. […] 6. AGA suggests that surveillance colonoscopy should be performed every 1 to 2 years versus less frequent intervals. […] 7. AGA suggests that aspirin be offered for cancer prevention in patients with Lynch syndrome.

• #17 Lynch Syndrome Testing

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/lynch-syndrome-testing/

  The ASCP, CAP, AMP, and ASCO issued guidelines in 2017 stating BRAF p.V600 mutational analysis should be performed in deficient MMR tumors with loss of MLH1 to evaluate for Lynch Syndrome risk. Presence of a BRAF mutation strongly favors a sporadic pathogenesis. The absence of BRAF mutation does not exclude risk of Lynch syndrome. In addition, they have added the following recommendation for clinicians: clinicians should order mismatch repair status testing in patients with colorectal cancers for the identification of patients at high risk for Lynch syndrome and/or prognostic stratification. […] The American Society of Clinical Oncology (ASCO) recommends that genetic testing only be conducted in the setting of pre- and post-test counseling. In 2015, ASCO stated that identifying inherited mutations in genes such as BRCA1, BRCA2, and the genes associated with Lynch syndrome allows for interventions that can significantly reduce the development of cancer and improve survival.

• #18 Lynch Syndrome Testing

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/lynch-syndrome-testing/

  Likewise, the MMRpredict algorithm predicts the probability of a mutation carrier of an affected individual using criteria consisting of the age at time of diagnosis, gender, tumor location, synchronicity of tumor, and family history. A 2018 study shows that MMRpredict performs better than the PREMM5 model in identifying PMS2 mutation carriers, and the efficacy of the PREMM5 model is more dependent on the location of the tumor. Both algorithms were comparable in predicting MLH1 and MSH2 mutation carriers. These data apparently contradict earlier findings where a previous version of the PREMM model, PREMM1,2,6, performed better than MMRpredict in predicting carriers of MLH1, MSH2, or MSH6 gene mutations. For clinic- and population-based cohorts, O/E [observed-to-expected ratio] deviated from 1 for MMRPredict and MMRPro but were more satisfactory for PREMM1,2,6. MMRPro or PREMM1,2,6 predictions were clinically useful at thresholds of 5% or greater and in particular at greater than 15%.

• #19 Genetic Testing for Lynch Syndrome | Hereditary Colorectal (Colon) Cancer | CDC

  https://www.cdc.gov/colorectal-cancer-hereditary/testing/index.html

  Genetic testing looks for inherited genetic changes (mutations) that cause Lynch syndrome. […] Interpretation of genetic test results may vary depending on whether you have had colorectal cancer. […] If you had colorectal cancer or another cancer related to Lynch syndrome, here’s what the test results mean for you and your family: Positive test result: You have a genetic change that can cause Lynch syndrome. […] Negative test result: The test did not find a genetic change that increases your cancer risk. […] Negative genetic test result, but abnormal tumor screening: You could still have Lynch syndrome. […] Variant of uncertain significance (VUS): The test found a mutation in one of the genes associated with Lynch syndrome, but doctors don’t know if that mutation causes cancer. […] If you have a family history of colorectal cancer or other cancers related to Lynch syndrome but have not had cancer yourself, here’s what the test results mean for you and your family: Positive test result: You have a genetic change that can cause Lynch syndrome.

• #20 Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis – UpToDate

  https://www.uptodate.com/contents/lynch-syndrome-hereditary-nonpolyposis-colorectal-cancer-clinical-manifestations-and-diagnosis

  Lynch syndrome is the most common cause of inherited colorectal cancer (CRC). It is characterized by a significantly increased risk for CRC and endometrial cancer as well as a risk of several other malignancies. This topic will review the genetic basis, clinical manifestations, and diagnosis of Lynch syndrome. […] Lynch syndrome refers to patients and families with a germline mutation in one of the DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) or the EPCAM gene. […] Lynch syndrome is the most common inherited CRC susceptibility syndrome and accounts for approximately 3 percent of newly diagnosed cases of CRC and 2 to 3 percent of endometrial cancer. […] Lynch syndrome is an autosomal dominant disorder that is caused by a germline mutation in one of several DNA mismatch repair (MMR) genes or loss of expression of MSH2 due to deletion in the EPCAM gene.

• #21 Genetic Testing for Lynch Syndrome | Stanford Health Care

  https://stanfordhealthcare.org/medical-conditions/cancer/lynch-syndrome/hnpcc-diagnosis/genetic-testing.html

  HNPCC is also known as Lynch syndrome, or Cancer Family Syndrome. The majority of HNPCC is caused by mutations in one of several mismatch-repair genes: MSH2, MSH6, and PMS1 on chromosome 2, MLH1 on chromosome 3, MSH3 on chromosome 5, and PMS2 on chromosome 7. MSH2 and MLH1 account for the majority of mutations in HNPCC families. Mutations in any one of these genes confers an increased lifetime risk to develop colorectal cancer, as well as cancers of the endometrium, stomach, small intestine, liver and biliary tract, brain, ovary, ureters, and renal pelvis. Specifically, there is a 70-82% lifetime risk to develop colorectal cancer, a 12% chance to develop ovarian cancer, and up to a 60% chance to develop endometrial cancer. […] There are two approaches to performing genetic testing in families with suspected HNPCC. One approach is to proceed directly to mutation analysis of the MSH2, MLH1, and possibly MSH6 genes (testing a blood sample for germline mutations in these mismatch-repair genes). This approach is often taken when a family history clearly meets the criteria reviewed above. The second approach is to first test a tumor tissue sample for a characteristic called „microsatellite instability before considering mutation analysis”. Ninety percent of colorectal cancers from people with HNPCC exhibit MSI. If a tumor is found to exhibit MSI, then the patient/family may consider germline mutation testing of the mismatch-repair genes (MSH2, MLH1, and MSH6) for which commercial gene tests are available.

• #22 Genetic Testing for Lynch Syndrome | Stanford Health Care

  https://stanfordhealthcare.org/medical-conditions/cancer/lynch-syndrome/hnpcc-diagnosis/genetic-testing.html

  HNPCC is also known as Lynch syndrome, or Cancer Family Syndrome. The majority of HNPCC is caused by mutations in one of several mismatch-repair genes: MSH2, MSH6, and PMS1 on chromosome 2, MLH1 on chromosome 3, MSH3 on chromosome 5, and PMS2 on chromosome 7. MSH2 and MLH1 account for the majority of mutations in HNPCC families. Mutations in any one of these genes confers an increased lifetime risk to develop colorectal cancer, as well as cancers of the endometrium, stomach, small intestine, liver and biliary tract, brain, ovary, ureters, and renal pelvis. Specifically, there is a 70-82% lifetime risk to develop colorectal cancer, a 12% chance to develop ovarian cancer, and up to a 60% chance to develop endometrial cancer. […] There are two approaches to performing genetic testing in families with suspected HNPCC. One approach is to proceed directly to mutation analysis of the MSH2, MLH1, and possibly MSH6 genes (testing a blood sample for germline mutations in these mismatch-repair genes). This approach is often taken when a family history clearly meets the criteria reviewed above. The second approach is to first test a tumor tissue sample for a characteristic called „microsatellite instability before considering mutation analysis”. Ninety percent of colorectal cancers from people with HNPCC exhibit MSI. If a tumor is found to exhibit MSI, then the patient/family may consider germline mutation testing of the mismatch-repair genes (MSH2, MLH1, and MSH6) for which commercial gene tests are available.

• #23 Lynch Syndrome – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1211/

  Molecular genetic testing approaches can include a multigene panel or DNA methylation studies, and serial single-gene testing. Comprehensive genomic testing may also be considered. […] A multigene panel that includes MLH1, MSH2, MSH6, and PMS2 as well as EPCAM deletion analysis is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. […] The diagnosis of Lynch syndrome can be established in a proband by identification of a heterozygous germline pathogenic (or likely pathogenic) variant in one of the genes listed in Table 1 using molecular genetic testing.

• #24 Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK431096/

  Personal or family history is critical in identifying patients at risk for Lynch syndrome. Persons who meet the criteria should undergo immunohistochemical and/or microsatellite analysis followed by germline DNA analysis for definitive diagnosis. […] Several tests may aid in diagnosing Lynch syndrome, including polymerase chain reaction (PCR) to assess for MSI, immunohistochemical staining (IHC) to assess for mismatch repair proteins, and germline sequencing. In addition, the common somatic mutation involving MLH1 promoter methylation is analyzed to help differentiate somatic vs germline etiology. […] Germline testing for Lynch syndrome is recommended in all tumors with abnormal MSI or IHS. IHC staining, utilizing antibodies against the 4 main repair proteins, can be used to predict the likelihood of MSI.

• #25 Lynch Syndrome Factsheet – The Jackson Laboratory

  https://www.jax.org/education-and-learning/clinical-and-continuing-education/clinical-topics/cancer-resources/lynch-syndrome

  Germline molecular testing includes sequencing and deletion/duplication analysis of MLH1, MSH2, MSH6, PMS2, and EPCAM. Often these genes are analyzed as part of a larger multigene hereditary cancer panel. […] Meeting one or more of the criteria below warrants further risk assessment, genetic counseling and genetic testing as appropriate: Known LS mutation in family, Personal history of colorectal or endometrial cancer diagnosed before age 50, Personal history of a tumor with MMR deficiency at any age, An individual with a 2.5% risk of having a LS gene mutation using predictive models including those with a personal history of colorectal or endometrial cancer, 3 or more individuals with CRC or LS-associated cancers at any age, 2 individuals with CRC or LS-associated cancers, with at least one diagnosed before age 50 years.

• #26 Genetic Testing for Lynch Syndrome | Hereditary Colorectal (Colon) Cancer | CDC

  https://www.cdc.gov/colorectal-cancer-hereditary/testing/index.html

  Genetic testing looks for inherited genetic changes (mutations) that cause Lynch syndrome. […] Interpretation of genetic test results may vary depending on whether you have had colorectal cancer. […] If you had colorectal cancer or another cancer related to Lynch syndrome, here’s what the test results mean for you and your family: Positive test result: You have a genetic change that can cause Lynch syndrome. […] Negative test result: The test did not find a genetic change that increases your cancer risk. […] Negative genetic test result, but abnormal tumor screening: You could still have Lynch syndrome. […] Variant of uncertain significance (VUS): The test found a mutation in one of the genes associated with Lynch syndrome, but doctors don’t know if that mutation causes cancer. […] If you have a family history of colorectal cancer or other cancers related to Lynch syndrome but have not had cancer yourself, here’s what the test results mean for you and your family: Positive test result: You have a genetic change that can cause Lynch syndrome.

• #27 Lynch syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/lynch-syndrome/diagnosis-treatment/drc-20374719

  Genetic testing looks for changes in the genes that cause Lynch syndrome. You may give a sample of your blood for this test. […] A positive result means that a genetic change that causes Lynch syndrome was found in your cells. It doesn’t mean you’ll get cancer. But it does mean that your risk of certain cancers is higher than people who don’t have Lynch syndrome. […] A negative result means gene changes that cause Lynch syndrome weren’t found in your cells. It means you probably don’t have Lynch syndrome. But you could still have an increased risk of cancer. […] Genetic testing results don’t always give you a yes or no answer. Sometimes genetic testing finds a gene that healthcare professionals aren’t sure about. A genetics professional can tell you what this means for your health. […] If your healthcare professional thinks you could have Lynch syndrome, they may suggest that you meet with a genetics professional, such as a genetic counselor. […] A genetics professional can help you decide whether genetic testing would be useful for you. If you choose to have the test, they can help you understand your results.

• #28 Lynch Syndrome | Personalized Care | Columbia Surgery

  https://columbiasurgery.org/conditions-and-treatments/lynch-syndrome

  If a patient has a family history of colon cancer, endometrial cancer, or a related cancer, and/or meets one or more of the criteria listed in the Bethesda guidelines above, doctors may recommend further tests to diagnose Lynch syndrome. […] If cancer is already present in the patient or a family member, a small sample of the tumor (a biopsy) can be removed and tested to determine if it was caused by gene mutations related to Lynch syndrome. […] While both of these tests can show an increased likelihood for Lynch syndrome, neither can definitively diagnose it. Instead, patients will need to undergo more specific genetic testing. […] Genetic testing looks for DNA mutations using either a small sample of blood or a swab from the inside of the mouth. Testing will show one of three possibilities: Positive Result: This indicates a gene mutation associated with Lynch syndrome has been discovered. However, it does not mean a patient has or will have cancer. Negative Result: This indicates a gene mutation associated with Lynch syndrome has not been discovered. However, a patient may still have an increased likelihood of having cancer, especially if they have a family history of cancer. Undetermined Result: This result can occur if a variation is detected that is not associated with Lynch syndrome. In this case, a genetic counselor can help explain the significance of the result.

• #29 Genetic Testing for Lynch Syndrome | Hereditary Colorectal (Colon) Cancer | CDC

  https://www.cdc.gov/colorectal-cancer-hereditary/testing/index.html

  Negative test result: The test did not find a genetic change that increases your cancer risk. […] Negative test result for the genetic change that runs in your family: You do not have the genetic change that runs in your family. […] Variant of uncertain significance (VUS): The test found a mutation in one of the genes associated with Lynch syndrome, but doctors don’t know if that mutation causes cancer. […] Having a family history of colorectal, uterine, and other cancers does not mean you have Lynch syndrome.

• #30 Lynch syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/lynch-syndrome/diagnosis-treatment/drc-20374719

  Genetic testing looks for changes in the genes that cause Lynch syndrome. You may give a sample of your blood for this test. […] A positive result means that a genetic change that causes Lynch syndrome was found in your cells. It doesn’t mean you’ll get cancer. But it does mean that your risk of certain cancers is higher than people who don’t have Lynch syndrome. […] A negative result means gene changes that cause Lynch syndrome weren’t found in your cells. It means you probably don’t have Lynch syndrome. But you could still have an increased risk of cancer. […] Genetic testing results don’t always give you a yes or no answer. Sometimes genetic testing finds a gene that healthcare professionals aren’t sure about. A genetics professional can tell you what this means for your health. […] If your healthcare professional thinks you could have Lynch syndrome, they may suggest that you meet with a genetics professional, such as a genetic counselor. […] A genetics professional can help you decide whether genetic testing would be useful for you. If you choose to have the test, they can help you understand your results.

• #31 Genetic Testing for Lynch Syndrome | Hereditary Colorectal (Colon) Cancer | CDC

  https://www.cdc.gov/colorectal-cancer-hereditary/testing/index.html

  Genetic testing is recommended if you have had colorectal (colon) or uterine (endometrial) cancer and have abnormal tumor screening results. […] Your genetic counselor or other health care provider may recommend genetic testing based on your personal and family history of cancer and whether you have a family member with Lynch syndrome. […] Genetic testing for Lynch syndrome can confirm your diagnosis if your tumor screening results are abnormal. […] Knowing if you have Lynch syndrome can help you and your family members understand and manage your risk for cancers related to Lynch syndrome. […] Genetic counseling before genetic testing is important to find out if you and your family are likely to benefit from genetic testing for Lynch syndrome. […] Usually, genetic testing will be recommended if your tumor screening results are abnormal.

• #32 Lynch syndrome – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/lynch-syndrome/diagnosis-treatment/drc-20374719

  Genetic testing looks for changes in the genes that cause Lynch syndrome. You may give a sample of your blood for this test. […] A positive result means that a genetic change that causes Lynch syndrome was found in your cells. It doesn’t mean you’ll get cancer. But it does mean that your risk of certain cancers is higher than people who don’t have Lynch syndrome. […] A negative result means gene changes that cause Lynch syndrome weren’t found in your cells. It means you probably don’t have Lynch syndrome. But you could still have an increased risk of cancer. […] Genetic testing results don’t always give you a yes or no answer. Sometimes genetic testing finds a gene that healthcare professionals aren’t sure about. A genetics professional can tell you what this means for your health. […] If your healthcare professional thinks you could have Lynch syndrome, they may suggest that you meet with a genetics professional, such as a genetic counselor. […] A genetics professional can help you decide whether genetic testing would be useful for you. If you choose to have the test, they can help you understand your results.

• #33 Lynch syndrome – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/lynch-syndrome/symptoms-causes/syc-20374714

  People with Lynch syndrome may need careful testing to look for cancer when it’s small. […] Ask your healthcare professional to help set up an appointment with a professional trained in genetics, such as a genetic counselor. This person can help you understand Lynch syndrome, what causes it and whether genetic testing is right for you. […] Lynch syndrome is caused by genes that are passed from parents to children. […] People with Lynch syndrome have mismatch repair genes that don’t work as expected. If an error happens in the DNA, it might not get fixed. This could cause cells that grow out of control and become cancer cells. […] A genetics professional can help you come up with a plan for talking about this with your children. The plan might include how and when to tell them and when they should consider testing.

• #34 Genetic Testing for Lynch Syndrome | Hereditary Colorectal (Colon) Cancer | CDC

  https://www.cdc.gov/colorectal-cancer-hereditary/testing/index.html

  Genetic testing is recommended if you have had colorectal (colon) or uterine (endometrial) cancer and have abnormal tumor screening results. […] Your genetic counselor or other health care provider may recommend genetic testing based on your personal and family history of cancer and whether you have a family member with Lynch syndrome. […] Genetic testing for Lynch syndrome can confirm your diagnosis if your tumor screening results are abnormal. […] Knowing if you have Lynch syndrome can help you and your family members understand and manage your risk for cancers related to Lynch syndrome. […] Genetic counseling before genetic testing is important to find out if you and your family are likely to benefit from genetic testing for Lynch syndrome. […] Usually, genetic testing will be recommended if your tumor screening results are abnormal.

• #35 Lynch Syndrome: Signs/Symptoms, Causes, Outlook

  https://my.clevelandclinic.org/health/diseases/17195-lynch-syndrome-and-hnpcc

  Lynch syndrome is a genetic condition that can lead to cancer. People with Lynch syndrome often get cancer before age 50 and should undergo lifelong cancer screenings to detect and treat cancer early. […] Individuals diagnosed with Lynch syndrome should tell their family members and encourage them to seek genetic counseling. Genetic counseling helps you and your family understand the risks of having a child with a genetic condition. Counseling includes an evaluation of their personal and family history as well as and genetic testing for the Lynch syndrome gene mutation. […] Your healthcare provider will offer prenatal screening tests and genetic testing to diagnose Lynch syndrome before your baby is born. Genetic tests can help diagnose your child after they are born as well. […] If you have a Lynch syndrome diagnosis, your healthcare provider will offer regular tests to check for cancer. Tests to detect common cancers associated with Lynch syndrome include: Colonoscopy: A colonoscopy examines the inside of your large intestine, colon and rectum with a camera attached to a scope. Your healthcare provider will recommend scheduling a colonoscopy every one to two years.

• #36

  https://www.cancervic.org.au/cancer-information/genetics-and-risk/lynch-syndrome

  The second step in getting tested for Lynch syndrome is to speak to your doctor or surgeon. They will be able to advise you on the need for genetic testing for yourself or within your family. […] If it is decided that genetic testing is appropriate, you will be referred to the familial cancer service (which may be public or private) in your state. […] If you decide to go ahead with genetic testing, a DNA sample (blood or otherwise) will be collected and analysed in a laboratory. […] If you receive a diagnosis of Lynch syndrome, you will be told which of the genes is mutated in your family. It’s important to know this because your gene variant can affect your chance of developing cancer and therefore the surveillance management you will need to undertake. […] If a family member has been confirmed to have Lynch syndrome, predictive testing can be offered to other relatives on the affected side of the family.

• #37 You’ve Been Diagnosed With Lynch Syndrome. Now What? | ACOG

  https://www.acog.org/womens-health/experts-and-stories/the-latest/youve-been-diagnosed-with-lynch-syndrome-now-what

  If you are faced with these decisions, ask your ob-gyn for a referral to a fertility specialist who can help you explore your options. […] A hereditary cancer syndrome diagnosis can prompt other blood relatives to get genetic testing. We call this cascade testing. […] There is no medical reason to test them before they turn 18. After this age, they can decide for themselves whether to get tested. […] Lynch syndrome is something that happens to you, even if that thing isn’t cancer. You have a lifetime to live with it, and that’s part of what makes previvorship so hard, physically and emotionally.

• #38 You’ve Been Diagnosed With Lynch Syndrome. Now What? | ACOG

  https://www.acog.org/womens-health/experts-and-stories/the-latest/youve-been-diagnosed-with-lynch-syndrome-now-what

  If you are faced with these decisions, ask your ob-gyn for a referral to a fertility specialist who can help you explore your options. […] A hereditary cancer syndrome diagnosis can prompt other blood relatives to get genetic testing. We call this cascade testing. […] There is no medical reason to test them before they turn 18. After this age, they can decide for themselves whether to get tested. […] Lynch syndrome is something that happens to you, even if that thing isn’t cancer. You have a lifetime to live with it, and that’s part of what makes previvorship so hard, physically and emotionally.

• #39 Lynch Syndrome Testing

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/lynch-syndrome-testing/

  The ASCP, CAP, AMP, and ASCO issued guidelines in 2017 stating BRAF p.V600 mutational analysis should be performed in deficient MMR tumors with loss of MLH1 to evaluate for Lynch Syndrome risk. Presence of a BRAF mutation strongly favors a sporadic pathogenesis. The absence of BRAF mutation does not exclude risk of Lynch syndrome. In addition, they have added the following recommendation for clinicians: clinicians should order mismatch repair status testing in patients with colorectal cancers for the identification of patients at high risk for Lynch syndrome and/or prognostic stratification. […] The American Society of Clinical Oncology (ASCO) recommends that genetic testing only be conducted in the setting of pre- and post-test counseling. In 2015, ASCO stated that identifying inherited mutations in genes such as BRCA1, BRCA2, and the genes associated with Lynch syndrome allows for interventions that can significantly reduce the development of cancer and improve survival.

• #40 Lynch Syndrome Testing

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/lynch-syndrome-testing/

  In 2023, ASCO endorsed the College of American Pathologists (CAP) Guidelines on testing for mismatch repair (MMR) and microsatellite instability (MSI) for patients considered for immune checkpoint inhibitor therapy: For cancer patients being considered for immune checkpoint inhibitor therapy, if a MMR deficiency consistent with Lynch syndrome is identified in the tumor, pathologists should communicate this finding to the treating physician. […] The 2014 U.S. Multi-Society Task Force guidelines on colorectal cancer are captured below. Testing for MMR deficiency of newly diagnosed CRC should be performed. This can be done for all CRCs, or CRC diagnosed at age 70 years or younger, and in individuals older than 70 years who have a family history concerning for LS. […] Updated 2017 guidelines from the U.S. Multi-Society Task Force give the following guideline for colorectal cancer screening and LS: colonoscopy is recommended at 10-year intervals in average-risk persons and at 1- to 2-year intervals in those with Lynch syndrome.

• #41 Diagnosis and management of Lynch syndrome – American Gastroenterological AssociationAGA Logo_Horizontal

  https://gastro.org/clinical-guidance/diagnosis-and-management-of-lynch-syndrome/

  Advice for diagnosing and managing Lynch syndrome, the most common heritable colorectal cancer (CRC) syndrome. […] 1. In patients without a personal history of colorectal or another cancer but with a family history suggestive of Lynch syndrome, AGA suggests that risk prediction models be offered rather than doing nothing. […] 2. In patients without a personal history of colorectal or another cancer but with a family history suggestive of Lynch syndrome, AGA suggests that risk prediction models be offered rather than proceeding directly with germline genetic testing. […] 3. AGA recommends testing the tumors of all patients with colorectal cancer with either immunohistochemistry (IHC) or for microsatellite instability (MSI) to identify potential cases of Lynch syndrome versus doing no testing for Lynch syndrome.

• #42 Diagnosis and management of Lynch syndrome | Frontline Gastroenterology

  https://fg.bmj.com/content/13/e1/e80

  Lynch syndrome (LS) is a dominantly inherited cancer susceptibility syndrome defined by presence of pathogenic variants in DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2, or in deletions of the EPCAM gene. […] Therefore, testing for LS in all new diagnoses of colorectal or endometrial cancers is now recommended in the UK, and gastroenterologists can offer mainstreamed genetic testing for LS to patients with cancer. […] All new diagnoses of colorectal or endometrial cancer should be assessed for potential LS with mismatch repair (MMR) testing, and where defective, should trigger referral for constitutional MMR gene testing. […] Gastroenterologists and other non-genetics service clinicians may now offer mainstreamed genetic testing for LS to patients with cancer. […] The optimal pathway is that genomic testing be offered locally by the gastroenterologist, or other CRC multidisciplinary team (MDT) member, a process called mainstreaming, but patients may alternatively be referred to a clinical genetics team.

• #43 Lynch Syndrome Testing

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/lynch-syndrome-testing/

  The NCCN considers LS-related cancers to include colorectal, endometrial, gastric, ovarian, pancreas, urothelial, brain (usually glioblastoma), biliary tract, and small intestinal cancers, as well as sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas as seen in Muir-Torre syndrome. When there is no known familial mutation, the NCCN recommends germline multigene panel test (MGPT) evaluation for LS and other hereditary cancer syndromes. The NCCN also recommends tumor screening for MMR deficiency for all CRC and endometrial cancers regardless of age at diagnosis. […] NICE, in 2017, released their guidelines concerning molecular testing for LS in people with CRC. The recommend the following: Offer testing to all people with colorectal cancer, when first diagnosed, using immunohistochemistry for mismatch repair proteins or microsatellite instability testing to identify tumors with deficient DNA mismatch repair, and to guide further sequential testing for Lynch syndrome.

• #44 Lynch syndrome — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/lynch-syndrome/

  Lynch syndrome may be suspected from a family history of bowel cancer and other Lynch syndrome-related cancers, triggering genomic testing in the family. […] NICE guidelines recommend screening all colorectal cancers and all endometrial cancers for Lynch syndrome at first diagnosis. […] Colorectal cancers may be screened for Lynch syndrome using either: immunohistochemistry (IHC) to identify loss of expression of MMR proteins; or MSI testing. […] Depending on the assay used, MSI testing is less sensitive in endometrial cancer, so these tumours should be screened for Lynch syndrome using IHC testing to check for MMR deficiency. […] Genomic testing for underlying constitutional (germline) MMR gene variants is guided by the results of MSI and/or IHC testing. […] Gene panel tests are available for the MMR genes and/or other colorectal cancer predisposition genes.

• #45 Lynch Syndrome Testing

  https://www.southcarolinablues.com/web/public/brands/medicalpolicy/external-policies/lynch-syndrome-testing/

  The following does not meet coverage criteria due to a lack of available published scientific literature confirming that the test(s) is/are required and beneficial for the diagnosis and treatment of an individuals illness. […] For all other purposes, including, but not limited to, testing of the general population, genetic testing for susceptibility to LS related cancer is NOT MEDICALLY NECESSARY. […] Currently, there exist two main approaches to diagnosing Lynch syndrome. One approach leverages molecular screening of colorectal and endometrial tumor specimens for evidence of defective MMR function (MMR-D) or high-level MSI (MSI-H) to identify patients with cancer who should undergo germline testing for pathogenic MMR gene variants. The other focuses on using direct germline testing performed on patients whose family histories of cancer are suspicious for Lynch syndrome. In recent years, molecular testing has gained traction for identification of individuals with Lynch syndrome due to its robust sensitivity and specificity, testing of which can be generalized into one of four categories: polymerase chain reaction (PCR)-based MSI testing, immunohistochemical staining (or immunohistochemistry [IHC]) for the MMR proteins, MLH1 promoter methylation analysis (or somatic BRAF V600E mutation analysis), and next-generation somatic (and/or germline) sequencing assays.

• #46 Diagnosis and management of Lynch syndrome | Frontline Gastroenterology

  https://fg.bmj.com/content/13/e1/e80

  Since 2017, universal testing of all new CRC diagnoses is recommended by the National Institute of Health and Care Excellence (NICE). […] All CRCs should undergo testing for mismatch repair deficiency (dMMR) testing on their tumour specimen, preferably on colonoscopic biopsies where possible. […] The presence of dMMR indicates faulty DNA replication base pair mismatches, which have not been repaired. […] Loss of protein expression of MMR proteins on immunohistochemistry (IHC) testing of cancers may indicate that the underlying gene requires testing. […] If a tumour is dMMR with either abnormal IHC, or MSI, and no evidence of MLH1 promotor methylation, the patient is eligible for genetic testing for LS. […] The cumulative lifetime incidence of CRC in people with LS (MLH1 45%, MSH2 35%, MSH6 20% PMS2 14%) is considerably higher than in the general population.

• #47 LCD – Genetic Testing for Lynch Syndrome (L34912)

  https://www.cms.gov/medicare-coverage-database/view/lcd.aspx?lcdId=34912&ver=20

  This local coverage determination limits Lynch syndrome (LS) genetic testing to a stepped approach for Microsatellite Instability and Immunohistochemistry (MSI/IHC) screening, BRAF gene mutation, MLH1 gene promoter hypermethylation and targeted mismatch repair (MMR) germ-line gene testing to patients suspected of having LS. […] Patients with colorectal and/or endometrial cancer suspected of LS must undergo a comprehensive review of physical findings and a complete personal and family history. […] If a patient meets standards for LS testing in Step 1 (i.e., meets ACII or Revised Bethesda guidelines), the physician should proceed to Step 2 and 3. […] The use of IHC to detect loss of DNA mismatched repair (MMR) protein expression complements MSI to screen patients for defective MMR (DMMR), including both sporadic dMMR and LS dMMR.

• #48 Diagnosis and management of Lynch syndrome – American Gastroenterological AssociationAGA Logo_Horizontal

  https://gastro.org/clinical-guidance/diagnosis-and-management-of-lynch-syndrome/

  Advice for diagnosing and managing Lynch syndrome, the most common heritable colorectal cancer (CRC) syndrome. […] 1. In patients without a personal history of colorectal or another cancer but with a family history suggestive of Lynch syndrome, AGA suggests that risk prediction models be offered rather than doing nothing. […] 2. In patients without a personal history of colorectal or another cancer but with a family history suggestive of Lynch syndrome, AGA suggests that risk prediction models be offered rather than proceeding directly with germline genetic testing. […] 3. AGA recommends testing the tumors of all patients with colorectal cancer with either immunohistochemistry (IHC) or for microsatellite instability (MSI) to identify potential cases of Lynch syndrome versus doing no testing for Lynch syndrome.

• #49 Lynch Syndrome: Signs/Symptoms, Causes, Outlook

  https://my.clevelandclinic.org/health/diseases/17195-lynch-syndrome-and-hnpcc

  Treatment for Lynch syndrome focuses on detecting cancer and surgically removing it from your body. […] Currently, there is no cure for Lynch syndrome. The best prognosis occurs if your healthcare provider finds and removes cancer early before it has time to spread to other parts of your body. Annual screenings, like a colonoscopy, are highly recommended for people diagnosed with Lynch syndrome. […] If you have Lynch syndrome, its important that you visit your healthcare provider for annual checkups and work with your provider to schedule regular screening tests to detect cancer early.

• #50 Diagnosis and management of Lynch syndrome – American Gastroenterological AssociationAGA Logo_Horizontal

  https://gastro.org/clinical-guidance/diagnosis-and-management-of-lynch-syndrome/

  4. AGA suggests that in patients with colorectal cancer with IHC absent for MLH1, second-stage tumor testing for a BRAF mutation or for hypermethylation of the MLH1 promoter should be performed rather than proceeding directly to germline genetic testing. […] 5. AGA recommends surveillance colonoscopy (versus doing nothing) in persons with Lynch syndrome. […] 6. AGA suggests that surveillance colonoscopy should be performed every 1 to 2 years versus less frequent intervals. […] 7. AGA suggests that aspirin be offered for cancer prevention in patients with Lynch syndrome.

• #51 Diagnosis and management of Lynch syndrome | Frontline Gastroenterology

  https://fg.bmj.com/content/13/e1/e80

  Patients with LS have an accelerated pathway to carcinogenesis compared with the general population. […] As such, colorectal surveillance with routine colonoscopy every 2 years should start at 25 years for MLH1 and MSH2 carriers or at 35 years for MSH6 and PMS2 gene carriers. […] The typical age of onset of gynaecological cancer in LS is after age 40 years (with 5% patients younger than 40 years); therefore, women should be counselled on consideration of risk-reducing hysterectomy and removal of ovaries at age 40 years (for MLH1, MSH2 and MSH6 variant carriers).

• #52 Colorectal Cancer Genetic Testing | Lynch Syndrome Testing | American Cancer Society

  https://www.cancer.org/cancer/types/colon-rectal-cancer/causes-risks-prevention/genetic-tests-screening-prevention.html

  In families known to carry a Lynch syndrome gene mutation, doctors recommend that family members who have tested positive for the mutation and those who have not been tested should start colonoscopy screening during their early 20s, or 2 to 5 years younger than the youngest person in the family with a diagnosis (whichever is earlier). Testing should be done every 1 or 2 years. This way polyps can be found and removed, and any cancers can be found at the earliest possible stage.

• #53 Lynch Syndrome Facts –

  https://www.lynchscreening.net/implementation/follow-up-germline-testing/lynch-fact-sheets/

  Lynch Syndrome is caused by autosomal dominantly inherited mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. […] Recommended screening colonoscopy every 1-2 years beginning at age 25 has been demonstrated to substantially reduce (50%) CRC incidence and mortality. […] Previous studies have demonstrated the clinical utility and cost effectiveness of screening for Lynch Syndrome all newly diagnosed CRCs. […] Screening performed on pathology specimens utilizing immunohistochemistry (IHC) for the 4 MMR proteins, and/or molecular microsatellite instability (MSI) testing can identify 95% of Lynch Syndrome-associated CRCs. […] Referral of patients with abnormal screen results for genetic counseling and molecular testing for germline MMR mutations allows for diagnostic confirmation for the patient, and accurate testing for family members. […] Screening for Lynch Syndrome on all newly diagnosed colorectal cancers has been recommended by the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group, is a Healthy People 2020 Objective, and is currently being performed in 100s of facilities nationwide.

• #54 Managing Lynch Syndrome | Lynch Syndrome Center

  https://lynchsyndromecenter.ucsf.edu/managing-lynch-syndrome

  Individuals with Lynch syndrome are advised to undergo colonoscopy screening every 1-2 years. […] More frequent surveillance may be recommended based on any high-risk endoscopic findings. […] According to the NCCN guidelines, upper endoscopy GI surveillance with EGD starting at age 30-40 years and repeated every 2-4 years is recommended. […] The NCCN has determined that screening may be considered at the clinicians discretion. […] Some physicians choose to use both transvaginal ultrasound and the serum CA-125 test together in order to screen for ovarian cancer in women with Lynch syndrome. […] Women with Lynch syndrome are at an increased risk of developing uterine cancer, the NCCN guidelines state that because there is no clear evidence to support screening for uterine cancer in this population.

• #55 Managing Lynch Syndrome | Lynch Syndrome Center

  https://lynchsyndromecenter.ucsf.edu/managing-lynch-syndrome

  However, endometrial biopsy is both highly sensitive and highly specific as a diagnostic procedure and endometrial biopsy every 1-2 years starting at age 30-35 can be considered. […] Some surgical options for preventing cancer include: […] A hysterectomy refers to surgical removal of the uterus. […] An oophorectomy is a surgical procedure to remove the ovaries, which reduces the risk of ovarian cancer. […] The best way to treat cancer is to prevent it from occurring in the first place. […] Because Lynch syndrome increases the risk of certain types of cancer, preventive strategies are of the utmost importance.

• #56 Lynch Syndrome | Colorectal Cancer Alliance

  https://colorectalcancer.org/screening-prevention/prevention/genetic-and-inherited-conditions/lynch-syndrome

  It is important that you tell your family members about your diagnosis so they can talk to their doctors. […] Your family members can be tested for Lynch syndrome even if they do not have cancer. […] People with Lynch syndrome should get screened early and often. Talk with your doctor about a screening plan to reduce your risk of developing colorectal or other cancers. […] Women with Lynch syndrome should have a screening plan for endometrial cancer and ovarian cancer that includes an annual: Transvaginal ultrasound, Blood test for the CA125 biomarker.

• #57 You’ve Been Diagnosed With Lynch Syndrome. Now What? | ACOG

  https://www.acog.org/womens-health/experts-and-stories/the-latest/youve-been-diagnosed-with-lynch-syndrome-now-what

  Depending on which Lynch mutation you have, doctors may recommend colonoscopies every 1 to 2 years. Endometrial biopsies may be recommended every 1 to 2 years, starting between age 30 and 35. Other screenings may also be recommended based on your genetics and family history. […] Screening guidelines for Lynch syndrome are continually changing, so it’s helpful to have yearly appointments with a doctor that you trust to navigate the changes. […] We recommend all these screenings because, if you do develop cancer, finding it early can make it easier to treat. […] With Lynch syndrome, you’ll have to make many decisions about your health and your future. […] Ideally, you and your doctor should discuss removal of your ovaries and uterus by your mid-40s. Until then, we can reduce your risk for these cancers through lifestyle changes, hormonal medications, and other measures.

• #58 My Lynch Syndrome Diagnosis: A Diagnosis Diaries Story

  https://www.healthline.com/health/my-lynch-syndrome-diagnosis

  In addition to colorectal cancer and endometrial cancer (at least Id already survived that one), people with Lynch syndrome are also more likely to get stomach, bladder, ovarian (another one out of the way!), pancreatic, and prostate cancers, among others. […] The five gene mutations that are part of Lynch each have their own set of statistics about how likely a patient is to be diagnosed with various cancers. […] Four of the five genes associated with Lynch are known as mismatch repair genes. […] Lynch is one of the most common genetic mutations. About 1 in every 300 people have Lynch. […] If you know you have Lynch, vigilance and lots of screening are key to catching cancers at an early stage or even eliminating them before they start. […] Women with Lynch who are done with childbearing are encouraged to have hysterectomies and their ovaries removed to ensure they dont have to go through what I did with ovarian and endometrial cancers. […] Only about 50% of people diagnosed with ovarian cancer live for 5 years or longer after their diagnosis.

• #59 Lynch Syndrome: Signs/Symptoms, Causes, Outlook

  https://my.clevelandclinic.org/health/diseases/17195-lynch-syndrome-and-hnpcc

  Treatment for Lynch syndrome focuses on detecting cancer and surgically removing it from your body. […] Currently, there is no cure for Lynch syndrome. The best prognosis occurs if your healthcare provider finds and removes cancer early before it has time to spread to other parts of your body. Annual screenings, like a colonoscopy, are highly recommended for people diagnosed with Lynch syndrome. […] If you have Lynch syndrome, its important that you visit your healthcare provider for annual checkups and work with your provider to schedule regular screening tests to detect cancer early.

• #60 Diagnosis and management of Lynch syndrome – American Gastroenterological AssociationAGA Logo_Horizontal

  https://gastro.org/clinical-guidance/diagnosis-and-management-of-lynch-syndrome/

  4. AGA suggests that in patients with colorectal cancer with IHC absent for MLH1, second-stage tumor testing for a BRAF mutation or for hypermethylation of the MLH1 promoter should be performed rather than proceeding directly to germline genetic testing. […] 5. AGA recommends surveillance colonoscopy (versus doing nothing) in persons with Lynch syndrome. […] 6. AGA suggests that surveillance colonoscopy should be performed every 1 to 2 years versus less frequent intervals. […] 7. AGA suggests that aspirin be offered for cancer prevention in patients with Lynch syndrome.

• #61 NHS England » Life-saving NHS test helping to diagnose thousands with cancer-causing syndrome

  https://www.england.nhs.uk/2023/04/life-saving-nhs-test-helping-to-diagnose-thousands-with-cancer-causing-syndrome/

  NHS England, through the NHS Genomic Medicine Service, has launched a national transformation project to ensure more patients with Lynch syndrome are identified and benefit from regular check-ups, earlier interventions and more targeted treatment, such as combinations of immunotherapy, chemotherapy and surgeries. […] The NHS is now able to identify the condition through a simple blood test, which then goes through a regional genomic laboratory hub, is sequenced, and then sent back to the referring clinician. […] A positive diagnosis also means doctors can improve the chances of staying cancer free with interventions like aspirin, which can reduce the risk of bowel cancer developing by up to 50 per cent, regular colonoscopies to check for changes to healthy cells and offering women preventative gynaecological surgery.

• #62 NHS England » Life-saving NHS test helping to diagnose thousands with cancer-causing syndrome

  https://www.england.nhs.uk/2023/04/life-saving-nhs-test-helping-to-diagnose-thousands-with-cancer-causing-syndrome/

  A life-saving NHS testing programme is helping to diagnose thousands of people with a genetic condition that increases the chance of developing cancer. […] The health service has begun rolling out a genetic test for Lynch syndrome, an inherited condition that increases the risk of certain cancers, including bowel, ovarian and pancreatic. […] The national programme ensures all people diagnosed with bowel and endometrial are offered genomic testing, with a diagnosis for Lynch syndrome not only helping to guide more personalised cancer treatment but enabling their families and relatives to be offered testing too. […] Those with Lynch syndrome who are diagnosed with bowel cancer tend to have tumours that are more responsive to immunotherapies such as pembrolizumab, with the genetic testing enabling them to receive the best treatment for their cancer and giving them the best chance of survival.

• #63 Lynch Syndrome Testing and Diagnosis – Digestive Cancers Europe

  https://digestivecancers.eu/rare-cancers/lynch-syndrome-testing-diagnosis/

  Because Lynch Syndrome is silent and without symptoms, until it causes cancer, most people who have it are unaware. Indeed, it is estimated that 95% of people with Lynch Syndrome are not aware they have it. […] The biggest sign that you could have Lynch Syndrome is your familys medical history. If for example, several members of your family have been diagnosed with colorectal or endometrial cancer, particularly before the age of 50, then your doctor may advise testing for Lynch Syndrome. […] If you have been diagnosed with colorectal or endometrial cancer yourself especially below the age of 50 then your doctor may also advise testing for Lynch Syndrome. European guidelines recommend that all patients with colorectal cancer are tested for Lynch Syndrome. […] The type of tests you will undergo for Lynch Syndrome will depend on whether you have already been diagnosed with cancer.

• #64 Lynch Syndrome and the Challenge of Getting a Diagnosis – Digestive Cancers Europe

  https://digestivecancers.eu/lynch-syndrome-and-the-challenge-of-getting-a-diagnosis/

  Lynch Syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary condition characterised by a high risk of various cancers. […] Its estimated that 95% of people with Lynch Syndrome are unaware that they have it. […] Diagnosing Lynch Syndrome typically involves genetic testing to detect mutations in specific genes. […] Moreover, access to genetic testing for Lynch Syndrome may not be easy or affordable for everyone. […] To overcome these difficulties, we need doctors and healthcare teams to know more about Lynch Syndrome, provide more accessible ways for people to get genetic testing, and offer simpler ways to find out if someone might have Lynch Syndrome and if theyre at risk.

• #65

  https://www.cancervic.org.au/cancer-information/genetics-and-risk/lynch-syndrome

  This is important as it gives family members the opportunity to learn whether they too have a greater chance of developing cancer in their lifetime. […] Lynch syndrome is extremely underdiagnosed. Although Lynch syndrome is identified in approximately 3% of all colorectal cancers (CRCs), it is estimated that roughly 90% of Lynch syndrome carriers are unaware of their Lynch syndrome status. […] Today, however, all cancers of the bowel and endometrium should be tested for the signature of Lynch syndrome as there may not be a family history nor early aged onset of the cancer. […] A cancer family history is an important diagnostic tool, however using these criteria may fail to identify some families with Lynch syndrome; particularly where family size is small or where knowledge of family cancer history is incomplete. […] If a patient meets the above listed criteria, or has the Lynch syndrome signature of mismatch repair deficiency in their colorectal or endometrial cancer at any age, they should be referred immediately to a Family Cancer Clinic.

• #66 Lynch Syndrome and the Challenge of Getting a Diagnosis – Digestive Cancers Europe

  https://digestivecancers.eu/lynch-syndrome-and-the-challenge-of-getting-a-diagnosis/

  Lynch Syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a hereditary condition characterised by a high risk of various cancers. […] Its estimated that 95% of people with Lynch Syndrome are unaware that they have it. […] Diagnosing Lynch Syndrome typically involves genetic testing to detect mutations in specific genes. […] Moreover, access to genetic testing for Lynch Syndrome may not be easy or affordable for everyone. […] To overcome these difficulties, we need doctors and healthcare teams to know more about Lynch Syndrome, provide more accessible ways for people to get genetic testing, and offer simpler ways to find out if someone might have Lynch Syndrome and if theyre at risk.

• #67 Lynch Syndrome Testing and Diagnosis – Digestive Cancers Europe

  https://digestivecancers.eu/rare-cancers/lynch-syndrome-testing-diagnosis/

  Because Lynch Syndrome is silent and without symptoms, until it causes cancer, most people who have it are unaware. Indeed, it is estimated that 95% of people with Lynch Syndrome are not aware they have it. […] The biggest sign that you could have Lynch Syndrome is your familys medical history. If for example, several members of your family have been diagnosed with colorectal or endometrial cancer, particularly before the age of 50, then your doctor may advise testing for Lynch Syndrome. […] If you have been diagnosed with colorectal or endometrial cancer yourself especially below the age of 50 then your doctor may also advise testing for Lynch Syndrome. European guidelines recommend that all patients with colorectal cancer are tested for Lynch Syndrome. […] The type of tests you will undergo for Lynch Syndrome will depend on whether you have already been diagnosed with cancer.

• #68 LYNCP – Overview: Lynch Syndrome Panel, Varies

  https://www.mayocliniclabs.com/test-catalog/Overview/614572

  If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals. […] Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. […] This test is not designed to detect low levels of mosaicism or differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

• #69 How Should We Test for Lynch Syndrome? A Review of Current Guidelines and Future Strategies

  https://www.mdpi.com/2072-6694/13/3/406

  These guidelines are based on decades of evidence that show molecular tumour analysis is a superior screening strategy to select CRC patients for germline MMR gene testing compared to screening by familial or clinical criteria. […] The implementation of LS screening in clinical practice has had mixed efficacy. […] Given these observations, here, we review the key barriers to implementation, as well as the limitations, of current LS screening guidelines. […] A US survey of 509 clinicians belonging to the American College of Gastroenterology found that the most common reasons given for a lack of MMR deficiency testing of CRCs to screen for LS were: prohibitive cost (33.3%), unfamiliarity interpreting results (29.2%), unavailable genetic counselling (24.9%), and unavailable germline genetic testing (20.0%).

• #70 LYNCP – Overview: Lynch Syndrome Panel, Varies

  https://www.mayocliniclabs.com/test-catalog/Overview/614572

  Establishing a diagnosis of Lynch syndrome or constitutional mismatch repair deficiency allowing for targeted cancer surveillance based on associated risks […] Identifying MLH1, MSH2, MSH6, PMS2, or EPCAM variants to allow for predictive testing in family members […] Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for Lynch syndrome. […] First-tier testing may be considered/recommended. […] Testing minors for adult-onset predisposition syndromes is discouraged by the American Academy of Pediatrics, the American College of Medical Genetics and Genomics, and the National Society of Genetic Counselors. […] Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

• #71 Lynch Syndrome – bridging the gap between testing and diagnosis

  https://nonacus.com/blog-lynch-syndrome-testing/

  Unfortunately, 95% of people with Lynch Syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, are unaware they have a pre-disposition to different cancer types. […] Current predictive testing strategies for Lynch Syndrome focus on variant detection within in the mismatch repair genes MLH1, MSH2, MSH6, PMS2 and EPCAM. […] Consequently, turn-around times, and costs, are increased when multiple pathways are required, but there is a next generation sequencing (NGS) single-test solution for Lynch Syndrome screening. […] As part of their routine hereditary cancer screening workflow WMRGL analyzed these samples for variants in MLH1, MSH2, MSH6 and PMS2. Comparing their data, against the results from GALEAS Hereditary Plus, 100% concordance was observed confirming how robust and dependable this NGS assay is as a diagnostic tool for Lynch Syndrome.

• #72 Lynch Syndrome – bridging the gap between testing and diagnosis

  https://nonacus.com/blog-lynch-syndrome-testing/

  Multiplex testing strategies for Lynch Syndrome can be brought together in one workflow by implementing GALEAS Hereditary Plus, reducing pressure on your time and resources. […] To support commitments towards cancer prevention targets GALEAS Hereditary Plus provides a cost effective, single genetic testing solution, with data analysis, for diagnosing Lynch Syndrome, alongside other hereditary cancers.

• #73 Lynch Syndrome Testing & Diagnosis For Providers

  https://lynsightlabs.com/for-providers/

  Early detection is key to effectively managing Lynch syndrome and reducing the risk of associated cancers. By utilizing DiagMMR testing, healthcare providers can identify at-risk individuals early on, allowing for timely intervention, proactive surveillance and personalized risk management strategies. […] DiagMMR represents a significant advancement in Lynch syndrome diagnostics, offering healthcare providers a powerful tool to improve patient care and outcomes. By harnessing the precision and accuracy of DiagMMR, healthcare providers can identify at-risk individuals, implement preventive measures, and ultimately, save lives. […] DiagMMR is a functional test designed to detect mismatch repair (MMR) deficiency from a minimally invasive, non-malignant tissue sample – before tumors appear. Unlike traditional methods, DiagMMR testing is performed directly on patient cells, allowing for accurate detection without the need to know the underlying variant.

• #74 Diagnosing Lynch Syndrome – Irish Medical Journal

  https://imj.ie/diagnosing-lynch-syndrome/

  There is a systematic approach to diagnosing LS. […] Once a personal and family history of cancer meets the Amsterdam II and/or Bethesda criteria, the tumour should be tested for a deficiency of the MMR proteins by immunohistochemistry (IHC), or alternatively for MSI by PCR. […] Then if the MSH2 and MSH6 MMR proteins are deficient by IHC, the patient should proceed to genetic testing. […] Genetic sequencing techniques are then used to confirm the germline mutation in the DNA MMR gene identified by IHC testing. […] Irelands small population offers an opportunity to identify all those with Lynch Syndrome (LS) in the country. […] Screening all colorectal cancers with IHC testing, and/or MSI testing, is being introduced nationally. […] The molecular testing described is relatively inexpensive, especially compared with the costs of managing cancer. […] Lynch Syndrome is underdiagnosed in Ireland. […] Identification of genetic predisposition to Lynch syndrome associated malignancies in a healthy population offers a powerful cancer prevention opportunity. […] Accurate Lynch Syndrome diagnosis would provide a useful pilot for such an initiative.

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