382 hot topic(s) found with the query "Lynch syndrome"
Influence of family history on penetrance of hereditary cancers in a population setting.
Leigh Jackson et al. EClinicalMedicine 2023 11 102159
(Posted: Nov 14, 2023 8AM)
From the abstract: "Women with a pathogenic BRCA1 or BRCA2 variant had an increased risk of breast cancer that was higher in those with a first-degree family history (relative hazard 10.3 and 7.8, respectively) than those without (7.2 and 4.7). Penetrance to age 60 was also higher in those with a family history (44.7%, CI 32.2-59.3 and 24.1%, CI 17.5-32.6) versus those without (22.8%, CI 15.9-32.0 and 17.9%, CI 13.8-23.0). A similar pattern was seen in Lynch syndrome: individuals with a pathogenic MLH1, MSH2 or MSH6 variant had an increased risk of colorectal cancer that was significantly higher in those with a family history (relative hazard 35.6, 48.0 and 9.9) "
Combined population genomic screening for three high-risk conditions in Australia: a modelling study
P Lacaze et al, e Clin Medicine, November 2023
(Posted: Nov 11, 2023 4PM)
From the abstract: "This modeling study assessed the impact of offering combined genomic screening for hereditary breast and ovarian cancer, Lynch syndrome and familial hypercholesterolaemia to all young adults in Australia, compared with the current practice of clinical criteria-based testing for each condition separately. Our findings suggest that offering combined genomic screening for high-risk conditions to young adults would be cost-effective in the Australian public healthcare system, at currently realistic testing costs. "
Neoplasia risk in patients with Lynch syndrome treated with immune checkpoint blockade.
Emily C Harrold et al. Nat Med 2023 10 (10) 2458-2463
(Posted: Oct 19, 2023 2PM)
From the abstract: "Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received =1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21?months (interquartile range, 6–38). "
Public attitudes challenge clinical practice on genetic risk disclosure in favour of healthcare-provided direct dissemination to relatives
A Rosen et al, EJHG, July 20, 2023
(Posted: Jul 20, 2023 7AM)
Germline genetic testing often has implications not only for the individual patient but also for their genetic relatives. This is especially true for high-penetrance pathogenic variants associated with conditions such as familial hypercholesterolemia and hereditary cancer risk syndromes like Lynch syndrome and the hereditary breast and ovarian cancer syndrome. For these conditions, targeted prevention programs are available, and cascade screening is cost-effective. It is therefore highly relevant to find effective strategies to disclose information from the genetic investigation to healthy relatives at risk. Informing relatives at risk enables equitable access to pre-test genetic counselling and a possibility for them to make an informed decision about genetic testing as well as prevention.
The English National Lynch Syndrome Transformation Project
Brit Soc Gastro, July 14, 2023
(Posted: Jul 16, 2023 9AM)
Lynch syndrome (LS) affects approximately 1 in 400 individuals and predisposes to multiple cancers including colorectal, endometrial, gastric, small bowel, cholangiocarinoma and other tumors. Although a common condition, it is estimated that only 5% of patients with LS are known in the UK. There is consistent evidence of the cost-effectiveness and clinical benefit of a structured diagnostic pathway in patients with LS following a diagnosis of cancer linked to cascade testing in families. NICE DG27 and DG42 guidelines recommend universal testing of newly diagnosed colorectal and endometrial cancer for Lynch syndrome (LS), however there is strong evidence of variation in delivery of these guidelines by clinical services.
The Promise of Population-based Genomic Screening for Selected Hereditary Conditions: Contributions of Cost-Effectiveness Analysis
ND Rao et al, CDC Blog Post, July 14, 2023
(Posted: Jul 14, 2023 1PM)
Initial cost-effectiveness research suggests that simultaneous population genomic screening for three CDC Tier 1 genomic applications (hereditary breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia) can be cost effective and reduce morbidity and mortality if implemented in adults younger than 40 years old, costs of screening tests are low, and those found carrying a pathogenic variant have access to preventive care.
Summary for Patients: Population Genomic Screening for Three Common Hereditary Conditions.
et al. Ann Intern Med 2023 5 (5) I19
(Posted: Jun 02, 2023 9AM)
Patients who have certain genetic test results are at higher risk for diseases that may be preventable. There is ongoing debate about whether physicians should screen for 3 hereditary conditions: Lynch syndrome (at greater risk for colon cancer), hereditary breast and ovarian cancer, and familial hypercholesterolemia (at greater risk for early heart disease and stroke). This modeling study found that screening for these 3 hereditary conditions is likely cost-effective in U.S. adults younger than 40 years if the testing cost is relatively inexpensive and people have access to preventive care.
Screening for 3 Genetic Conditions Is Cost-effective in Younger People.
Emily Harris et al. JAMA 2023 5
(Posted: May 24, 2023 9AM)
One-time screening of young adults for 3 conditions—Lynch syndrome, hereditary breast and ovarian syndrome, and familial hypercholesterolemia—would likely be cost-effective compared with only testing patients deemed “high-risk” because of their family histories, according to an analysis of hypothetical cohorts of 100?000 people aged 20 to 60 years. Based on the accepted guideline that interventions priced at no more than $100?000 per quality-adjusted life-year are cost-effective, screening a 30- or 40-year-old person would be worthwhile if the test cost less than $413 or $290, respectively. Assuming a genetic test cost of $250, screening 50-year-old patients would not be cost-effective.
Population Genomic Screening for Three Common Hereditary Conditions : A Cost-Effectiveness Analysis.
Gregory F Guzauskas et al. Ann Intern Med 2023 5
(Posted: May 09, 2023 5AM)
The cost-effectiveness of screening the U.S. population for Centers for Disease Control and Prevention (CDC) Tier 1 genomic conditions is unknown.
We estimated the cost-effectiveness of simultaneous genomic screening for Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), and familial hypercholesterolemia (FH). We found that population genomic screening with a restricted panel of high-evidence genes is likely to be cost-effective in U.S. adults younger than 40 years if the testing cost is relatively low and probands have access to preventive interventions.
The "Scope" of Colorectal Cancer Screening in Lynch Syndrome: Is There an Optimal Interval?
Leah H Biller et al. J Natl Cancer Inst 2023 5
(Posted: May 05, 2023 9AM)
Across all genes related to Lynch syndrome, colonoscopy screening reduces the risk of CRC and improves overall survival among LS carriers, and remains the mainstay of current risk reduction recommendations. What remains less clear are both the optimal age at which to start screening and the best interval
between colonoscopy screenings for LS carriers, such that many international professional society guidelines vary with respect to these recommendations.
Coordinated prospective follow-up of Lynch syndrome is able to detect the majority of incident cancers
P Lafeuille et al, Dig and Liv Dis, April 23, 2023
(Posted: Apr 25, 2023 6AM)
Lynch syndrome: influence of additional susceptibility variants on cancer risk
R Vibert et al, EJHG, April 24, 2023
(Posted: Apr 24, 2023 6AM)
Patterns of care and outcomes of risk reducing surgery in women with pathogenic variants in non-BRCA and Lynch syndrome ovarian cancer susceptibility genes.
Zachary P Schwartz et al. Gynecol Oncol 2023 4 1-7
(Posted: Apr 12, 2023 9AM)
Microsatellite instability in non-colorectal and non-endometrial malignancies in patients with Lynch syndrome.
Lisa Elze et al. Journal of the National Cancer Institute 2023 4
(Posted: Apr 09, 2023 7AM)
In individuals with Lynch syndrome MSI-H/dMMR occurs in more than half of the malignancies other than colorectal and endometrial carcinomas including tumor types without increased incidence. The Lynch-spectrum tumors should be expanded to breast carcinomas with medullary features. All malignancies in patients with Lynch syndrome, independent of subtype, should be tested for MSI-H/dMMR in case therapy with immune checkpoint inhibitors is considered.
Evaluating Colonoscopy Screening Intervals in Patients with Lynch Syndrome from a Large Canadian Registry
M Aronson et al, JNCI, March 25, 2023
(Posted: Mar 25, 2023 8AM)
Lynch Syndrome (LS) screening guidelines originally recommended colonoscopy every 1 to 2 years, beginning between the ages of 20-25 years. Recent studies have questioned the benefits of these short screening intervals in preventing colorectal cancer (CRC). A total of 429 patients with LS were identified with median follow-up of 9.2 years, 44 developed CRC. We found a positive trend between shorter screening intervals and the number of adenomas detected during colonoscopy. Any new adenoma detected at screening decreased 10-year CRC incidence by 11.3%. For MLH1 carriers, a screening interval of 1-2 years vs. 2-3 years led to a 20-year cumulative CRC risk reduction of 28% and 14% in females and males.
Mortality by age, gene and gender in carriers of pathogenic mismatch repair gene variants receiving surveillance for early cancer diagnosis and treatment: a report from the prospective Lynch syndrome database
MD Valentin et al, EClinicalMedicine, March 2023
(Posted: Mar 22, 2023 7AM)
The Prospective Lynch Syndrome Database (PLSD) collates information on carriers of pathogenic or likely pathogenic MMR variants (path_MMR) who are receiving medical follow-up, including colonoscopy surveillance, which aims to the achieve early diagnosis and treatment of cancers. In path_MMR carriers undergoing colonoscopy surveillance, non-colorectal Lynch syndrome cancers were associated with more deaths than were colorectal cancers. Reducing deaths from non-colorectal cancers presents a key challenge in contemporary medical care in Lynch syndrome.
A common cancer at an uncommon age.
Marios Giannakis et al. Science (New York, N.Y.) 2023 3 (6637) 1088-1090
(Posted: Mar 21, 2023 8AM)
Patients with EOCRC have a higher relative prevalence of inherited predisposition to cancer, with Lynch syndrome being the most common cause. This condition is characterized by deficiency in the DNA mismatch repair pathway that results in high levels of microsatellite instability with an increased number of mutations, which predisposes to CRC and other types of cancer. Although underdiagnosis of Lynch syndrome cases may be a potential contributing factor, this and other high-penetrance pathogenic germline variants do not explain the observed rise of EOCRC.
Implementing digital systems to facilitate genetic testing for hereditary cancer syndromes: An observational study of four clinical workflows
C Wang et al, Genetics in Medicine, February 10, 2023
(Posted: Feb 11, 2023 0PM)
This study examined the uptake of genetic counseling and testing following the use of a digital cancer genetic risk assessment program, implemented at 27 health care sites in 10 States using one of four clinical workflows: 1) traditional referral, 2) point-of-care scheduling (POC-S), 3) point-of care counseling/telegenetics (POC-C), and 4) point-of-care testing (POC-T). In 2019, 102,542 patients were screened and 33,113 (32%) were identified as high risk and meeting National Comprehensive Cancer Network (NCCN) genetic testing criteria for Hereditary Breast and Ovarian Cancer, Lynch syndrome or both. Among those identified at high risk, 5147 (16%) proceeded with genetic testing. Genetic counseling uptake was 11% among sites with workflows that included seeing a genetic counselor prior to testing.
Gimme Shelter from Lynch Syndrome
G Hurst, Cure, February 8, 2023
(Posted: Feb 09, 2023 11AM)
Lynch syndrome is not rare — 1 in 280 people have it in the United States, according to the American Cancer Society, and sadly, many of those with it don’t know it. Lynch syndrome is autosomal dominant, meaning a child who has a parent with the mutated gene has a 50% chance of inheriting that mutated gene. I inherited it from my father; now, I cannot help but be worried if my son has it.
Germline mismatch repair (MMR) gene analyses from English NHS regional molecular genomics laboratories 1996-2020: development of a national resource of patient-level genomics laboratory records.
Loong Lucy et al. Journal of medical genetics 2022 12
(Posted: Jan 04, 2023 6AM)
Comparison of Germline Genetic Testing Before and After a Medical Policy Covering Universal Testing Among Patients With Colorectal Cancer
C Moretz et al, JAMA Network Open, October 24, 2022
(Posted: Oct 24, 2022 0PM)
In a cohort study of 9066 patients with CRC in 2017 to 2020, 2288 (25.2%) did not receive MSI/IHC despite being eligible for coverage. In a cohort of 55?595 patients with CRC diagnosed in 2020 and covered by insurance, 1675 (3.0%) received GGT, and 1 in 6 patients had variants that were clinically actionable.
These results indicate that medical policies that provide universal testing for MSI/IHC tumor screening and GGT were underused for patients with CRC, potentially impeding their access to precision therapy, clinical trials, and evidence-based clinical management.
Relatives from Hereditary Breast and Ovarian Cancer and Lynch Syndrome Families Forgoing Genetic Testing: Findings from the Swiss CASCADE Cohort
M Sarki et al, J Per Med, October 19, 2022
(Posted: Oct 20, 2022 8AM)
Among n = 115 relatives who completed the baseline survey, 38% (n = 44) were in the GT (-) group. Being male (OR: 2.79, 95% CI: 1.10–7.10) and without a previous cancer diagnosis (OR: 4.47, 95% CI: 1.03–19.42) increased the odds of being untested by almost three times. Individuals from families with fewer tested relatives had 29% higher odds of being untested (OR: 0.71, 95% CI: 0.55–0.92). Reasons for forgoing cascade testing were lack of provider recommendation, lack of time and interest in testing, being afraid of discrimination, and high out-of-pocket costs.
Proband-mediated interventions to increase disclosure of genetic risk in families with a BRCA or Lynch syndrome condition: a systematic review
AL Young et al, EJHG, October 17, 2022
(Posted: Oct 17, 2022 7AM)
Intervention delivery modes included genetic counselling with additional telephone or in-person follow-up, letters, videos, and decision aids. The percentages of at-risk relatives informed by the proband about their risk ranged from 54.0% to 95.5% in the intervention or family-mediated comparison group. Of those who were informed, 24.4–60.0% contacted a genetics clinic and 22.8–76.2% had genetic testing after they were counselled at a genetics clinic.
Genetic Testing Challenges in Oncology: Lynch Syndrome Diagnosis Despite Negative Test Results
T Ray, Precision Oncology News, August 29, 2022
(Posted: Aug 30, 2022 9AM)
Current screening guidelines recommend that patients between ages 45 and 75 and at average risk for colon cancer, should have colonoscopies every 10 years. However, patients with a personal or family history of colorectal cancer or colon polyps, or patients with Lynch or another inherited cancer syndrome associated with heightened colon cancer risk, may be eligible for more frequent screenings.
Bowel cancer: what role do our genes play?
Genetics Education Program, August 19, 2022
(Posted: Aug 21, 2022 3PM)
A person’s risk of developing colorectal cancer is influenced by lifestyle factors, such as a low-fiber diet and lack of regular physical activity; however, as is the case with breast cancer, some inherited genetic variants increase the likelihood of a person developing colorectal cancer. In this article, we look at two genetically inherited syndromes and examine how and why they increase a person’s risk of this particular cancer.
Risk factors for gastric cancer in patients with Lynch syndrome.
Ortigão Raquel et al. European journal of gastroenterology & hepatology 2022 7
(Posted: Jul 20, 2022 7AM)
Incomplete Penetrance of Population-Based Genetic Screening Results in Electronic Health Record
G Elhanan et al, Frontiers in Genetics, April 2022
(Posted: May 26, 2022 7AM)
The clinical value of population-based genetic screening projects depends on the actions taken on the findings. The Healthy Nevada Project (HNP) is an all-comer genetic screening and research project based in northern Nevada. HNP participants with CDC Tier 1 findings of hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), or familial hypercholesterolemia (FH) are notified and provided with genetic counseling. However, the HNP subsequently takes a “hands-off” approach: it is the responsibility of notified participants to share their findings with their healthcare providers, and providers are expected to implement the recommended action plans.
Paired Tumor-Germline Testing as a Driver in Better Cancer Care
JW Henson et al, JAMA Network Open, May 20, 2022
(Posted: May 21, 2022 2PM)
Paired tumor-germline testing can lead to better treatment choices. Hereditary cancer syndromes are caused by inactivated tumor suppressor genes. By comparison, activated oncogenes are poorly tolerated during embryonic development. Variant tumor suppressor genes and their inactive protein products are more challenging to target than are activated oncogenes. Attention thus turns from the gene itself to the aberrant downstream molecular pathway and subsequent effects of the pathway. Two notable examples are the use of checkpoint inhibitors to target high tumor mutation burdens from tumors related to a defective mismatch repair pathway (ie, Lynch syndrome when originating in germline) and poly adenosine diphosphate ribose polymerase inhibitors to exploit single-strand breaks from tumors related to the homologous repair/BRCA pathway (ie, hereditary breast and ovarian cancer syndrome when originating in germline).
Lynch syndrome; towards more personalized management?
J Llach et al, Best Practice & Research Clinical Gastroenterology, March 2022
(Posted: Apr 20, 2022 9AM)
Lynch syndrome is the most common inherited cause of colorectal (lifetime risk up to 70%) and endometrial cancer. The diagnosis of Lynch syndrome facilitates preventive measures aimed at reducing the incidence and mortality of cancer. Colonoscopic surveillance for colorectal cancer, aspirin, and prophylactic hysterectomy and bilateral salpo-oopherectomy for endometrial and/or ovarian cancer have demonstrated to effectively reduce cancer mortality in this population. However, the lifetime risk of each cancer in people with Lynch syndrome is gene-specific and may be modified by environmental factors. Furthermore, the benefits of surveillance strategies need to be balanced against the risk of over-diagnosis and be supported by evidence of improved outcomes
New generation of cancer-preventing vaccines could wipe out tumors before they form
J Kaiser, Science, April 7, 2022
(Posted: Apr 09, 2022 1PM)
Researchers are trying out several vaccine strategies. Some use so-called tumor antigens, molecular markers that are scarce on healthy cells but plentiful on cancer cells. The Lynch syndrome vaccine instead targets “neoantigens,” a potent type of antigen only found on tumor cells. Some deploy just a single antigen whereas others use a large number, in a bid to broadly shield against cancer. The best approach is unclear, and developers also face the difficult challenge of measuring success without waiting decades for healthy people to develop cancers.
Cost-effectiveness of population-wide genomic screening for Lynch syndrome in the United States.
Guzauskas Gregory F et al. Genetics in medicine : official journal of the American College of Medical Genetics 2022
(Posted: Mar 05, 2022 7AM)
We developed a decision-analytic Markov model including health states for precancer, stage-specific CRC, and death and assumed an inexpensive test cost of $200. We conducted sensitivity and threshold analyses to evaluate model uncertainty. Population LS screening may be cost-effective in younger patient populations under a $150,000 willingness-to-pay per QALY threshold and with a relatively inexpensive test cost. Further reductions in testing costs and/or the inclusion of LS testing within a broader multiplex screening panel are needed for screening to become highly cost-effective.
FORCE, February 2022
(Posted: Feb 20, 2022 7AM)
If you have been diagnosed with Lynch syndrome, you have may questions about your medical care. This page has information on cancer risk, screening, prevention and treatment for people with an inherited mutation in a Lynch syndrome gene. We've compiled expert-reviewed resources to help you take steps to protect your own health and the health of your relatives. Click on each topic below to learn more. If you need additional guidance, please sign up for our Peer Navigation Program. You are not alone.
Lynch Syndrome: A Common Yet Under-Recognized Hereditary Cancer Predisposition
Lynch Syndrome Ireland, February 1, 2022
(Posted: Feb 01, 2022 7AM)
Lynch syndrome is the most common inherited predisposition to colorectal and endometrial (uterine) cancers, yet is it under-diagnosed. Around 90-95% of people who have Lynch syndrome are not aware of their condition. This is a major concern because many of the cancers associated with Lynch syndrome are preventable or could be detected earlier through intensive cancer surveillance. Identifying patients with Lynch syndrome also helps with testing other members of their family who may be at risk.
A Mini-Symposium: Implementing Precision and Equitable Public Health in Cascade Testing for Genetic Disorders
CDC event, Feb 10, 2022
(Posted: Dec 13, 2021 2PM)
While there are Tier 1 evidence-based guidelines supporting cascade testing for hereditary breast and ovarian cancer syndrome, Lynch syndrome, familial hypercholesterolemia, and other genetic disorders, the focus is on whether such testing should be done, rather than how to implement cascade testing in practice, both effectively and equitably. Before the full potential health impact of cascade genetic testing can be reached, we must develop a much stronger understanding of which component procedures and practices work best, and then leverage those good practices toward delivering precision public health. This two-hour virtual mini-symposium will explore several efforts to better understand what works well in programs relevant to cascade testing for genetic disorders.
30 year experience of index case identification and outcomes of cascade testing in high-risk breast and colorectal cancer predisposition genes
ER Woodward et al, EJHG, December 6, 2021
(Posted: Dec 06, 2021 6AM)
We recorded 2082 positive index case diagnostic screening tests, generating 3216 positive and 3140 negative family cascade (non-index) tests. This is equivalent to an average of 3.05 subsequent cascade tests per positive diagnostic index test, with 1.54 positive and 1.51 negative non-index tests per family. The CPGs with the highest numbers of non-index positive cases identified on cascade testing were BRCA1/2 (n?=?1999) and the mismatch repair CPGs associated with Lynch Syndrome (n?=?731).
Up-Front Multigene Panel Testing for Cancer Susceptibility in Patients With Newly Diagnosed Endometrial Cancer: A Multicenter Prospective Study
MD Levine et al, JCO Precision Oncology, October 2021
(Posted: Dec 02, 2021 8AM)
Likely pathogenic variants or PVs were identified in 97 of 961 women (10.1%). Lynch syndrome was diagnosed in 29 of 961 patients (3%; 95% CI, 2.1 to 4.3), with PVs in PMS2 most frequent. MGPT revealed nine patients with LS in addition to the 20 identified through routine tumor-based screening. BRCA1 and BRCA2 PVs were found in 1% (10 of 961; 95% CI, 0.6 to 1.9) of patients and that group was significantly enriched for type II ECs.
Should Children Be Tested for Hereditary Cancer Syndromes?
G Hurst, Cure magazine, November 8, 2021
(Posted: Nov 09, 2021 6AM)
Not all children can handle the emotional toll a Lynch syndrome diagnosis may bring. Genetically testing minor children for hereditary cancer syndromes before they reach adulthood may be more harmful than beneficial because this knowledge is not actionable in childhood.
National Hereditary Cancer Week 2021
FORCE, September 2021
(Posted: Sep 29, 2021 10AM)
National Hereditary Cancer Week is a time to recognize and honor those who have been affected by hereditary cancer. This includes people with Lynch syndrome or an inherited mutation in BRCA1/2, ATM, BRIP1,CHEK2, PALB2, PTEN, RAD51C/D or other gene associated with hereditary cancer. It is also an opportunity to acknowledge hereditary cancer survivors, previvors, caregivers and their families.
Should women with Lynch syndrome be offered gynaecological cancer surveillance?
NAJ Ryan, BMJ, September 2, 2021
(Posted: Sep 03, 2021 7AM)
Lynch syndrome is an inherited genetic condition associated with an increased risk of endometrial and ovarian cancer in women. Limited low quality evidence from observational studies show that gynaecological surveillance detects cancers in women with Lynch syndrome; but it is uncertain if this improves survival, and the optimal testing strategy is not established. Inform women with Lynch syndrome about their risk of developing cancer and initiate a discussion about their preference for risk reducing surgery which is definitive, or options for annual review and gynaecological surveillance, explaining their risks and benefits.
Health Equity and Genetic Disorders
CDC, August 2021
(Posted: Sep 01, 2021 7AM)
Public health efforts to achieve health equity need to include people with genetic disorders. Thousands of inherited genetic disorders affect millions of people in the United States. Genetic disorders include both single-gene disorders, such as cystic fibrosis and sickle cell disease, and conditions that make people more likely to develop common chronic diseases, such as hereditary breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia.
Living with Lynch Syndrome: Pick Your Hard
G Hurst, Cure, August 31, 2021
(Posted: Sep 01, 2021 7AM)
Women with hereditary cancer syndromes must make difficult decisions. This year marks a decade since I underwent prophylactic surgeries to reduce my cancer risks to my reproductive organs for Lynch syndrome. I did not understand how influential and impactful estrogen was for my well-being and health until my ovaries were removed. Many fail to recognize that estrogen is necessary to help your body and its parts work in concert with each other seamlessly.
PMS2 is the most frequently mutated Lynch syndrome (LS) gene in women with endometrial cancer (EC): what is the role that low penetrance LS genes play in EC?
M Levine et al, Obs Gyn, August 2021
(Posted: Aug 22, 2021 7AM)
This is the largest cohort of prospectively enrolled EC patients to undergo germline genetic testing in an unselected manner, irrespective of patient age, family history or tumor results. It shows that a majority of LS mutations in EC are in the low-penetrance genes, MSH6 and PMS2. PMS2 mutations were the most common.
Vaccine to Prevent Hereditary Cancers Nears Human Trials
S Jenks, NCI Blog, July 2021
(Posted: Jul 18, 2021 7AM)
One of the first-ever vaccines for the prevention of colorectal and other cancers in patients at high genetic risk for these malignancies is expected to start its early phase safety and immunogenicity trial in the first quarter of 2022, according to investigators. Although still in the design phase, the study will test a neoantigen-based vaccine against Lynch syndrome, a common hereditary condition that carries a 70-80% lifetime risk for colorectal cancer. The syndrome also raises the risk for developing endometrial cancer and several other cancers, often before age 50 years.
Prospective Statewide Study of Universal Screening for Hereditary Colorectal Cancer: The Ohio Colorectal Cancer Prevention Initiative.
Pearlman Rachel et al. JCO precision oncology 2021 7
(Posted: Jul 14, 2021 6AM)
Three thousand three hundred ten unselected adults who underwent surgical resection for primary invasive CRC were prospectively accrued from 51 hospitals across Ohio between January 1, 2013, and December 31, 2016. Universal Tumor screening (UTS) for mismatch repair (MMR) deficiency was performed for all. UTS alone is insufficient for identifying a large proportion of CRC patients with hereditary syndromes, including some with LS. At a minimum, 7.1% of individuals with CRC have a PGV and pan-cancer MGPT should be considered for all patients with CRC.
Expanding Germline Testing to All Patients With Esophagogastric Cancers—Easy to Do, Harder to Justify
JAMA Network Open, July 12, 2021
(Posted: Jul 13, 2021 7AM)
Guidelines currently support disease site–specific testing of patients with colorectal cancer younger than 50 years and all patients with pancreatic cancer. Testing patients with esophagogastric cancer (EGC), however, currently requires a known familial variant or a strong personal or family history indicative of a hereditary cancer syndrome, such as hereditary diffuse gastric cancer or Lynch syndrome.
Primary care providers’ responses to unsolicited Lynch syndrome secondary findings of varying clinical significance
LN Galbraith et al, Genet in Med, June 10, 2021
(Posted: Jun 11, 2021 7AM)
We randomized 148 American Academy of Family Physicians members to review three reports with varying significance for Lynch syndrome. Participants provided open-ended responses about the follow-up they would address and organized the SF reports and five other topics in the order they would prioritize responding to them (1?=?highest priority, 6?=?lowest priority). Results suggest that while PCPs appreciated the differences in clinical significance, disclosure of VUS as SFs would substantially increase downstream health-care utilization.
Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study
The International Mismatch Repair Consortium, The Lancet Oncology, June 7, 2021
(Posted: Jun 09, 2021 7AM)
Familial risk factors result in a wide within-gene variation in the risk of colorectal cancer for men and women from each continent who all carried pathogenic variants in the same gene or the MSH2 c.942+3A>T variant. The variation was especially prominent for MLH1 and MSH2 variant carriers, depending on gene, sex and continent, with 7–56% of carriers having a colorectal cancer penetrance of less than 20%, 9–44% having a penetrance of more than 80%, and only 10–19% having a penetrance of 40–60%.
Stakeholders’ views of integrating universal tumour screening and genetic testing for colorectal and endometrial cancer into routine oncology
ER O'Shea et al, JHG, April 2021
(Posted: Apr 03, 2021 7AM)
The majority of respondents saw the relative advantage of aligning GT to abnormal universal tumor screening (UTS) results.
Both OHP and GHP’s indicated embedding a genetic counsellor in oncology or having a genetics point of contact to support integrating of GT through UTS as favorable interventions. I
Interventions Facilitating Family Communication of Genetic Testing Results and Cascade Screening in Hereditary Breast/Ovarian Cancer or Lynch Syndrome: A Systematic Review and Meta-Analysis.
Baroutsou Vasiliki et al. Cancers 2021 13(4)
(Posted: Mar 09, 2021 9AM)
The study identified interventions designed to facilitate family communication of genetic testing results and/or cancer predisposition cascade genetic testing for HBOC and LS. We conducted a systematic review and meta-analysis of randomized trials that assessed intervention efficacy for these two outcomes. Additional outcomes were also recorded and synthesized when possible. 14 articles met the inclusion criteria and were included in the narrative synthesis.
Room for improvement: One third of Lynch syndrome patients presenting for genetic testing in a highly specialised centre in Stockholm already have cancer.
Bernstedt Sophie Walton et al. Hereditary cancer in clinical practice 2021 Feb 19(1) 18
(Posted: Feb 16, 2021 9AM)
Three major reasons for diagnosis were identified: 1. Predictive testing of a previously known mutation in the family (62%, mean age 37), 2. A family history of Lynch associated tumors (9%, mean age 37), 3. A diagnosis of cancer (29%, mean age 51). The proportion diagnosed due to cancer has not changed over time. A high proportion of patients (29%) were identified with Lynch syndrome after they had been diagnosed with an associated cancer.
New Technique Identifies Important Mutations Behind Lynch Syndrome - Approach could improve predictive value of genetic screening.
K Malcom, University of Michigan, January 27, 2021
(Posted: Jan 29, 2021 8AM)
Acquired somatic MMR deficiency is a major cause of MSI tumor in patients suspected for “Lynch-like syndrome” including young patients
S Lefol et al, EJHG, December 5, 2020
(Posted: Dec 07, 2020 8AM)
Patients with tumors displaying high microsatellite instability (MSI-H) but no germline MMR inactivation are suspected for Lynch-like syndrome (LLS). We screened 113 patient tumor samples for MMR gene variations and loss of heterozygosity. Somatic MMR alterations were found in 85.8% of patients including “double hits” in 63.7% of patients, mainly diagnosed with colon and endometrial cancers. Interestingly, 37.5% of them were under the age of 50, and seven patients were under 30.
Pembrolizumab in MSI-H–dMMR Advanced Colorectal Cancer — A New Standard of Care
A Grothey, NEJM, December 2, 2020
(Posted: Dec 03, 2020 7AM)
Germline mutations in genes encoding mismatch repair proteins are hallmarks of Lynch syndrome, but the deficient mismatch repair (dMMR) phenotype is commonly found in sporadic, nonfamilial cancers. The phenotype itself leads to a high degree of microsatellite instability (MSI-H), which is assessed with the use of polymerase chain reaction or next-generation sequencing. MSI-H–dMMR cancers have been recognized to be sensitive to treatment with immune checkpoint inhibitors.
Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report
MD Valentin et al, Genetics in Medicine, December 1, 2020
(Posted: Dec 01, 2020 8AM)
The Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.
Lu Karen H et al. The New England journal of medicine 2020 Nov (21) 2053-2064
(Posted: Nov 20, 2020 8AM)
Identification of the Lynch syndrome in patients with endometrial cancer has become increasingly important, since immune checkpoint blockade has been approved for the treatment of advanced disease with high microsatellite instability. Another factor favoring identification of patients with the Lynch syndrome is that they are at increased risk for colon cancer.
Testing strategies for Lynch syndrome in people with endometrial cancer
NICE, October 28, 2020
(Posted: Oct 28, 2020 9AM)
Offer testing for Lynch syndrome to people who are diagnosed with endometrial cancer. Use immunohistochemistry (IHC) to identify tumors with mismatch repair (MMR) deficiency. Healthcare professionals should inform people about the possible implications of test results for both themselves and their relatives, and give support and information. Discussion of genetic testing and obtaining consent should be done by a healthcare professional with appropriate training.
Germline Testing for Lynch Syndrome: More Important Than Ever
B Cote, Onc Nursing News, October 2020
(Posted: Oct 12, 2020 7AM)
With the emergence of several targeted treatments that have shown efficacy in individuals with germline pathogenic variants, specifically in DNA mismatch repair, the need for germline genetic testing has become even more pronounced.
Diagnostics of Mutations in MMR/EPCAM Genes and Their Role in the Treatment and Care of Patients with Lynch Syndrome
J Sobocinka et al, MDPI Diagnostics, October 2020
(Posted: Oct 12, 2020 7AM)
In this review, the mutations involved with LS and their diagnostic methods are described and compared, as are their current uses in clinical decision making. LS diagnosis is based on a review of family medical history, and when necessary, microsatellite instability (MSI) or/and immunohistochemistry (IHC) analyses. In the case of a lack of MMR protein expression (dMMR) or MSI-H (MSI-High) detection in tumor tissue, molecular genetic testing can be undertaken.
Implementing Cancer Genomics in State Health Agencies: Mapping Activities to an Implementation Science Outcome Framework.
Green Ridgely Fisk et al. Public health genomics 2020 Sep 1-12
(Posted: Sep 18, 2020 9AM)
We identified state health agency activities addressing hereditary breast and ovarian cancer and Lynch syndrome by reviewing project narratives from Centers for Disease Control and Prevention Cancer Genomics Program funding recipients, leading discussions with state health agencies, and conducting an environmental scan.
Refining risk-estimates in HNPCC: are we there yet?
PM ynch et al, JNCI Cancer Spectrum, 2020
(Posted: Sep 08, 2020 11AM)
LIVING WITH LYNCH 2020- Virtual Patient Workshop
Alive and Kicking and Colon Cancer Foundation Webinar October 9, 2020
(Posted: Aug 21, 2020 9AM)
Join for unique patient perspectives and the latest information from experts on Lynch syndrome.
Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions
AC Fahed et al, Nature Communications, August 20, 2020
(Posted: Aug 21, 2020 9AM)
We study 80,928 individuals to examine whether polygenic background can modify penetrance of disease in tier 1 genomic conditions — familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome. Among carriers of a monogenic risk variant, we estimate substantial gradients in disease risk based on polygenic background — the probability of disease by age 75 years ranged from 17% to 78% for coronary artery disease, 13% to 76% for breast cancer, and 11% to 80% for colon cancer.
Strategies to Identify and Care for Individuals with Inherited Cancer Syndromes
NCI Webinar, July 30, 2020
(Posted: Jul 07, 2020 10AM)
Focused on health care delivery and identifying best practices for case ascertainment and follow-up care in inherited cancer syndromes, NCI seeks to improve sustainable implementation of care delivery models. This webinar discusses the hereditary cancers Cancer Moonshot effort, research and perspective from a current grantee, and directions for future work.
Clinical outcomes of a genomic screening program for actionable genetic conditions
AH Buchanan et al, Genetics in Medicine, June 30, 2020
(Posted: Jul 01, 2020 8AM)
A study of electronic health records shows that among individuals with variants in tier1 genes (BRCA, Lynch syndrome, familial hypercholesterolemia, 87% did not have a prior genetic diagnosis. Genomic screening programs can identify individuals at increased risk of cancer and heart disease and facilitate risk management and early cancer detection.
Aspirin for Lynch syndrome: a legacy of prevention
MB Yurgelun et al, The Lancet, June 13, 2020
(Posted: Jun 13, 2020 7AM)
Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, randomised, placebo-controlled trial
J Burn et al, The Lancet June 13, 2020
(Posted: Jun 13, 2020 7AM)
In the double-blind, randomized CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [<1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment.
Comparison of two Lynch screening strategies in endometrial cancer in a California health system.
Lentz Scott E et al. Gynecologic oncology 2020 May
(Posted: May 12, 2020 4PM)
Adequacy evaluation of the annual colonoscopic surveillance and individual difference of disease phenotypes in Lynch syndrome.
Taniguchi Fumitaka et al. Japanese journal of clinical oncology 2020 May
(Posted: May 12, 2020 4PM)
Association of Rare Pathogenic DNA Variants for Familial Hypercholesterolemia, Hereditary Breast and Ovarian Cancer Syndrome, and Lynch Syndrome With Disease Risk in Adults According to Family History
AP Patel, JAMA Network Open, April 29, 2020
(Posted: Apr 30, 2020 8AM)
In this cohort study of 49?738 participants in the UK Biobank, a pathogenic or likely pathogenic variant associated with the 3 tier 1 genomic conditions (BRCA, Lynch syndrome, FH) was identified in 0.9% of participants. These individuals had an increased risk of disease identified by gene sequencing that was not found through self-reported family history.
Investigating the Link between Lynch Syndrome and Breast Cancer.
Sheehan Megan et al. European journal of breast health 2020 Apr 16(2) 106-109
(Posted: Apr 22, 2020 9AM)
Associations Between Mutations in MSH6 and PMS2 and Risk of Surveillance-detected Colorectal Cancer.
Lamba Mehul et al. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2020 Mar
(Posted: Apr 08, 2020 9AM)
The Prospective Lynch Syndrome Database reports enable evidence-based personal precision health care.
Møller Pål et al. Hereditary cancer in clinical practice 2020 186
(Posted: Mar 25, 2020 9AM)
My genes are stacked against me; it's made me a fighter
A Leippi, CBC News, January 22, 2020
(Posted: Jan 23, 2020 11AM)
Lynch Syndrome gives the carrier a genetic predisposition to several cancers. Knowing what is in my family history has given me two options: either cause me to live in fear or push me to educate myself on what I can do to give me the best chance to live a long life. I personally have chosen option two and used it as a way to help others succeed in their lives.
Celebrating the career and contributions of Dr Henry T. Lynch (1928-2019).
Butel-Simoes Grace I et al. Internal medicine journal 2020 Jan 50(1) 108-109
(Posted: Jan 22, 2020 9AM)
This article celebrates the career of Dr Henry Lynch and his contributions to cancer genetics through his extensive research, clinical practice and his passion for personalising care by using a patient's genetic profile to determine management and treatment. Dr Lynch's contributions were momentous and continue to have relevance to medical practice.
Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome.
Engel Christoph et al. Gastroenterology 2020 Jan
(Posted: Jan 15, 2020 8AM)
Mayo genomic database to use sequencing for 100K participants
G Slabodkin, Health Data Management, January 10, 2020
(Posted: Jan 13, 2020 9AM)
The Mayo Clinic will build a library of genomic sequencing data on 100,000 volunteers, who will be initially screened for three hereditary conditions.Participants in the first part of the study—called Tapestry—will receive screening results for familial hypercholesterolemia, hereditary breast and ovarian cancer (BRCA1 and BRCA2), and Lynch syndrome.
Benefit from extended surveillance interval on colorectal cancer risk in Lynch syndrome.
Lindberg Lars Joachim et al. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland 2019 Dec
(Posted: Jan 02, 2020 10AM)
Extent of Pedigree Required to Screen for and Diagnose Hereditary Nonpolyposis Colorectal Cancer: Comparison of Simplified and Extended Pedigrees.
Heo Yoonjung et al. Diseases of the colon and rectum 2019 Dec
(Posted: Dec 18, 2019 8AM)
Targeted deep-intronic sequencing in a cohort of unexplained cases of suspected Lynch syndrome.
Arnold Anke Marie et al. European journal of human genetics : EJHG 2019 Dec
(Posted: Dec 12, 2019 9AM)
Low Rates of Genetic Counseling and Testing in Individuals at Risk for Lynch Syndrome reported in the National Health Interview Survey.
Faust Nolan et al. Gastroenterology 2019 Dec
(Posted: Dec 11, 2019 9AM)
Implementing universal cancer screening programs can help sustain genomic medicine programs
AK Rahm et al, Frontiers in Genetics, December 2019
(Posted: Dec 11, 2019 7AM)
In this commentary, we discuss how implementing evidence-based universal cancer screening programs, such as universal Lynch syndrome screening and other programs, can sustain current genomic medicine programs and pave the way for future genomic screening programs.
The Current Practice of Lynch Syndrome Diagnosis and Management in Italy: A Qualitative Assessment.
Tognetto Alessia et al. Public health genomics 2019 Dec 1-19
(Posted: Dec 07, 2019 7AM)
Low rates of cascade genetic testing among families with hereditary gynecologic cancer: An opportunity to improve cancer prevention.
Griffin Natalie E et al. Gynecologic oncology 2019 Nov
(Posted: Dec 04, 2019 10AM)
Cascade genetic testing (CGT) of hereditary breast and ovarian cancer (HBOC) or Lynch Syndrome (LS) patients' relatives offers opportunities to prevent cancer, but CGT rates are not well described. We aimed to measure reported disclosure of genetic testing results and CGT rates in these families and evaluate patients' views of educational media.
Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG).
Monahan Kevin J et al. Gut 2019 Nov
(Posted: Dec 04, 2019 9AM)
This guideline is an update from the 2010 guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC.
People with genetic condition should be given aspirin daily to slash their risk of colorectal cancer
Denton Daily, November 24, 2019
(Posted: Nov 25, 2019 8AM)
Thousands of people with a common genetic condition should take aspirin every day to slash their risk of colorectal cancer, health officials rule. In its draft NICE While there are risks associated with long-term aspirin use, the committee agreed that the benefits are likely to outweigh any potential harms.
Guidelines for the management of hereditary colorectal cancer from the BSG /ACPGBI/UKCGG
British Society Gastroenterology, October 2019
(Posted: Nov 10, 2019 8AM)
Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/ Association of Coloproctologists of Great Britain and Ireland (ACPGBI)/ United Kingdom Cancer Genetics Group (UKCGG).
Cost-effectiveness of Active Identification and Subsequent Colonoscopy Surveillance of Lynch Syndrome Cases.
Peterse Elisabeth F P et al. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2019 Oct
(Posted: Oct 23, 2019 9AM)
Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report
MD Valentin et al, Hereditary Cancer in Clinical Practice, October 2019
(Posted: Oct 23, 2019 8AM)
The predicted impact and cost-effectiveness of systematic testing of people with incident colorectal cancer for Lynch syndrome.
Kang Yoon-Jung et al. The Medical journal of Australia 2019 Oct
(Posted: Oct 16, 2019 9AM)
A Patient’s Guide to Endometrial Cancer-This cancer is on the rise. But early detection saves lives.
MO Shroeder, US News, October 4, 2019
(Posted: Oct 05, 2019 9AM)
Risk factors for this cancer include: obesity, diabetes, having close relatives like a parent or sibling who have endometrial cancer or colorectal cancer, and a genetic condition called Lynch syndrome. Having Lynch syndrome greatly increases a woman’s risk of developing endometrial cancer, and other cancers like colon and ovarian cancer
Can an Aspirin a Day Prevent Colorectal Cancer in People with Lynch Syndrome?
S Bowen et al, CDC Blog, October 2, 2019
(Posted: Oct 04, 2019 10AM)
The new NICE draft guidance based on a groundbreaking clinical trial, in review, at the time of this blog, NICE is circulating draft language, based on clinical trials, which essentially states that an aspirin taken daily for more than two years reduces the risk of colorectal cancer among people with Lynch syndrome.
For women Lynch syndrome is about more than colon cancer.
Parker Wendy M et al. Cancer prevention research (Philadelphia, Pa.) 2019 Sep
(Posted: Oct 02, 2019 8AM)
We had the chance to listen to women with LS, in their own words, discuss their health care experiences as they relate to gynecologic cancer risk and identified several important themes. They describe feeling confused about their screening and surveillance options while also being heavily reliant on their health care providers for guidance.
Sir John Burn Delivers Seminar on Prediction and Prevention of Colorectal Cancer in Patients with Lynch Syndrome
NCI,September 26, 2019
(Posted: Sep 28, 2019 8AM)
He presented new insights into the mechanisms and natural history of colorectal cancer associated with Lynch Syndrome and the longitudinal trials on protective effects of aspirin. He also presented efforts to build robust, international, annotated genetic databases.
Implementation science and genomic medicine in action: A case study
M Clyne et al, CDC Blog, September 18, 2019
(Posted: Sep 19, 2019 9AM)
An ideal opportunity to understand how a genomic research activity falls into the implementation science realm is to read through the details of an applicable study. Here, we will guide you through a study on ”Implementing Universal Lynch Syndrome Screening: Identifying Strategies to Facilitate and Maintain Programs in Different Organizational Contexts."
White-light Endoscopy is Adequate for Lynch Syndrome Surveillance in a Randomized and Non-inferiority Study.
Rivero-Sánchez Liseth et al. Gastroenterology 2019 Sep
(Posted: Sep 18, 2019 10AM)
What you need to know about ovarian cancer
(Posted: Sep 05, 2019 8AM)
There is no way to know for sure if you will get ovarian cancer. Most women get it without being at high risk. However, several factors may increase a woman’s risk for ovarian cancer, including if you are middle-aged or older; have close family members who have had ovarian cancer; have a genetic mutation called BRCA1 or BRCA2, or Lynch syndrome.
New Data Reveal that Expanding Genetic Testing Guidelines Could Identify More Patients with Increased Risks of Cancer
A Viejo, PRWeb, August 27, 2019
(Posted: Aug 28, 2019 7AM)
A recent study found that updating the BRCA1 and BRCA2 and Lynch syndrome testing criteria to include more medically actionable, cancer-predisposition genes – and relaxing current criteria, such as age-at-diagnosis constraints – would identify more patients at risk for developing hereditary cancer.
Implementing Universal Lynch Syndrome Screening across Multiple Healthcare Systems: Identifying Strategies to Facilitate and Maintain Programs in Different Organizational Contexts
NCI, August 2019
(Posted: Aug 23, 2019 11AM)
The National Cancer Institute frequently receives requests for examples of funded grant applications. Several investigators and their organizations agreed to let Implementation Science (IS) post excerpts of their dissemination and implementation (D&I) grant applications online.
Rationale for evaluating breast cancers of Lynch syndrome patients for mismatch repair gene expression.
Sorscher Steven et al. Breast cancer research and treatment 2019 Aug
(Posted: Aug 14, 2019 8AM)
A clinical guide to hereditary cancer panel testing: evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients
H LaDuca et al, Genetics in Medicine, August 13, 2019
(Posted: Aug 13, 2019 9AM)
Opportunities to improve upon identification of patients at risk for hereditary cancer predisposition include revising BRCA1/2 and Lynch syndrome testing criteria to include additional clinically actionable genes with overlapping phenotypes and relaxing testing criteria for associated cancers.