Discussions about predictive genetic testing for Lynch syndrome: the role of health professionals and families in decisions to decline

AbstractUnaffected relatives of individuals with Lynch syndrome can be offered predictive genetic testing to guide surveillance recommendations. The decision-making process of those who decline testing, particularly those who do not attend a clinical genetics service, is poorly understood. We have addressed this gap by interviewing 33 individuals from Lynch syndrome mutation-carrying families, unaffected by cancer, who declined predictive genetic testing. Here, we analyse the data provided by 20 participants who unequivocally declined testing. Those who indicated they did not have enough information to make a decision or intended to undergo testing in the future were excluded. Analysis revealed that few decliners discussed their decision with general practitioners or genetic counsellors. Family members were commonly involved to varying degrees, with participants either (1) making group decisions with family members, (2) feeling persuaded by family members to either accept or decline testing, (3) discussing the test but making their own decision. A minority did not discuss testing with family members while making their decision. This research reveals the health communication activities of an understudied group, those declining predictive testing, and indicates that for many, health professionals play a minor role in the decision compared to family.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research

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We report the case of a Lynch syndrome patient with metastatic CRC and urothelial cancer who was treated sequentially with pembrolizumab (targeting PD1), atezolizumab (targeting PD‐L1), brief rechallenge with pembrolizumab, and finally the combination of ipilimumab (targeting CTLA‐4) and nivolumab (targeting PD1). Over a 28‐month period the patient experienced prolonged disease control with each different regimen the first time it was given, including metabolic response by positron emission tomography and computed tomography scanning and tumor marker reductions. The case suggests that some patients with advanced MMR...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Precision Medicine Clinic: Molecular Tumor Board, Gastrointestinal Cancer Precision Medicine Clinic: Molecular Tumor Boards Source Type: research
An estimated 130,000 individuals are diagnosed with colorectal carcinoma each year, and approximately 50,000 will die from this disease, making colorectal carcinoma the third leading cause of cancer deaths in the United States.1 Heritable forms of colorectal carcinoma are common. These heritable conditions may manifest as a polyposis or as colorectal carcinoma. In this review, the pathology of hamartomatous polyps will be discussed with particular emphasis on clues that should alert pathologists to the possibility of a polyposis syndrome.
Source: Diagnostic Histopathology - Category: Pathology Authors: Tags: Mini-symposium: Gastrointestinal/Hepato-Pancreato-Biliary Pathology Source Type: research
Since 2017, the National Institute for Health and Care Excellence (NICE) has recommended molecular testing of all patients with newly diagnosed colorectal cancer (CRC) to identify those with suspected Lynch syndrome who should be referred to clinical genetics for germline testing. The pathway involves firstly determining the mismatch repair (MMR) expression status by immunohistochemistry (IHC) or performing microsatellite instability testing. This may be followed by BRAF V600E mutation testing and then MLH1 promoter hypermethylation analysis depending on the result.
Source: Diagnostic Histopathology - Category: Pathology Authors: Tags: Mini-symposium: Gastrointestinal/Hepato-Pancreato-Biliary Pathology Source Type: research
Defective mismatch repair leads to increased mutation rates, and germline loss-of-function variants in the repair component MLH1 cause the hereditary cancer predisposition disorder known as Lynch syndrome. Early diagnosis is important, but complicated by many variants being of unknown significance. Here we show that a majority of the disease-linked MLH1 variants we studied are present at reduced cellular levels. We show that destabilized MLH1 variants are targeted for chaperone-assisted proteasomal degradation, resulting also in degradation of co-factors PMS1 and PMS2. In silico saturation mutagenesis and computational pre...
Source: eLife - Category: Biomedical Science Tags: Cancer Biology Computational and Systems Biology Source Type: research
CONCLUSION: This is the first audit of a Canadian-based universal LS screening protocol of patients with endometrial cancer. The success of the protocol is endorsed by the 80% compliance and by the 2% prevalence of LS, which is within the published range. PMID: 31679916 [PubMed - as supplied by publisher]
Source: Journal of Obstetrics and Gynaecology Canada : JOGC - Category: OBGYN Tags: J Obstet Gynaecol Can Source Type: research
Conclusions: Our results suggest that transcriptional patterns are indicative for TMM pathway activation with subtle differences between TEL and ALT mechanisms in a CRC subtype-specific fashion. Sequencing data potentially provide a suited measure to study alterations of telomere length and of underlying transcriptional regulation. Further studies are needed to improve this method.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
AbstractPurpose of reviewIdentification of Lynch syndrome is important from an individual patient and public health standpoint. As paradigms for Lynch syndrome diagnosis have shifted in recent years, this review will discuss rationale and limitations for current strategies as well as provide an overview of future directions in the field.Recent findingsIn recent years, the use of clinical criteria and risk scores for identification of Lynch syndrome has been augmented by universal testing of all newly diagnosed colorectal cancers with molecular methods to screen for mismatch repair deficiency with high sensitivity and speci...
Source: Current Treatment Options in Gastroenterology - Category: Gastroenterology Source Type: research
A 44-year-old man was evaluated for recurrent angioedema manifested as more than 10 discrete episodes with swelling of the posterior pharynx and uvula, without urticaria, that would subside spontaneously over 24 hours. These episodes were first noted 2 years ago, were worsened by alcohol, and were not responsive to antihistamines. Medical history was significant for hyperestrogenism, that worsened with testosterone treatment for infertility. His primary family history revealed a father and brother with gynecomastia, a mother with endometrial cancer, and a sister with Lynch syndrome.
Source: Annals of Allergy, Asthma and Immunology - Category: Allergy & Immunology Authors: Source Type: research
Lynch syndrome (LS) is an autosomal dominant hereditary cancer predisposition syndrome caused by pathogenic germline variants in DNA mismatch repair genes (MMR) MLH1, MSH2, MSH6 and PMS2. LS accounts for 3 –5% of all colorectal cancers (CRC). LS associated CRC generally has microsatellite instability and lacks for MMR protein expression. The risk of CRC in LS patients is between 10 and 82% depending on the involved MMR gene. LS patients are at high risk to develop synchronous/metachronous cancer bot h colonic and extracolonic (e.g.
Source: Digestive and Liver Disease - Category: Gastroenterology Authors: Tags: Correspondence Source Type: research
ConclusionWe found a novel largeEPCAM-MSH2 duplication associated with LS and the presence of LOHs in regions containing numerous tumor suppressors, raising the hypothesis that these alterations could contribute to cancer susceptibility. Our results underline the importance to deepen the knowledge of molecular mechanisms in order to determine the role in cancer predisposition of novel genetic alterations.
Source: International Journal of Colorectal Disease - Category: Gastroenterology Source Type: research
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