HNPCC

Purpose: To describe a case of retinal arterial macroaneurysm (RAM) in a patient with hereditary nonpolyposis colon cancer (HNPCC)/Lynch syndrome. Methods: A case and its findings were analyzed. Results : A 68-year-old woman presented with a recent history of decreased near vision in the left eye. Both eyes had a visual acuity of 20/20 with normal intraocular pressure. The right retina was normal. The left retina had a focal dilation of the retinal arteriole with a surrounding hemorrhage and lipid in the inferonasal quadrant...

BACKGROUND: Persons with hereditary cancer syndromes (carriers) have a higher risk of developing cancer early. They are confronted with decisions regarding prophylactic surgeries, communication within their families, and childbearing. The present study aims to assess distress, anxiety, and depression in adult carriers and identify risk groups and predictors; clinicians can use to screen for particularly distressed persons. METHODS: N = 223 participants (n = 200 women, n = 23 men) with different hereditary cancer syndromes affected and unaffected by cancer answered questionnaires measuring their distress, anxiety, and depression levels...

OBJECTIVES: This study aimed to investigate colorectal cancer-related knowledge, health beliefs, and screening behaviour in first-degree relatives (FDRs) of patients with Lynch syndrome-associated colorectal cancer (CRC) and explore the predictive factors of screening behaviour based on a health belief model. METHODS: This cross-sectional study was conducted in the colorectal department of a Class A tertiary hospital in Guangzhou from December 2017 to December 2019...

BACKGROUND AND OBJECTIVES: Modest data exist on the benefits of screening and surveillance for pancreatic cancer (PC) in high-risk individuals. Intraductal papillary mucinous neoplasms (IPMN) are known precursors to PC. We hypothesized that patients with high-risk deleterious germline mutations have a higher prevalence of IPMN. METHODS: All patients undergoing prospective screening at a single institution from 2013 to 2019 were reviewed. RESULTS: Of 1166 patients screened, 358 (31%) possessed germline mutations and/or family history of PC (mutations n = 201/358, 56%, family history n = 226/358, 63%) (median follow-up 2...

BACKGROUND: Visceral malignancies in patients with Lynch syndrome behave less aggressively than in those without Lynch syndrome. The behavior of sebaceous carcinoma (SC) in Muir-Torre syndrome (MTS), a variant of Lynch syndrome, is incompletely investigated. OBJECTIVE: Investigate features and survival of SC patients with and without MTS. METHODS: Retrospective cohort study in the Surveillance, Epidemiology, and End Results 17 database from 2000-2019 of patients with SC...

BACKGROUND/AIM: Lynch syndrome (LS) is the secondary cause of hereditary ovarian cancer (OC). Germline mutations in the DNA-mismatch repair (MMR) genes cause tumorigenesis and a high immunogenicity. Recent studies showed a promising use of immunotherapy in MMR deficient (MMRd) tumors. This is a case report of a patient with LS-associated OC and a complete response to pembrolizumab. CASE REPORT: A 44-year-old patient was admitted to the hospital with lower abdominal pain...

Carriers of any pathogenic variant in one of the MMR genes ( path_MMR carriers) were traditionally thought to be at comparable risk of developing a range of different malignancies, foremost colorectal cancer (CRC) and endometrial cancer. However, it is now widely accepted that their cancer risk and cancer spectrum range notably depending on which MMR gene is affected. Moreover, there is increasing evidence that the MMR gene affected also influences the molecular pathogenesis of Lynch syndrome CRC. Although substantial progress has been made over the past decade in understanding these differences, many questions remain unanswered, especially pertaining to path _ PMS2 carriers...

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is a common genetic predisposition to cancer due to germline mutations in genes affecting DNA mismatch repair. Due to mismatch repair deficiency, developing tumors are characterized by microsatellite instability (MSI-H), high frequency of expressed neoantigens and good clinical response to immune checkpoint inhibitors. Granzyme B (GrB) is the most abundant serine protease in the granules of cytotoxic T-cells and natural killer cells, mediating anti-tumor immunity...

Hereditary colorectal cancer (hCRC) represents a major diagnostic and therapeutic challenge. In addition to the usual diagnostic methods, the family history, histological confirmation and mutation analysis play an important role in identifying the type of hereditary CRC. The diagnosis and classification of hCRC are carried out based on the anamnesis, clinical presentation and histology and the further treatment is determined depending on the underlying type of hCRC. For familial adenomatous polyposis (FAP) coloproctomucosectomy after the end of puberty is always recommended, whereas the treatment recommendations for other forms, such as attenuated FAP (aFAP), MUTYH-associated polyposis (MAP) and hereditary nonpolyposis colon cancer (HNPCC, Lynch syndrome), range from close surveillance and endoscopic control, through segmental resection up to colectomy...

Hereditary cancer syndromes (HCS) are genetic diseases with an increased risk of developing cancer. This research describes the implementation of a cancer prevention model, genetic counseling, and germline variants testing in an oncologic center in Mexico. A total of 315 patients received genetic counseling, genetic testing was offered, and 205 individuals were tested for HCS. In 6 years, 131 (63.90%) probands and 74 (36.09%) relatives were tested. Among the probands, we found that 85 (63.9%) had at least one germline variant...

INTRODUCTION: Patients with Lynch syndrome (LS) have an increased lifetime risk of pancreatic cancer (PC) and biliary tract cancer (BTC). These cancers have a notoriously pessimistic prognosis due to late diagnosis and limited therapeutic options. There are limited data based on small cohorts reviewing PC and BTC in LS patients. METHODS: In this retrospective study of the Lynch Syndrome Registry of Finland (LSRFi), records of genetically verified LS patients diagnosed with PC or BTC between 1982 and 2020 were analyzed...

BACKGROUND: Little is known about patient-specific risk factors for skin neoplasia in individuals with Lynch Syndrome (LS). OBJECTIVE: Identify clinical factors associated with development of skin neoplasms in LS. METHODS: Clinical data were systematically collected on a cohort of LS carriers (confirmed pathogenic germline variants [PGVs] in MLH1, MSH2, MSH6, PMS2, or EPCAM) age ≥18 undergoing clinical genetics care at Dana-Farber Cancer Institute from 1/2000-3/2020...

BACKGROUND: Lynch syndrome is one of the most common cancer predisposition syndromes. It is caused by inherited changes in the mismatch repair pathway. With current diagnostic approaches, a causative genetic variant can be found in less than 50% of cases. A correct diagnosis is important for ensuring that an appropriate surveillance program is used and that additional high-risk family members are identified. METHODS: We used clinical genome sequencing on DNA from blood and subsequent transcriptome sequencing for confirmation...

BACKGROUND: Early-onset colorectal cancer (EOCRC) has been increasing in incidence worldwide but its genomic pathogenesis is mostly undetermined. This study aimed to identify robust EOCRC-specific gene expression patterns in non-familial adenomatous polyposis (FAP) and non-hereditary nonpolyposis colorectal cancer syndrome (HNPCC) EOCRC. METHOD: We first performed gene expression profiling analysis using RNA sequencing of discovery cohort comprised of 49 EOCRC (age <50) and 50 late-onset colorectal cancer (LOCRC) (age >70) specimens...

BACKGROUND: The association between Lynch syndrome (LS) and a higher risk of upper tract urothelial carcinoma is well established, but its effect on the risk of bladder and kidney cancers remains controversial. This review aimed to compare the relative risk (RR) of bladder and kidney cancer in confirmed LS germline mutation carriers compared to the general population. METHODS: Medline, Embase, Cochrane Central, and Google Scholar were searched on 14 July 2022 for studies published in English that reported on the rates of urological cancer in adults with confirmed LS germline mutation...

MMR gene germline mutations are considered a major genetic disorder in patients with hereditary nonpolyposis colon cancer (HNPCC) or Lynch syndrome; A total of 15% of sporadic colon carcinomas are MSI-High. MSI has also been observed in other cancers, such as endometrial, gastric, and ovarian cancer. The aim of the current study was to correlate and outline the optimal method between the molecular testing of the instability of microsatellite DNA regions (MSI status) and the loss of protein expression by immunehistochemistry (MMR)...

PURPOSE: Whereas most human genes encode multiple mRNA isoforms with distinct function, clinical workflows for assessing this heterogeneity are not readily available. This is a substantial shortcoming, considering that up to 25% of disease-causing gene variants are suspected of disrupting mRNA splicing or mRNA abundance. Long-read sequencing can readily portray mRNA isoform diversity, but its sensitivity is relatively low due to insufficient transcriptome penetration. METHODS: We developed and applied capture-based target enrichment from patient RNA samples combined with Oxford Nanopore long-read sequencing for the analysis of 123 hereditary cancer transcripts (capture and ultradeep long-read RNA sequencing (CAPLRseq))...

Cancer is one of the most common causes of death worldwide. A strong predisposition to cancer is generally only observed in colorectal cancer (5% of cases) and breast cancer (2% of cases). Colorectal cancer is the most common cancer with a strong genetic predisposition, but it includes dozens of various syndromes. This group includes familial adenomatous polyposis, attenuated familial adenomatous polyposis, MUTYH -associated polyposis, NTHL1 -associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, Lynch syndrome, and Muir-Torre syndrome...

RISK AND PROTECTIVE FACTORS FOR COLORECTAL CANCER Behaviour and environment play a more important role than heredity in colorectal carcinogenesis. The proportion of colorectal cancers (CRCs) attributable to occupational exposure, pollution or poor socio- economic status is low. The risk levels on which the French CRC screening recommendations are based are obsolete and need to be updated. An individual with one or two non-advanced adenomas resected at colonoscopy is at low risk of CRC. Only a first-degree family history of CRC in one parent before age 50 or in two parents at any age confers a significant increased risk...

MICROSATELLITE INSTABILITY IN ENDOMETRIAL CANCERS The microsatellite instability reflects genetic instability that can be sought in tumors, using two methods, immunohistochemistry and molecular biology. Currently in France, a systematic evaluation of microsatellites is recommended in any endometrial cancer from diagnosis. The interest of this evaluation is threefold: diagnostic, prognostic and therapeutic. The presence of microsatellite instability in endometrial cancer allows to detect Lynch syndrome, a hereditary cancer predisposition syndrome, in some patients...