Search results for "Lynch"
showing 10 items of 56 documents
Incident colorectal cancer in Lynch syndrome is usually not preceded by compromised quality of colonoscopy
2019
AbstractBackground: Lifetime incidence of colorectal cancer (CRC) especially in carriers of MLH1 and MSH2 pathogenic germline variants in mismatch repair genes is high despite ongoing colonoscopy s...
The “unnatural” history of colorectal cancer in Lynch syndrome : lessons from colonoscopy surveillance
2021
Individuals with Lynch syndrome (LS), one of the most common inherited cancer syndromes, are at increased risk of developing malignancies, in particular colorectal cancer (CRC). Regular colonoscopy with polypectomy is recommended to reduce CRC risk in LS individuals. However, recent independent studies demonstrated that a substantial proportion of LS individuals develop CRC despite regular colonoscopy. The reasons for this surprising observation confirmed by large prospective studies are a matter of debate. In this review, we collect existing evidence from clinical, epidemiological and molecular studies and interpret them with regard to the origins and progression of LS-associated CRC. Alon…
Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial : Planned 10-Year Follow-up
2022
Abstract The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53…
Epidemiological, clinical and molecular characterization of Lynch‐like syndrome: A population‐based study
2019
Colorectal carcinomas that are mismatch repair (MMR)‐deficient in the absence of MLH1 promoter methylation or germline mutations represent Lynch‐like syndrome (LLS). Double somatic events inactivating MMR genes are involved in the etiology of LLS tumors. Our purpose was to define the clinical and broader molecular hallmarks of LLS tumors and the population incidence of LLS, which remain poorly characterized. We investigated 762 consecutive colorectal carcinomas operated in Central Finland in 2000–2010. LLS cases were identified by a stepwise protocol based on MMR protein expression, MLH1 methylation and MMR gene mutation status. LLS tumors were profiled for CpG Island Methylator Phenotype (…
Factors associated with decision-making on prophylactic hysterectomy and attitudes towards gynecological surveillance among women with Lynch syndrome…
2020
AbstractTo prevent endometrial carcinoma in Lynch syndrome (LS), regular gynecological surveillance visits and prophylactic surgery are recommended. Previous data have shown that prophylactic hysterectomy is an effective means of cancer prevention, while the advantages and disadvantages of surveillance are somewhat unclear. We aimed to evaluate female LS carriers’ attitudes towards regular gynecological surveillance and factors influencing their decision-making on prophylactic surgery that have not been well documented. Pain experienced during endometrial biopsies was also evaluated. Postal questionnaires were sent to LS carriers undergoing regular gynecological surveillance. Questionnaires…
Familial breast cancer in Spain: A retrospective study of family history and clinical/pathologic characteristics from the GEICAM “El Álamo III” proje…
2013
e12513 Background: Family history (FH) of breast cancer (BC), ovarian cancer (OC), and individual features (IF), like early age of onset, bilateral BC, coexistence of BC and OC, and triple negative BC (TNBC) younger than 50 years, are suspicion criteria of hereditary BC. Although it is assumed in the literature that 15-30% of BC cases can be familial BC (FBC), only 5-10% of BC are hereditary, explained by a germline mutation in BRCA1 or 2. Moreover, there is no international consensus to define FBC (e.g. number of relatives affected, age of onset), in contrast with, e.g. Lynch syndrome and Amsterdam/Bethesda criteria, in order to offer genetic counseling. In Spain, there are not population…
Impact of Different Selection Approaches for Identifying Lynch Syndrome-Related Colorectal Cancer Patients: Unity Is Strength
2022
Lynch syndrome (LS) is an inherited genetic condition associated with increased predisposition to colorectal cancer (CRC) and other tumors and is caused by germline mutations in Mismatch Repair (MMR) or EPCAM genes. The identification of LS carriers is currently based on germline testing of subjects with MMR-deficient (dMMR) tumors or fulfilling clinical criteria, but the most efficient strategies to select patients who should be offered genetic testing are yet not well defined. In order to assess the most suitable selection mode to identify LS-related CRC patients, we retrospectively collected and analyzed all clinical and molecular information of 854 CRC patients, recruited from 2013 to 2…
Lynch Syndrome Genetics and Clinical Implications
2023
Lynch syndrome (LS) is one of the most prevalent hereditary cancer syndromes in humans and accounts for some 3% of unselected patients with colorectal or endometrial cancer and 10%-15% of those with DNA mismatch repair-deficient tumors. Previous studies have established the genetic basis of LS predisposition, but there have been significant advances recently in the understanding of the molecular pathogenesis of LS tumors, which has important implications in clinical management. At the same time, immunotherapy has revolu-tionized the treatment of advanced cancers with DNA mismatch repair defects. We aim to review the recent prog-ress in the LS field and discuss how the accumulating epidemiol…
Involvement of large rearrangements in MSH6 and PMS2 genes in southern Italian patients with lynch syndrome
2018
Background and aim of the work: The Lynch Syndrome (LS) is associated with germline mutations in one of the MisMatch Repair (MMR) genes. Most of germline mutations are point variants, followed by large rearrangements that account to 15-55% of all pathogenic mutations. Many study reporting the frequency of large rearrangements in the MLH1 and MSH2 genes were performed, while, little is known about the contribution of large rearrangements in other MMR genes, as PMS2 and MSH6. Therefore, in this study we investigated the involvment of large rearrangements in MSH6 and PMS2 genes in a well-characterized series of 20 LS southern Italian patients. Methods: These large rearrangements are not usuall…
Abstract LB-382: Identification of predisposing genes for small bowel adenocarcinoma by exome sequencing
2018
Abstract Small bowel adenocarcinoma (SBA) is a rare but aggressive cancer type with limited treatment options. Known predisposing factors include Crohn's disease, celiac disease, and hereditary syndromes such as familial adenomatous polyposis (FAP), Lynch syndrome, and Peutz-Jeghers syndrome. Here, our aim was to further characterize genetic susceptibility to SBA in a large population-based cohort and simultaneously demonstrate the ability to utilize tumor-only data to cost-effectively but reliably call germline variants. Information on all SBAs diagnosed in Finland between the years 2003-2011 were collected utilizing the Finnish Cancer Registry that maintains a nation-wide database on all …