Survival by colon cancer stage and screening interval in Lynch syndrome: a prospective Lynch syndrome database report

AbstractBackgroundWe previously reported that in pathogenic mismatch repair (path_MMR) variant carriers, the incidence of colorectal cancer (CRC) was not reduced when colonoscopy was undertaken more frequently than once every 3 years, and that CRC stage and interval since last colonoscopy were not correlated.MethodsThe Prospective Lynch Syndrome Database (PLSD) that records outcomes of surveillance was examined to determine survival after colon cancer in relation to the time since previous colonoscopy and pathological stage. Onlypath_MMR variants scored by the InSiGHT variant database as class 4 or 5 (clinically actionable) were included in the analysis.ResultsNinety-ninepath_MMR carriers had no cancer prior to or at first colonoscopy, but subsequently developed colon cancer. Among these, 96 were 65  years of age or younger at diagnosis, and included 77path_MLH1, 17path_MSH2, and 2path_MSH6 carriers. The number of cancers detected within  3.5 years after previous colonoscopy were 9, 43, 31 and 13, respectively. Of these, 2, 8, 4 and 3 were stage III, respectively, and only one stage IV (interval 2.5–3.5 years) disease. Ten-year crude survival after colon cancer were 93, 94 and 82% for stage I, II and III disease, respectivel y (p 
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research

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Abstract The gut microbiota has been associated with colorectal cancer (CRC), but causal alterations preceding CRC have not been elucidated. To prospectively assess microbiome changes prior to colorectal neoplasia, we investigated samples from 100 Lynch syndrome patients using 16S rRNA gene sequencing of colon biopsies, coupled with metagenomic and metatranscriptomic sequencing of feces. Colectomy and CRC history represented the largest effects on microbiome profiles. A subset of Clostridiaceae were depleted in stool corresponding with baseline adenomas, while Desulfovibrio was enriched both in stool and in mucosa...
Source: Cell Host and Microbe - Category: Microbiology Authors: Tags: Cell Host Microbe Source Type: research
DR ROBERT CIMA (Rochester, MN): The authors present a single-institution experience of patients with genetically confirmed Lynch syndrome, who underwent segmental colectomy as treatment for index colon cancer. The natural history of these patients is not well described in the literature, and it suggests it is tied to their underlying genetic profile.
Source: Journal of the American College of Surgeons - Category: Surgery Tags: Southern surgical association article Source Type: research
PB, Shia J, Schultz N, Garcia-Aguilar J, Diaz LA, Goodman K, Saltz LB, Weiser MR, Smith JJ, Stadler ZK Abstract PURPOSE: Evaluate response of mismatch repair deficient (dMMR) rectal cancer to neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: dMMR rectal tumors at Memorial Sloan Kettering were retrospectively reviewed for characteristics, treatment, and outcomes. Fifty dMMR rectal cancer patients were identified by immunohistochemistry and/or microsatellite instability analysis, with initial treatment response compared to a matched pMMR rectal cancer cohort. Germline and somatic mutation analyses were evaluated....
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
AbstractIndividuals who carry pathogenic mutations in DNA mismatch repair (MMR) genes have high risks of cancer, and small studies have suggested that these risks depend on the sex of the parent from whom the mutation was inherited. We have conducted the first large study of such a parent-of-origin effect (POE). Our study was based on all MMR gene mutation carriers and their relatives in the Colon Cancer Family Registry, comprising 18,226 people. The POE was estimated as a hazard ratio (HR) using a segregation analysis approach that adjusted for ascertainment. HR  = 1 corresponds to no POE and HR > ...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
ConclusionThe patient presented represents the first reported case where both next generation sequencing (NGS) forBRCA LOH and MMR IHC testing of her breast cancer were performed and underscores the importance of using NGS including the reported mutational allelic frequency (MAF) and IHC use to predict the likely responsiveness to the recently approved PARP inhibitors and checkpoint inhibitor therapies (Robson et al in N Engl J Med 377:523 –533, 2017, Lemery et al in 377(15):1409–1412,https://doi.org/10.1056/NEJMp1709968, 2017), key because the gatekeeper transforming event for tumors related to inherited cance...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
Conclusions Lynch syndrome should be suspected in families with familial pancreatic cancer, even in the absence of colon cancers. Specifically, our observation supports the association between the MSH6 c.2194C>T pathogenic variant and extracolonic tumours and it suggests that MSH6 pathogenic variants are associated with familial pancreatic cancer more frequently than assumed.
Source: European Journal of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Original Articles: Gastroenterology Source Type: research
ConclusionIdentification of families with Lynch syndrome, while challenging because of variable phenotypes at diagnosis, is feasible with available molecular biological technologies and crucial to reduce mortality caused by this syndrome.
Source: Journal of Gastrointestinal Cancer - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: A simplified pedigree is acceptable for selecting candidates to screen for hereditary colorectal cancer, whereas an extended pedigree is still required for a more precise diagnosis of Lynch syndrome, especially in younger patients. See Video Abstract at http://links.lww.com/DCR/B97. EXTENSIÓN DE PEDIGREE REQUERIDO EN LA DETECCIÓN Y DIAGNÓSTICO DE CÁNCER COLORRECTAL HEREDITARIO SIN POLIPOSIS: COMPARACIÓN DE LOS PEDIGREES SIMPLIFICADO Y EL EXTENDIDO ANTECEDENTES: La obtención de un Pedigree exacto es el primer paso para reconocer un paciente con cáncer color...
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research
Authors: Lappalainen J, Holmström D, Lepistö A, Saarnio J, Mecklin JP, Seppälä T Abstract Background: 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 surveillance. Lynch syndrome (LS) registries have been criticized for not reporting colonoscopy quality adequately.Methods: Prospective follow-up data from the national registry were combined with a retrospective assessment of the colonoscopy reports from Helsinki University Hospital electronic patients records in 2004-201...
Source: Scandinavian Journal of Gastroenterology - Category: Gastroenterology Tags: Scand J Gastroenterol Source Type: research
Rationale: Lynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation-induced LS-associated endometrial cancer (LSAEC) was rarely reported. Patient concerns: A 26-year-old female patient suffered from prolonged menstrual period and increased menstrual flow for 2 months. Diagnoses: The patient was diagnosed with cervix CIN III, endometrial cancer (EC), anemia, and LS. Interventions: Total hysterectomy, bilateral salpingectomy, pelvic lymphadenectomy were performed for treatin...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
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