Search results for "perinnölliset taudit"
showing 10 items of 18 documents
Lack of association between screening interval and cancer stage in Lynch syndrome may be accounted for by over-diagnosis; a prospective Lynch syndrom…
2019
Background Recent epidemiological evidence shows that colorectal cancer (CRC) continues to occur in carriers of pathogenic mismatch repair (path_MMR) variants despite frequent colonoscopy surveillance in expert centres. This observation conflicts with the paradigm that removal of all visible polyps should prevent the vast majority of CRC in path_MMR carriers, provided the screening interval is sufficiently short and colonoscopic practice is optimal. Methods To inform the debate, we examined, in the Prospective Lynch Syndrome Database (PLSD), whether the time since last colonoscopy was associated with the pathological stage at which CRC was diagnosed during prospective surveillance. Path_MMR…
A rare disease and education : Neurofibromatosis type 1 decreases educational attainment
2021
Rare heritable syndromes may affect educational attainment. Here, we study education in neurofibromatosis 1 (NF1) that is associated with multifaceted medical, social and cognitive consequences. Educational attainment in the Finnish population‐based cohort of 1408 individuals with verified NF1 was compared with matched controls using Cox proportional hazards model with delayed entry and competing risk for death. Moreover, models accounting for the effects of cancer at age 15–30 years, parental NF1 and developmental disorders were constructed. Overall, the attainment of secondary education was reduced in individuals with NF1 compared to controls (hazard ratio 0.83, 95%CI 0.74–0.92). History …
Does breast carcinoma belong to the Lynch syndrome tumor spectrum? : Somatic mutational profiles vs. ovarian and colorectal carcinomas
2020
// Noora K. Porkka 1 , Alisa Olkinuora 1 , Teijo Kuopio 2 , 3 , Maarit Ahtiainen 4 , Samuli Eldfors 5 , Henrikki Almusa 5 , Jukka-Pekka Mecklin 6 , 7 , 8 and Paivi Peltomaki 1 1 Department of Medical and Clinical Genetics, University of Helsinki, Helsinki, Finland 2 Department of Pathology, Jyvaskyla Central Hospital, Jyvaskyla, Finland 3 Department of Biological and Environmental Science, University of Jyvaskyla, Jyvaskyla, Finland 4 Department of Education and Research, Jyvaskyla Central Hospital and University of Eastern Finland, Jyvaskyla, Finland 5 Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland 6 Faculty of Sport and Health Sciences, University of J…
Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Sy…
2021
Abstract Purpose To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR ( path_MMR ) variants. Methods The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. Results Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1 , path_MSH2 , path_MSH6 , and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and…
WNT2 activation through proximal germline deletion predisposes to small intestinal neuroendocrine tumors and intestinal adenocarcinomas
2021
Abstract Many hereditary cancer syndromes are associated with an increased risk of small and large intestinal adenocarcinomas. However, conditions bearing a high risk to both adenocarcinomas and neuroendocrine tumors are yet to be described. We studied a family with 16 individuals in four generations affected by a wide spectrum of intestinal tumors, including hyperplastic polyps, adenomas, small intestinal neuroendocrine tumors, and colorectal and small intestinal adenocarcinomas. To assess the genetic susceptibility and understand the novel phenotype, we utilized multiple molecular methods, including whole genome sequencing, RNA sequencing, single cell sequencing, RNA in situ hybridization…
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…
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…
Predicting intention to participate in self-management behaviors in patients with Familial Hypercholesterolemia: A cross-national study.
2019
Rationale. Familial Hypercholesterolemia (FH) is a genetic condition that predisposes patients to substantially increased risk of early-onset atherosclerotic cardiovascular disease. FH risks can be minimized through regular participation in three self-management. Behaviors. physical activity, healthy eating, and taking cholesterol lowering medication. Objective. The present study tested the effectiveness of an integrated social cognition model in predicting intention to participate in the self-management behaviors in FH patients from seven countries. Method. Consecutive patients in FH clinics from Australia, Hong Kong, Brazil, Malaysia, Taiwan, China, and UK (total N = 726) completed measur…
Schizophrenia polygenic risk score and long-term success in the labour market: A cohort study
2022
Publisher Copyright: © 2022 The Authors Employment is rare among people with a schizophrenia diagnosis. Meanwhile, a genetic liability for schizophrenia may hinder labour market performance. We studied how the polygenic risk score (PGS) for schizophrenia related to education and labour market outcomes. We found that a higher PGS was linked to lower educational levels and weaker labour market outcomes as well as a higher likelihood of receiving social income transfers, particularly among men. Assuming that the link is causal, our results indicate that individuals with schizophrenia or schizophrenia-related traits have a weakened ability to fully participate in the labour market, potentially …
No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Data…
2021
Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic …