SNP association study in PMS2-associated Lynch syndrome

AbstractLynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly onMLH1, MSH2 andMSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs inPMS2 mutation carriers. A cohort study was performed in 507PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. Discrimination was assessed with a concordance statistic in a bootstrap cross-validation procedure. Individual SNPs only had non-significant associations with CRC occurrence with HRs lower than 2, although male carriers of allele A at rs1321311 (6p21.31) may have increased risk of CRC (HR  = 2.1, 95% CI 1.2–3.0). A polygenic risk score (PRS) based on 24 HRs had an HR of 2.6 (95% CI 1.5–4.6) for the highest compared to the lowest quartile, but had no discriminative ability (c statistic 0.52). Previously suggested SNPs do not modify CRC risk inPMS2 carriers. Future large studies are needed for improved risk stratification among Lynch syndrome patients.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research

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CONCLUSIONS: Universal tumour testing strategies for guiding germline genetic testing of people with incident CRC for LS in Australia are likely to be cost-effective compared with no testing. Universal germline gene panel testing would not currently be cost-effective. PMID: 31595523 [PubMed - as supplied by publisher]
Source: Medical Journal of Australia - Category: General Medicine Tags: Med J Aust Source Type: research
Endoscopy DOI: 10.1055/a-1016-4977ESGE recommends that individuals with Lynch syndrome should be followed in dedicated units that practice monitoring of compliance and endoscopic performance measures.Strong recommendation, low quality evidence, level of agreement 100 %.ESGE recommends starting colonoscopy surveillance at the age of 25 years for MLH1 and MSH2 mutation carriers and at the age of 35 years for MSH6 and PMS2 mutation carriers.Strong recommendation, moderate quality evidence, level of agreement 100 %. ESGE recommends the routine use of high-definition endoscopy systems in individuals with Lynch syndrome. Str...
Source: Endoscopy - Category: Gastroenterology Authors: Tags: Guideline Source Type: research
ConclusionsResults of the Idylla ™ MSI Assay were highly concordant with results of routine tests and lower failure rates were observed. Further advantages are the lack of need for matched normal tissue, the low dependence on pre-analytical conditions, the simplified workflow, the short turnaround times, the automated result inte rpretation, and the very limited hands-on work.Editorial acknowledgementTeams involved in the MSI, Idylla MSI Assay, Colon Rectal Cancer, Multicenter Study.Legal entity responsible for the studyIrblleida.FundingBiocartis.DisclosureX. Matias-guiu: Non-remunerated activity/ies: Biocartis.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
British Journal of Cancer, Published online: 25 September 2019; doi:10.1038/s41416-019-0580-9Type 2 diabetes mellitus, blood cholesterol, triglyceride and colorectal cancer risk in Lynch syndrome
Source: British Journal of Cancer - Category: Cancer & Oncology Authors: Source Type: research
Abstract About 5% of colorectal cancer (CRC) cases occurred in the context of an underlying hereditary predisposition syndrome. Lynch syndrome is the main causes of hereditary CRC but is also associated with a higher risk of other cancers (such as endometrial cancer and ovarian cancer). It is the consequence of constitutional mutation in a MisMatch Repair (MMR) gene, involved in DNA repair: MLH1, MSH2, MSH6 or PMS2; or of the EPCAM gene (MSH2 promotor). If a mutation predisposing to Lynch Syndrome is identified in an individual, special monitoring should be initiated, adapted to estimated cancer risk. Clinical cri...
Source: Presse Medicale - Category: General Medicine Authors: Tags: Presse Med Source Type: research
ConclusionFurther studies should be conducted to provide new insights about survival of colorectal carcinoma in Lynch syndrome, as well as the therapeutic alternatives for this neoplasia.ResumoIntroduçãoO carcinoma colorretal é a terceira neoplasia mais prevalente no mundo, bem como a segunda causa de morte por câncer. A maioria destas neoplasias são esporádicas, devidas a mutações somáticas, mas cerca de 15% são hereditárias como a síndrome de Lynch ou Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Apesar de ser a mesma neoplasia, esta ...
Source: Journal of Coloproctology - Category: Gastroenterology Source Type: research
Dye-based pancolonic chromoendoscopy is recommended for colorectal cancer surveillance in patients with Lynch syndrome. However, there is scarce evidence to support its superiority to high-definition white-light endoscopy. We performed a prospective study assess whether in the hands of high detecting colonoscopists, high-definition, white-light endoscopy is non-inferior to pancolonic chromoendoscopy for detection of adenomas in patients with Lynch syndrome.
Source: Gastroenterology - Category: Gastroenterology Authors: Source Type: research
Authors: Gupta S, Provenzale D, Llor X, Halverson AL, Grady W, Chung DC, Haraldsdottir S, Markowitz AJ, Slavin TP, Hampel H, CGC, Ness RM, Weiss JM, Ahnen DJ, Chen LM, Cooper G, Early DS, Giardiello FM, Hall MJ, Hamilton SR, Kanth P, Klapman JB, Lazenby AJ, Lynch PM, Mayer RJ, Mikkelson J, CGC, Peter S, Regenbogen SE, Dwyer MA, CGC, Ogba N Abstract Identifying individuals with hereditary syndromes allows for improved cancer surveillance, risk reduction, and optimized management. Establishing criteria for assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCC...
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
This study aimed to investigate the spectrum of germ-line mutations in Russian LS patients. LS-related mismatch repair (MMR) genes were analyzed in 16 patients, who were forwarded to genetic testing due to strong clinical features of LS and had high-level microsatellite instability (MSI-H) in the tumor (n = 14) or unknown MSI status (n = 2). In addition, 672 consecutive colorectal cancer (CRC) cases were screened for family history; 15 patients were younger than 50 years and reported 2 or more instances of LS-related cancers in 1st- or 2nd-degree relatives. Seven of these cases demonstrated MSI-H and th...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
Lynch syndrome is a genetic condition that increases a person ’s risk of developing colorectal cancer. Learn more about its symptoms, diagnosis, and treatment here.
Source: Health News from Medical News Today - Category: Consumer Health News Tags: Colorectal Cancer Source Type: news
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