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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This study aims at examining the frequency, patterns and molecular etiologies of such inter-tumoral MMR discordances. We analyzed a cohort of 2159 colorectal cancer (CRC) patients collected over a 5-year period and found that 1.3% of the patients (27/2159) had  ≥ 2 primary CRCs, and 25.9% of the patients with ≥ 2 primary CRCs (7/27) exhibited inter-tumoral MMR discordance. We then combined the seven MMR-discordant CRC patients with three additional MMR-discordant GIT carcinoma patients and evaluated their discordant patterns and associated mol ecular abnormalities. The 10 patients consiste...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
AbstractThere has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as aBRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39  years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, L...
Source: International Cancer Conference Journal - Category: Cancer & Oncology Source Type: research
ConclusionsOur data is consistent with the results from other studies including US Hispanics, where approximately 10% of Hispanic individuals with colorectal cancer have microsatellite instability. Our results support universal tumor-based screening for LS among Hispanics in accordance with National Comprehensive Cancer Network guidelines.
Source: Journal of Racial and Ethnic Health Disparities - Category: International Medicine & Public Health Source Type: research
bel Trias José Ignacio Busteros Gemma Mateu Francesc Balaguer María-Teresa Fernández-Figueras Manel Esteller Eva Musulén The use of epithelial cell adhesion molecule (EPCAM) immunohistochemistry (IHC) is not included in the colorectal cancer (CRC) screening algorithm to detect Lynch syndrome (LS) patients. The aim of the present study was to demonstrate that EPCAM IHC is a useful tool to guide the LS germ-line analysis when a loss of MSH2 expression was present. We retrospectively studied MSH2 and EPCAM IHC in a large series of 190 lesions composed of malignant neoplasms (102), p...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSION: The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented. PMID: 32956497 [PubMed - as supplied by publisher]
Source: The British Journal of Surgery - Category: Surgery Authors: Tags: Br J Surg Source Type: research
ConclusionsUpdated risk assessment and genetic counseling with a discussion of the benefits and limitations of germline and somatic genetic testing, is essential as the understanding of UMMRD and genetic testing recommendations for this population evolve.
Source: Hereditary Cancer in Clinical Practice - Category: Cancer & Oncology Source Type: research
AbstractMicrosatellite instability (MSI) is an effective biomarker for diagnosing Lynch syndrome (LS) and predicting the responsiveness of cancer therapy. MSI testing is conventionally performed by capillary electrophoresis, and MSI status is judged by visual assessment of allele size change. Here, we attempted to develop a quantitative evaluation model of MSI using next-generation sequencing (NGS). Microsatellite markers were analyzed in tumor and non-tumor tissues of colorectal cancer patients by NGS after a single multiplex polymerase chain reaction amplification. The read counts corresponding to microsatellite loci len...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Total abdominal colectomy with prophylactic hysterectomy at 30 years of age was the most cost-effective surgical choice in women with Lynch syndrome and colon cancer. The addition of bilateral salpingo-oophorectomy offered the highest event-free survival and lowest mortality. However, the additional morbidity of premature menopause of prophylactic salpingo-oophorectomy for younger women outweighed the benefit of ovarian cancer prevention. See Video Abstract at http://links.lww.com/DCR/B287. LA CIRUGÍA GINECOLÓGICA PROFILÁCTICA EN EL MOMENTO DE LA COLECTOMÍA BENEFICIA A LAS MUJERE...
Source: Diseases of the Colon and Rectum - Category: Gastroenterology Tags: Original Contributions: Colorectal Cancer Source Type: research
by Neil A. J. Ryan, Raymond McMahon, Simon Tobi, Tristan Snowsill, Shona Esquibel, Andrew J. Wallace, Sancha Bunstone, Naomi Bowers, Ioana E. Mosneag, Sarah J. Kitson, Helena O ’Flynn, Neal C. Ramchander, Vanitha N. Sivalingam, Ian M. Frayling, James Bolton, Rhona J. McVey, D. Gareth Evans, Emma J. Crosbie BackgroundLynch syndrome (LS) predisposes to endometrial cancer (EC), colorectal cancer, and other cancers through inherited pathogenic variants affecting mismatch-repair (MMR) genes. Diagnosing LS in women with EC can reduce subsequent cancer mortality through colonoscopic surveillance and aspirin chemoprevention;...
Source: PLoS Medicine - Category: Internal Medicine Authors: Source Type: research
Publication date: December 2020Source: Cancer Epidemiology, Volume 69Author(s): Anouk H. Eijkelboom, Jesca G.M. Brouwer, Hans F.A. Vasen, Tanya M. Bisseling, Jan J. Koornstra, Ellen Kampman, Fränzel J.B. van Duijnhoven
Source: Cancer Epidemiology - Category: Cancer & Oncology Source Type: research
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