Original article—alimentary tractPrevalence of Alterations in DNA Mismatch Repair Genes in Patients With Young-Onset Colorectal Cancer
Section snippets
Subject Population
Subjects were recruited through the Colon CFR, an international collaboration of 6 participating centers (University of Hawaii, Honolulu, HI; Fred Hutchinson Cancer Research Center, Seattle, WA; Mayo Clinic, Rochester, MN; University of Southern California Consortium, Los Angeles, CA; Cancer Care Ontario, Toronto, Canada; and University of Melbourne, Melbourne, Australia) organized in 1997 to create a comprehensive resource for genetic epidemiology studies. As described elsewhere,18 recruitment
Results
One hundred ninety-five subjects were included in the final analysis cohort, with 91 (47%) men and 104 (53%) women. The mean (standard deviation) age at CRC diagnosis was 42.9 (±6.1) years. Subject characteristics were similarly distributed across the 3 participating Colon CFR sites, with the exception of age at CRC diagnosis (Table 1).
Germline MLH1, MSH2, and MSH6 sequencing data were obtained for 195 (100%), 195 (100%), and 189 (97%) subjects, respectively. Specific MMR gene sequence
Discussion
In this multicenter study of young-onset CRC cases, direct germline analyses of MLH1, MSH2, and MSH6 yielded a prevalence of 5.6% for deleterious/suspected deleterious mutations. This study represents the description of non-triaged MMR gene testing in a North American, population-based sample of young-onset CRC cases. Encouragingly, our findings are consistent with results from a prior, population-based study in Scotland that reported an MMR gene mutation prevalence of 4.4% for CRC cases
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2021, Cancer Treatment and Research CommunicationsCitation Excerpt :Current laboratory assays for MMR testing include either a multiplex polymerase chain reaction (PCR) assay [17], the “Bethesda Panel”, or a multiplex immunohistochemistry (IHC) assay, in order to demonstrate the absence of one of four mismatch repair (MMR) enzymes (MLH1, MSH2, MSH6, and PMS2) [18]. Both assays require cost, additional tumour tissue and produce variable results, with different sensitivity and specificity reported in reference studies [19–22]. Newer approaches are being validated to address these issues, such as deep learning based identification using haematoxylin and eosin-stained slides [23].
Young-onset colorectal cancer: Diagnosis and management
2018, Seminars in Colon and Rectal SurgeryCitation Excerpt :Major hereditary predisposition syndromes only account for up to 16%, or one in six cases, of young-onset CRCs.20,21 This proportion varies by the institutional practices of those reporting the case series, the age range included in the study, and the exact methods for ascertaining the diagnosis of hereditary syndromes.21–25 Earlier studies mainly utilized family history and tumor MSI testing, while more recent studies have additionally included the next-generation sequencing multiplex cancer susceptibility gene panel testing.
Germline Genetic Features of Young Individuals With Colorectal Cancer
2018, GastroenterologyCitation Excerpt :Historically, it had been estimated that hereditary cancer syndromes were implicated in up to 5% of all CRC cases.5,12 Based on previous published studies that noted that most young patients with CRC had no family history of cancer, with germline mutations identified in only 5% to 10%,23,25 it had been assumed that the vast majority of cases were not “genetic.” However, it is important to note that these studies relied on family history and tumor phenotypes to select individuals for germline testing, with sequencing focusing largely on genes associated with Lynch syndrome and FAP.
Conflicts of interest The authors disclose the following: Dr Limburg served as a consultant for Genomic Health, Inc, from August 12, 2008, to April 19, 2010. The remaining authors disclose no conflicts.
Funding Funding for and conduct of the gene mutation analyses were provided by Myriad Genetic Laboratories, Salt Lake City, UT. The Colon Cancer Family Registry is supported by NIH National Cancer Institute grants CA074783 (Ontario Registry for Studies of Familial Colorectal Cancer), U01 CA074800 (Mayo Clinic Cooperative Family Registry for Colon Cancer Studies), and U01 CA074799 (USC Familial Colorectal Neoplasia Collaborative Group), as well as U01 CA097735 (Australian Colorectal Cancer Family Registry), UO1 CA074794 (Seattle Colorectal Cancer Family Registry), and U01 CA074806 (University of Hawaii Colorectal Cancer Family Registry).
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