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Molecular Features and Methylation Status in Early Onset (≤40 Years) Colorectal Cancer: A Population Based, Case-Control Study

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      Abstract

      Colorectal cancer is usually considered a disease of the elderly. However, a small fraction of patients develops colorectal cancer earlier. The aim of our study was to define the frequency of known hereditary colorectal syndromes and to characterise genetic and epigenetic features of early nonhereditary tumors. Thirty-three patients ≤40 years with diagnosis of colorectal cancer and 41 patients with disease at >60 years of age were investigated for MSI, Mismatch Repair proteins expression, KRAS and BRAF mutations, hypermethylation, and LINE-1 hypomethylation. Detection of germline mutations was performed in Mismatch Repair, APC and MUTYH genes. Early onset colorectal cancer showed a high incidence of hereditary forms (18%). KRAS mutations were detected in 36% of early nonhereditary tumors. Early onset colorectal cancer disclosed an average number of methylated genes significantly lower when compared to the controls ( p = 0.02). Finally both of the two groups were highly methylated in ESR1, GATA5, and WT1 genes and were similar for LINE-1 hypomethylation. The genetic make-up of carcinomas differs from young to elderly patients. Early onset tumors showed more frequently a constitutional defective of Mismatch Repair System and a minor number of methylated genes. Hypermethylation of ESR1, GATA5, and WT1 genes suggests possible markers in the earlier diagnosis of colorectal tumorigenesis.

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        The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM.

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            Author and article information

            Affiliations
            1Dipartimento di Medicina Diagnostica, Clinica e Sanità Pubblica, Università di Modena e Reggio Emilia, 41124 Modena, Italy
            2Dipartimento di Chirurgia e Scienze Morfologiche, Università dell'Insubria, 21100 Varese, Italy
            3Divisione di Anatomia Patologica, Policlinico di Modena, 41124 Modena, Italy
            Author notes

            Academic Editor: Miroslav Zavoral

            Journal
            Gastroenterol Res Pract
            Gastroenterol Res Pract
            GRP
            Gastroenterology Research and Practice
            Hindawi Publishing Corporation
            1687-6121
            1687-630X
            2015
            19 October 2015
            : 2015
            4629034 10.1155/2015/132190
            Copyright © 2015 Giulia Magnani et al.

            This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Categories
            Research Article

            Gastroenterology & Hepatology

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