A high degree of LINE-1 hypomethylation is a unique feature of early-onset colorectal cancer

• Published in: PloS one 2012-09, Vol.7 (9), p.e45357-e45357
• Main Authors: Antelo, Marina, Balaguer, Francesc, Shia, Jinru, Shen, Yan, Hur, Keun, Moreira, Leticia, Cuatrecasas, Miriam, Bujanda, Luis, Giraldez, Maria Dolores, Takahashi, Masanobu, Cabanne, Ana, Barugel, Mario Edmundo, Arnold, Mildred, Roca, Enrique Luis, Andreu, Montserrat, Castellvi-Bel, Sergi, Llor, Xavier, Jover, Rodrigo, Castells, Antoni, Boland, C Richard, Goel, Ajay
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adenoma - epidemiology; Adenoma - genetics; Adenoma - metabolism; Adenoma - mortality; Adult; Age; Age of Onset; Analysis; Argentina - epidemiology; Bioindicators; Biomarkers; Cancer; Case-Control Studies; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - mortality; Colorectal Neoplasms, Hereditary Nonpolyposis - epidemiology; Colorectal Neoplasms, Hereditary Nonpolyposis - genetics; Colorectal Neoplasms, Hereditary Nonpolyposis - metabolism; Colorectal Neoplasms, Hereditary Nonpolyposis - mortality; Càncer; Càncer colorectal; Deoxyribonucleic acid; DNA; DNA Glycosylases - genetics; DNA Methylation; DNA-Binding Proteins - genetics; Epidemiologia genètica; Epigenetics; Female; Gastroenterology; Gene Expression; Genetic aspects; Genetic disorders; Genetic epidemiology; Germ-Line Mutation; Health aspects; Humans; Internal medicine; Long Interspersed Nucleotide Elements; Male; Medical diagnosis; Medicine; Methylation; Microsatellite Instability; Middle Aged; Mismatch repair; MLH1 protein; Mucosa; Mutation; MutL Protein Homolog 1; MutS Homolog 3 Protein; Nuclear Proteins - genetics; Oncology; Pathology; Physiological aspects; Prognosis; Proto-Oncogene Proteins B-raf - genetics; Spain - epidemiology; Stability; Survival Analysis; Tissues; Tumors; United States - epidemiology; Young adults
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0045357

Early-onset colorectal cancer (CRC) represents a clinically distinct form of CRC that is often associated with a poor prognosis. Methylation levels of genomic repeats such as LINE-1 elements have been recognized as independent factors for increased cancer-related mortality. The methylation status of LINE-1 elements in early-onset CRC has not been analyzed previously. We analyzed 343 CRC tissues and 32 normal colonic mucosa samples, including 2 independent cohorts of CRC diagnosed ≤ 50 years old (n=188), a group of sporadic CRC >50 years (MSS n=89; MSI n=46), and a group of Lynch syndrome CRCs (n=20). Tumor mismatch repair protein expression, microsatellite instability status, LINE-1 and MLH1 methylation, somatic BRAF V600E mutation, and germline MUTYH mutations were evaluated. Mean LINE-1 methylation levels (± SD) in the five study groups were early-onset CRC, 56.6% (8.6); sporadic MSI, 67.1% (5.5); sporadic MSS, 65.1% (6.3); Lynch syndrome, 66.3% (4.5) and normal mucosa, 76.5% (1.5). Early-onset CRC had significantly lower LINE-1 methylation than any other group (p