title: Age at onset should be a major criterion for subclassification of colorectal cancer.
abstract: An important proportion of early-onset colorectal cancer (CRC) does not show a hereditary component with limited knowledge about its molecular basis and features. We analyzed a subset of patients with early-onset CRC and compared them with patients with late-onset CRC. We analyzed the microsatellite instability and CpG island methylator phenotype (CIMP) in both populations and classified them into four molecular subtypes. We analyzed the differential features between groups. Only 12 of 81 early-onset cases (15%) showed microsatellite instability, 10 of which (83%) were Lynch syndrome cases; microsatellite instability cases in elderly patients were sporadic. Early-onset microsatellite-stable cases showed different tumor locations and more family history of cancer than the elderly. Microsatellite instability/CIMP-high early-onset CRC was associated with Lynch syndrome, whereas the elderly cases were associated with BRAF mutations. Early-onset microsatellite-stable/CIMP-high CRCs were more frequently mucinous and right sided than elderly cases, with a high incidence of Lynch syndrome neoplasms; early-onset microsatellite stable/CIMP-low/0 differed from elderly cases in location, stages, incidence of multiple primary neoplasms, and the familial component. The clinical and familial differences observed between early- and late-onset CRC when considering the different carcinogenetic pathways underline that the age at onset criterion should be considered when classifying CRC.
authors.affiliation: Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain. Electronic address: josepereag@hotmail.com.
authors.forename: José
authors.initials: J
authors.lastname: Perea
authors.affiliation: Molecular Biology Laboratory, 12 de Octubre University Hospital, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Rueda
authors.affiliation: Molecular Biology Laboratory, 12 de Octubre University Hospital, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Canal
authors.affiliation: Department of Pathology, 12 de Octubre University Hospital, Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Rodríguez
authors.affiliation: Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain.
authors.forename: Edurne
authors.initials: E
authors.lastname: Álvaro
authors.affiliation: Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Osorio
authors.affiliation: Department of Surgery, 12 de Octubre University Hospital, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alegre
authors.affiliation: Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre, Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Rivera
authors.affiliation: Molecular Biology Laboratory, 12 de Octubre University Hospital, Madrid, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Martínez
authors.affiliation: Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre, Madrid, Spain; Center for Biomedical Network Research on Rare Diseases, Carlos III Health Institute, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Benítez
authors.affiliation: Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre, Madrid, Spain; Center for Biomedical Network Research on Rare Diseases, Carlos III Health Institute, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Urioste
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D015179:Colorectal Neoplasms / Q000145:classification* / Q000453:epidemiology / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf