title: Early-onset colorectal cancer: a sporadic or inherited disease?
abstract: Colorectal cancer is the third most common cancer diagnosed worldwide. Although epidemiology data show a marked variability around the world, its overall incidence rate shows a slow but steady decrease, mainly in developed countries. Conversely, early-onset colorectal cancer appears to display an opposite trend with an overall prevalence in United States and European Union ranging from 3.0% and 8.6%. Colorectal cancer has a substantial proportion of familial cases. In particular, early age at onset is especially suggestive of hereditary predisposition. The clinicopathological and molecular features of colorectal cancer cases show a marked heterogeneity not only between early- and late-onset cases but also within the early-onset group. Two distinct subtypes of early-onset colorectal cancers can be identified: a "sporadic" subtype, usually without family history, and an inherited subtype arising in the context of well defined hereditary syndromes. The pathogenesis of the early-onset disease is substantially well characterized in the inherited subtype, which is mainly associated to the Lynch syndrome and occasionally to other rare mendelian diseases, whereas in the "sporadic" subtype the origin of the disease may be attributed to the presence of various common/rare genetic variants, so far largely unidentified, displaying variable penetrance. These variants are thought to act cumulatively to increase the risk of colorectal cancer, and presumably to also anticipate its onset. Efforts are ongoing in the attempt to unravel the intricate genetic basis of this "sporadic" early-onset disease. A better knowledge of molecular entities and pathways may impact on family-tailored prevention and clinical management strategies.
authors.affiliation: Vittoria Stigliano, Lupe Sanchez-Mete, Marcello Anti, Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Stigliano
authors.affiliation: Vittoria Stigliano, Lupe Sanchez-Mete, Marcello Anti, Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Lupe
authors.initials: L
authors.lastname: Sanchez-Mete
authors.affiliation: Vittoria Stigliano, Lupe Sanchez-Mete, Marcello Anti, Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Aline
authors.initials: A
authors.lastname: Martayan
authors.affiliation: Vittoria Stigliano, Lupe Sanchez-Mete, Marcello Anti, Division of Gastroenterology and Digestive Endoscopy, Regina Elena National Cancer Institute, 00144 Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Anti
mesh_terms: D000328:Adult; D017668:Age of Onset; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D040941:Heredity; D006801:Humans; D008297:Male; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010580:Peutz-Jeghers Syndrome / Q000453:epidemiology / Q000235:genetics; D010641:Phenotype; D015995:Prevalence; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
keywords: Early-onset colorectal cancer; Epidemiology; Hereditary syndrome; Lynch syndrome; MUTYH-associated polyposis