title: New genes emerging for colorectal cancer predisposition.
abstract: Colorectal cancer (CRC) is one of the most frequent neoplasms and an important cause of mortality in the developed world. This cancer is caused by both genetic and environmental factors although 35% of the variation in CRC susceptibility involves inherited genetic differences. Mendelian syndromes account for about 5% of the total burden of CRC, with Lynch syndrome and familial adenomatous polyposis the most common forms. Excluding hereditary forms, there is an important fraction of CRC cases that present familial aggregation for the disease with an unknown germline genetic cause. CRC can be also considered as a complex disease taking into account the common disease-commom variant hypothesis with a polygenic model of inheritance where the genetic components of common complex diseases correspond mostly to variants of low/moderate effect. So far, 30 common, low-penetrance susceptibility variants have been identified for CRC. Recently, new sequencing technologies including exome- and whole-genome sequencing have permitted to add a new approach to facilitate the identification of new genes responsible for human disease predisposition. By using whole-genome sequencing, germline mutations in the POLE and POLD1 genes have been found to be responsible for a new form of CRC genetic predisposition called polymerase proofreading-associated polyposis.
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Esteban-Jurado
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Garre
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Vila
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lozano
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Pristoupilova
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Beltrán
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Abulí
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Muñoz
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Balaguer
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Ocaña
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Castells
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Piqué
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Carracedo
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Ruiz-Ponte
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Bessa
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Andreu
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Caldés
authors.affiliation: Clara Esteban-Jurado, Anna Abulí, Jenifer Muñoz, Francesc Balaguer, Teresa Ocaña, Antoni Castells, Josep M Piqué, Sergi Castellví-Bel, Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Castellví-Bel
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000175:diagnosis / Q000235:genetics; D004777:Environment; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D005843:Geography; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA
keywords: Colorectal neoplasm, genetic predisposition to disease; Genetic variant; Genotype-phenotype correlation; Next generation sequencing; Single nucleotide polymorphism