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World J Gastroenterol. 2014 Feb 28;20(8):1961-71. doi: 10.3748/wjg.v20.i8.1961.

New genes emerging for colorectal cancer predisposition.

Author information

1
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.

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.

KEYWORDS:

Colorectal neoplasm, genetic predisposition to disease; Genetic variant; Genotype-phenotype correlation; Next generation sequencing; Single nucleotide polymorphism

PMID:
24587672
PMCID:
PMC3934466
DOI:
10.3748/wjg.v20.i8.1961
[Indexed for MEDLINE]
Free PMC Article

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