New genes emerging for colorectal cancer predisposition.
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.
['Esteban-Jurado|Clara|C|', 'Garre|Pilar|P|', 'Vila|Maria|M|', 'Lozano|Juan José|JJ|', 'Pristoupilova|Anna|A|', 'Beltrán|Sergi|S|', 'Abulí|Anna|A|', 'Muñoz|Jenifer|J|', 'Balaguer|Francesc|F|', 'Ocaña|Teresa|T|', 'Castells|Antoni|A|', 'Piqué|Josep M|JM|', 'Carracedo|Angel|A|', 'Ruiz-Ponte|Clara|C|', 'Bessa|Xavier|X|', 'Andreu|Montserrat|M|', 'Bujanda|Luis|L|', 'Caldés|Trinidad|T|', 'Castellví-Bel|Sergi|S|']
D011125:Adenomatous Polyposis Coli D015179:Colorectal Neoplasms D003123:Colorectal Neoplasms, Hereditary Nonpolyposis 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
Colorectal neoplasm, genetic predisposition to disease Genetic variant Genotype-phenotype correlation Next generation sequencing Single nucleotide polymorphism