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World J Gastrointest Oncol. Dec 15, 2019; 11(12): 1101-1114
Published online Dec 15, 2019. doi: 10.4251/wjgo.v11.i12.1101
Current status of the genetic susceptibility in attenuated adenomatous polyposis
Víctor Lorca, Pilar Garre
Víctor Lorca, Laboratorio de Oncología Molecular, Grupo de Investigación Clínica y Traslacional en Oncología, Hospital Clínico San Carlos, Madrid 28040, Spain
Pilar Garre, Laboratorio de Oncología Molecular, Servicio de Oncología, Hospital Clínico San Carlos, Madrid 28040, Spain
Author contributions: Lorca V generated the figures and wrote the manuscript; Garre P designed the aim of the review and wrote the manuscript.
Conflict-of-interest statement: Authors declare no potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Pilar Garre, PhD, Research Scientist, Laboratorio de Oncología Molecular, Servicio de Oncología, Hospital Clínico San Carlos, c/Profesor Martín Lagos s/n, Madrid 28040, Spain. pilar_garre@hotmail.com
Telephone: +34-913-303348 Fax: +34-913-302494
Received: April 17, 2019
Peer-review started: April 18, 2019
First decision: July 31, 2019
Revised: August 18, 2019
Accepted: October 14, 2019
Article in press: October 14, 2019
Published online: December 15, 2019
Abstract

Adenomatous polyposis (AP) is classified according to cumulative adenoma number in classical AP (CAP) and attenuated AP (AAP). Genetic susceptibility is the major risk factor in CAP due to mutations in the known high predisposition genes APC and MUTYH. However, the contribution of genetic susceptibility to AAP is lower and less understood. New predisposition genes have been recently proposed, and some of them have been validated, but their scarcity hinders accurate risk estimations and prevalence calculations. AAP is a heterogeneous condition in terms of severity, clinical features and heritability. Therefore, clinicians do not have strong discriminating criteria for the recommendation of the genetic study of known predisposition genes, and the detection rate is low. Elucidation and knowledge of new AAP high predisposition genes are of great importance to offer accurate genetic counseling to the patient and family members. This review aims to update the genetic knowledge of AAP, and to expound the difficulties involved in the genetic analysis of a highly heterogeneous condition such as AAP.

Keywords: Attenuated adenomatous polyposis, Genetic susceptibility, High predisposition gene, Genetic heterogeneity, Colorectal cancer

Core tip: Attenuated adenomatous polyposis (AAP) is a highly genetically and clinically heterogeneous condition in terms of severity, clinical features, heritability, and genetics. The major high predisposition genes APC and MUTYH explain a small fraction of AAP (10%-20%). Several predisposition genes have been recently proposed, and some of them have been validated, but studies addressing their global contribution to AAP genetic predisposition is scarce. Clinicians do not have strong discriminating criteria for the recommendation of genetic testing, and the detection rate is low. Therefore, multigene panel testing and a redefinition of strong clinical criteria could improve the outcome of AAP genetic testing.