Major Hereditary Gastrointestinal Cancer Syndromes: a Narrative Review

2017 ◽  
Vol 26 (2) ◽  
pp. 157-163 ◽  
Author(s):  
Lakshmi Manogna Chintalacheruvu ◽  
Trudy Shaw ◽  
Avanija Buddam ◽  
Osama Diab ◽  
Thamer Kassim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Genetic Testing ◽  
Gastrointestinal Cancer ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Clinical Manifestations ◽  
Micro Rna ◽  
Diffuse Gastric Cancer ◽  
Adenomatous Polyposis ◽  
Cancer Syndromes

Gastrointestinal cancer is one of the major causes of death worldwide. Hereditary gastrointestinal cancer syndromes constitute about 5-10% of all cancers. About 20-25% of undiagnosed cases have a possible hereditary component, which is not yet established. In the last few decades, the advance in genomics has led to the discovery of multiple cancer predisposition genes in gastrointestinal cancer. Physicians should be aware of these syndromes to identify high-risk patients and offer genetic testing to prevent cancer death. In this review, we describe clinical manifestations, genetic testing and its challenges, diagnosis and management of the major hereditary gastrointestinal cancer syndromes.Key words:  −  −  −  − .Abbreviations: ACG: American College of Gastroenterology; AFAP: attenuated FAP; APC: adenomatous polyposis coli; CDH1: E-cadherin; CHRPE: congenital hypertrophy of the retinal pigment epithelium; CRC: colorectal cancer; FAMMM: Familial atypical multiple mole melanoma; FAP: Familial adenomatous polyposis; GC: gastric cancer; HDGC: Hereditary diffuse gastric cancer; IHC: immunohistochemical; IPAA: ileal pouch–anal anastomosis; IRA: ileorectal anastomosis; MSI: microsatellite instability; MMR: mismatch repair; miRNA: micro RNA.

scholarly journals Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis

2014 ◽  
Vol 307 (1) ◽  
pp. G16-G23 ◽  
Author(s):  
Anne E. Powell ◽  
Gregory Vlacich ◽  
Zhen-Yang Zhao ◽  
Eliot T. McKinley ◽  
M. Kay Washington ◽  
...  
Keyword(s):  
Familial Adenomatous Polyposis ◽  
Progenitor Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Tumor Formation ◽  
Therapeutic Interventions ◽  
Adenomatous Polyposis ◽  
Extracolonic Manifestations ◽  
Predictable Pattern ◽  
Leucine Rich Repeats

Individuals with familial adenomatous polyposis (FAP) harbor a germline mutation in adenomatous polyposis coli ( APC). The major clinical manifestation is development of multiple colonic tumors at a young age due to stochastic loss of the remaining APC allele. Extracolonic features, including periampullary tumors, gastric abnormalities, and congenital hypertrophy of the retinal pigment epithelium, may occur. The objective of this study was to develop a mouse model that simulates these features of FAP. We combined our Lrig1-CreERT2/+ mice with Apcfl/+ mice, eliminated one copy of Apc in leucine-rich repeats and immunoglobulin-like domains protein 1 (Lrig1)-positive (Lrig1+) progenitor cells with tamoxifen injection, and monitored tumor formation in the colon by colonoscopy and PET. Initial loss of one Apc allele in Lrig1+ cells results in a predictable pattern of preneoplastic changes, culminating in multiple distal colonic tumors within 50 days of induction, as well as the extracolonic manifestations of FAP mentioned above. We show that tumor formation can be monitored by noninvasive PET imaging. This inducible stem cell-driven model recapitulates features of FAP and offers a tractable platform on which therapeutic interventions can be monitored over time by colonoscopy and noninvasive imaging.

Congenital Hypertrophy of the Retinal Pigment Epithelium in Familial Adenomatous Polyposis

Ophthalmology ◽  
1989 ◽  
Vol 96 (6) ◽  
pp. 879-884 ◽  
Author(s):  
Anthony Romania ◽  
Z. Nicholas Zakov ◽  
Ellen McGannon ◽  
Thomas Schroeder ◽  
Francoise Heyen ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Familial Adenomatous Polyposis ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Adenomatous Polyposis ◽  
Congenital Hypertrophy

Multiple Approach to the Exploration of Genotype-Phenotype Correlations in Familial Adenomatous Polyposis

2003 ◽  
Vol 21 (9) ◽  
pp. 1698-1707 ◽  
Author(s):  
L. Bertario ◽  
A. Russo ◽  
P. Sala ◽  
L. Varesco ◽  
M. Giarola ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Familial Adenomatous Polyposis ◽  
Multiple Correspondence Analysis ◽  
Retinal Pigment ◽  
Clinical Manifestations ◽  
Apc Gene ◽  
Adenomatous Polyposis ◽  
Mutation Site ◽  
Cancer Predisposition Syndrome ◽  
Increased Risk

Purpose: Familial adenomatous polyposis (FAP), caused by a mutation in the APC gene, is a colorectal cancer predisposition syndrome associated with several other clinical conditions. The severity of the FAP is related to the position of the inherited mutation in the APC gene. We analyzed a large series of FAP patients to identify associations among major clinical manifestations and to correlate the mutation site with specific disease manifestations. Materials and Methods: APC mutations were identified in 953 FAP patients from 187 families. We used unconditional logistic regression models and a method involving generalized estimating equations to investigate the association between genotype and phenotype. We used multiple correspondence analysis to represent the interrelationships of a multiway contingency table of the considered variables. Results: APC germline mutations were located between codons 156 and 2011 of the APC gene. Mutations spanning the region between codons 543 and 1309 were variable, but strongly associated with congenital hypertrophy of retinal pigment epithelium. Mutations between codons 1310 and 2011 were associated with a six-fold risk of desmoid tumors relative to the low-risk reference region (159 to 495). Mutations at codon 1309 were associated with early development of colorectal cancer. Mutations between codons 976 and 1067 were associated with a three- to four-fold increased risk of duodenal adenomas. The cumulative frequency of extracolonic manifestations was highest for mutations between codons 976 and 1067, followed by mutations between 1310 and 2011. Conclusion: Analysis of the relation between APC mutation site and phenotype identifies subgroups of FAP patients at high risk for major extracolonic disease, which is useful for surveillance and prevention.

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