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Journal of Pediatric Genetics Jun 2016Familial adenomatous polyposis (FAP), caused by a germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5q21, is an autosomal dominant disorder... (Review)
Review
Familial adenomatous polyposis (FAP), caused by a germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5q21, is an autosomal dominant disorder characterized by hundreds to thousands of adenomas throughout the gastrointestinal tract. A variety of extraintestinal manifestations, including thyroid, soft tissue, and brain tumors, may also be present. These patients inevitably develop colorectal carcinoma by the fourth decade of life. In this review, the pathology, epidemiology, and genetic features of FAP are discussed.
PubMed: 27617147
DOI: 10.1055/s-0036-1579760 -
The British Journal of Surgery May 2024Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of...
Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.
BACKGROUND
Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers.
METHODS
A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%).
RESULTS
One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes.
CONCLUSION
These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.
Topics: Humans; Adenomatous Polyposis Coli; Stomach Neoplasms; Adenocarcinoma; DNA Glycosylases; Neoplastic Syndromes, Hereditary; Europe; Adenomatous Polyps; Polyps
PubMed: 38722804
DOI: 10.1093/bjs/znae070 -
The Korean Journal of Gastroenterology... Dec 2018Although small bowel the mainly occupies the most part of the gastrointestinal tract, small intestine tumors are rare, insidious in clinical presentation, and frequently... (Review)
Review
Although small bowel the mainly occupies the most part of the gastrointestinal tract, small intestine tumors are rare, insidious in clinical presentation, and frequently represent a diagnostic and management challenge. Small bowel tumors are generally classified as epithelial, mesenchymal, lymphoproliferative, or metastatic. Familial adenomatous polyposis and Peutz-Jeghers syndrome are the most common inherited intestinal polyposis syndromes. Until the advent of capsule endoscopy (CE) and device-assisted enteroscopy (DAE) coupled with the advances in radiology, physicians had limited diagnostic examination for small bowel examination. CE and new radiologic imaging techniques have made it easier to detect small bowel tumors. DAE allows more diagnosis and deeper reach in small intestine. CT enteroclysis/CT enterography (CTE) provides information about adjacent organs as well as pictures of the intestinal lumen side. Compared to CTE, Magnetic resonance enteroclysis/enterography provides the advantage of soft tissue contrast and multiplane imaging without radiation exposure. Treatment and prognosis are tailored to each histological subtype of tumors.
Topics: Adenocarcinoma; Adenomatous Polyposis Coli; Capsule Endoscopy; Humans; Intestinal Neoplasms; Intestinal Polyps; Magnetic Resonance Imaging; Peutz-Jeghers Syndrome
PubMed: 30642146
DOI: 10.4166/kjg.2018.72.6.277 -
World Journal of Gastroenterology Nov 2011Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk... (Review)
Review
Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome.
Topics: Bone Morphogenetic Protein Receptors, Type I; Colon; Colorectal Neoplasms; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Intestinal Polyposis; Neoplastic Syndromes, Hereditary; Polyps; Rectum; Smad4 Protein
PubMed: 22171123
DOI: 10.3748/wjg.v17.i44.4839 -
Gastroenterology Report 2023Bone morphogenetic protein receptor type 1A () is responsible for two individual Mendelian diseases: juvenile polyposis syndrome and hereditary mixed polyposis syndrome...
BACKGROUND
Bone morphogenetic protein receptor type 1A () is responsible for two individual Mendelian diseases: juvenile polyposis syndrome and hereditary mixed polyposis syndrome 2, which have overlapping phenotypes. This study aimed to elucidate whether these two syndromes are just two subtypes of a single syndrome rather than two isolated syndromes.
METHODS
We sequenced the gene in 186 patients with polyposis and colorectal cancer, and evaluated the clinicopathological features and phenotypes of the probands and their available relatives with mutations.
RESULTS
germline mutations were found in six probands and their three available relatives. The numbers of frameshift, nonsense, splice-site, and missense mutations were one, one, two, and two, respectively; two of the six mutations were novel. Typical juvenile polyps were found in only three patients. Two patients had colorectal cancer rather than any polyps.
CONCLUSIONS
Diseases in germline mutation carriers vary from mixed polyposis to sole colorectal cancer, and typical juvenile polyps do not always occur in these carriers. The variety of phenotypes reflected the features of -mutation carriers, which should be recognized as a spectrum of one syndrome. Genetic testing may be a good approach to identifying -related syndromes.
PubMed: 36632626
DOI: 10.1093/gastro/goac082 -
Best Practice & Research. Clinical... 2009A multimodal approach of complementary techniques targeting primarily truncating, deletion and rearrangement mutations provides a robust screening protocol that... (Review)
Review
A multimodal approach of complementary techniques targeting primarily truncating, deletion and rearrangement mutations provides a robust screening protocol that identifies the vast majority of pathogenic germline APC gene mutations in FAP patients. Patients in whom no mutation is identified through this mutation protocol, may be sub-cohorts representing a different FAP pathogenesis including MYH associated polyposis and somatic cell mosaicism for APC gene mutations.
Topics: Adenomatous Polyposis Coli; DNA Glycosylases; DNA Mutational Analysis; Gene Expression Regulation, Neoplastic; Genes, APC; Genetic Predisposition to Disease; Genetic Testing; Human Genome Project; Humans; Mosaicism; Mutation; Predictive Value of Tests
PubMed: 19414146
DOI: 10.1016/j.bpg.2009.02.010 -
The Surgical Clinics of North America Oct 2015Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. About 30% of patients with CRC... (Review)
Review
Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death in men and women in the United States. About 30% of patients with CRC report a family history of CRC. However, only 5% of CRCs arise in the setting of a well-established mendelian inherited disorder. In addition, serrated polyposis is a clinically defined syndrome with multiple serrated polyps in the colorectum and an increased CRC risk for which the genetics are unknown. This article focuses on genetic and clinical aspects of Lynch syndrome, familial adenomatous polyposis, and MUTYH-associated polyposis.
Topics: Adenomatous Polyposis Coli; Biomarkers, Tumor; Colorectal Neoplasms, Hereditary Nonpolyposis; Early Detection of Cancer; Genetic Predisposition to Disease; Humans
PubMed: 26315524
DOI: 10.1016/j.suc.2015.05.004 -
Internal Medicine (Tokyo, Japan) Sep 2023A 36-year-old man was diagnosed with multiple gastric polyps by esophagogastroduodenoscopy. Subsequent colonoscopy identified two tubular adenomas, and computed...
A 36-year-old man was diagnosed with multiple gastric polyps by esophagogastroduodenoscopy. Subsequent colonoscopy identified two tubular adenomas, and computed tomography revealed subcutaneous tumors. Based on these findings, we suspected that gastric polyposis was associated with the APC gene, either attenuated familial adenomatous polyposis (AFAP) or gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). A genetic analysis demonstrated that he had a frameshift variant at codon 1928 of APC, suggesting AFAP. In this era of less Helicobacter pylori infection and frequent use of proton pump inhibitors, diagnoses of AFAP and GAPPS should be considered in patients with prominent gastric fundic gland polyposis.
Topics: Male; Humans; Adult; Helicobacter Infections; Helicobacter pylori; Adenomatous Polyposis Coli; Stomach Neoplasms
PubMed: 36725040
DOI: 10.2169/internalmedicine.1101-22 -
Clinics in Colon and Rectal Surgery Nov 2023The pathogenesis, clinical phenotype, treatment strategy, and family management of hereditary tumor syndromes are different from those of sporadic tumors. Nearly a... (Review)
Review
The pathogenesis, clinical phenotype, treatment strategy, and family management of hereditary tumor syndromes are different from those of sporadic tumors. Nearly a quarter of patients with colorectal cancer show significant familial aggregation and genetic predisposition, and 5 to 10% are associated with definite genetic factors. According to the clinical phenotype, it can be divided into nonpolyposis syndrome and polyposis syndrome. Among the polyposis syndrome patients with definite clinical symptoms, there are still some patients with unknown etiology (especially attenuated familial adenomatous polyposis), which is a difficult problem in clinical diagnosis and treatment. Therefore, for this rare disease, it is urgent to carry out multicenter studies, complete the gene variation spectrum, explore new pathogenic factors, and accumulate clinical experience. This article mainly introduces the research progress and related work of colorectal polyposis syndrome in China.
PubMed: 37795462
DOI: 10.1055/s-0043-1767708 -
Hereditary Cancer in Clinical Practice 2017Colorectal cancer (CRC) is one of the most common forms of cancer worldwide and familial adenomatous polyposis (FAP) accounts for approximately 1% of all CRCs.... (Review)
Review
Colorectal cancer (CRC) is one of the most common forms of cancer worldwide and familial adenomatous polyposis (FAP) accounts for approximately 1% of all CRCs. Adenomatous polyposis syndromes can be divided into; familial adenomatous polyposis (FAP) - classic FAP and attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), NTHL1-associated polyposis (NAP) and polymerase proofreading-associated polyposis (PPAP). The polyposis syndromes genetics and clinical manifestation of disease varies and cases with clinical diagnosis of FAP might molecularly show a different diagnosis. This review examines different aspects of the adenomatous polyposis syndromes genetics and clinical manifestation of disease; in addition the genotype-phenotype and modifier alleles of FAP will be discussed. New technology has made it possible to diagnose some of the mutation negative patients into their respective syndromes. There still remain many molecularly undiagnosed adenomatous polyposis patients indicating that there remain causative genes to be discovered and with today's technology these are expected to be identified in the near future. The knowledge about the role of modifier alleles in FAP will contribute to improved pre-symptomatic diagnosis and treatment. New novel mutations will continually be discovered in genes already associated with disease and new genes will be discovered that are associated with adenomatous polyposis. The search for modifier alleles in FAP should be made a priority.
PubMed: 28331556
DOI: 10.1186/s13053-017-0065-x