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Gorji L, Albrecht P. Hamartomatous polyps: Diagnosis, surveillance, and management. World J Gastroenterol 2023; 29:1304-1314. [PMID: 36925460 PMCID: PMC10011967 DOI: 10.3748/wjg.v29.i8.1304] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/08/2022] [Accepted: 02/16/2023] [Indexed: 02/28/2023] Open
Abstract
Hereditary polyposis syndrome can be divided into three categories: Ade-nomatous, serrated, and hamartomatous polyps. Hamartomatous polyps, malformations of normal tissue presenting in a disorganized manner, are characterized by an autosomal dominant inheritance pattern. These syndromes exhibit hamartomatous gastrointestinal polyps in conjunction to extra-intestinal manifestations, which require conscientious and diligent monitoring. Peutz-Jeghers syndrome, Cowden syndrome, and juvenile polyposis syndrome are the most common displays of hamartomatous polyposis syndrome (HPS). Diagnosis can be pursued with molecular testing and endoscopic sampling. Early identification of these autosomal dominant pathologies allows to optimize malignancy sur-veillance, which helps reduce morbidity and mortality in both the affected patient population as well as at-risk family members. Endoscopic surveillance is an important pillar of prognosis and monitoring, with many patients eventually requiring surgical intervention. In this review, we discuss the diagnosis, surveillance, and management of HPS.
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Affiliation(s)
- Leva Gorji
- Department of Surgery, Kettering Health Dayton, Dayton, OH 45405, United States
| | - Peter Albrecht
- Department of Surgery, Kettering Health Dayton, Dayton, OH 45405, United States
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Strong Hereditary Predispositions to Colorectal Cancer. Genes (Basel) 2022; 13:genes13122326. [PMID: 36553592 PMCID: PMC9777620 DOI: 10.3390/genes13122326] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 12/01/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
Cancer is one of the most common causes of death worldwide. A strong predisposition to cancer is generally only observed in colorectal cancer (5% of cases) and breast cancer (2% of cases). Colorectal cancer is the most common cancer with a strong genetic predisposition, but it includes dozens of various syndromes. This group includes familial adenomatous polyposis, attenuated familial adenomatous polyposis, MUTYH-associated polyposis, NTHL1-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, Lynch syndrome, and Muir-Torre syndrome. The common symptom of all these diseases is a very high risk of colorectal cancer, but depending on the condition, their course is different in terms of age and range of cancer occurrence. The rate of cancer development is determined by its conditioning genes, too. Hereditary predispositions to cancer of the intestine are a group of symptoms of heterogeneous diseases, and their proper diagnosis is crucial for the appropriate management of patients and their successful treatment. Mutations of specific genes cause strong colorectal cancer predispositions. Identifying mutations of predisposing genes will support proper diagnosis and application of appropriate screening programs to avoid malignant neoplasm.
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Dal Buono A, Gaiani F, Poliani L, Laghi L. Juvenile polyposis syndrome: An overview. Best Pract Res Clin Gastroenterol 2022; 58-59:101799. [PMID: 35988962 DOI: 10.1016/j.bpg.2022.101799] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 03/13/2022] [Accepted: 03/23/2022] [Indexed: 01/31/2023]
Abstract
Juvenile polyposis syndrome (JPS) is a rare precancerous condition that confers an increased risk of developing gastrointestinal cancers. The inheritance pattern is autosomal dominant. JPS should be clinically suspected when the other hamartomatous polyposis syndromes are excluded (i.e., Peutz- Jeghers and Cowden), in presence of numerous juvenile polyps in the colorectum or in other GI locations. Among the syndromic features, JPS can present with concomitant extra-intestinal manifestations, above all cutaneous manifestations such as telangiectasia, pigmented nevi, and skeletal stigmata. Pathogenic germline variants of either BMPR1A or SMAD4 cause the syndrome. In JPS a cumulative risk of CRC of 39-68% has been estimated. The oncological risk justifies and imposes prevention strategies that aim at the cancer risk reduction through endoscopic screening, as recommended by international scientific societies. The aim of this review is to summarize clinical and genetic features of JPS and to elucidate the steps of the clinical management from diagnosis to surveillance.
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Affiliation(s)
- Arianna Dal Buono
- Division of Gastroenterology, Department of Gastroenterology, Humanitas Research Hospital - IRCCs, Rozzano, Milan, Italy
| | - Federica Gaiani
- Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Laura Poliani
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Luigi Laghi
- Department of Medicine and Surgery, University of Parma, Parma, Italy; Laboratory of Molecular Gastroenterology, Humanitas Clinical and Research Centre, Rozzano, Milan, Italy.
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Monahan KJ, Bradshaw N, Dolwani S, Desouza B, Dunlop MG, East JE, Ilyas M, Kaur A, Lalloo F, Latchford A, Rutter MD, Tomlinson I, Thomas HJW, Hill J. Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG). Gut 2020; 69:411-444. [PMID: 31780574 PMCID: PMC7034349 DOI: 10.1136/gutjnl-2019-319915] [Citation(s) in RCA: 290] [Impact Index Per Article: 58.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 10/25/2019] [Accepted: 11/05/2019] [Indexed: 12/12/2022]
Abstract
Heritable factors account for approximately 35% of colorectal cancer (CRC) risk, and almost 30% of the population in the UK have a family history of CRC. The quantification of an individual's lifetime risk of gastrointestinal cancer may incorporate clinical and molecular data, and depends on accurate phenotypic assessment and genetic diagnosis. In turn this may facilitate targeted risk-reducing interventions, including endoscopic surveillance, preventative surgery and chemoprophylaxis, which provide opportunities for cancer prevention. This guideline is an update from the 2010 British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland (BSG/ACPGBI) guidelines for colorectal screening and surveillance in moderate and high-risk groups; however, this guideline is concerned specifically with people who have increased lifetime risk of CRC due to hereditary factors, including those with Lynch syndrome, polyposis or a family history of CRC. On this occasion we invited the UK Cancer Genetics Group (UKCGG), a subgroup within the British Society of Genetic Medicine (BSGM), as a partner to BSG and ACPGBI in the multidisciplinary guideline development process. We also invited external review through the Delphi process by members of the public as well as the steering committees of the European Hereditary Tumour Group (EHTG) and the European Society of Gastrointestinal Endoscopy (ESGE). A systematic review of 10 189 publications was undertaken to develop 67 evidence and expert opinion-based recommendations for the management of hereditary CRC risk. Ten research recommendations are also prioritised to inform clinical management of people at hereditary CRC risk.
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Affiliation(s)
- Kevin J Monahan
- Family Cancer Clinic, St Mark's Hospital, London, UK
- Faculty of Medicine, Imperial College, London, UK
| | - Nicola Bradshaw
- Clinical Genetics, West of Scotland Genetics Services, Glasgow, Glasgow, UK
| | - Sunil Dolwani
- Gastroenterology, Cardiff and Vale NHS Trust, Cardiff, UK
| | - Bianca Desouza
- Clinical Genetics, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - James E East
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
- Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK
| | - Mohammad Ilyas
- Faculty of Medicine & Health Sciences, Nottingham University, Nottingham, UK
| | - Asha Kaur
- Head of Policy and Campaigns, Bowel Cancer UK, London, UK
| | - Fiona Lalloo
- Genetic Medicine, Central Manchester University Hospitals Foundation Trust, Manchester, UK
| | | | - Matthew D Rutter
- Gastroenterology, University Hospital of North Tees, Stockton-on-Tees, UK
- Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK
| | - Ian Tomlinson
- Nuffield Department of Clinical Medicine, Wellcome Trust Centre for Human Genetics, Birmingham, UK
- Cancer Research Centre, University of Edinburgh, Edinburgh, UK
| | - Huw J W Thomas
- Family Cancer Clinic, St Mark's Hospital, London, UK
- Faculty of Medicine, Imperial College, London, UK
| | - James Hill
- Genetic Medicine, Central Manchester University Hospitals Foundation Trust, Manchester, UK
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Management of Juvenile Polyposis Syndrome in Children and Adolescents: A Position Paper From the ESPGHAN Polyposis Working Group. J Pediatr Gastroenterol Nutr 2019; 68:453-462. [PMID: 30585890 DOI: 10.1097/mpg.0000000000002246] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Polyposis Working Group developed recommendations to assist clinicians and health care providers with appropriate management of patients with juvenile polyposis. This is the first juvenile polyposis Position Paper published by ESPGHAN with invited experts. Many of the published studies were descriptive and/or retrospective in nature, consequently after incorporating a modified version of the GRADE system many of the recommendations are based on expert opinion. This ESPGHAN Position Paper provides a guide for diagnosis, assessment, and management of juvenile polyposis syndrome in children and adolescents, and will be helpful in the appropriate management and timing of procedures in children and adolescents. The formation of international collaboration and consortia is proposed to monitor patients prospectively to advance our understanding of juvenile polyposis conditions.
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Abstract
Colorectal cancer (CRC) is a major cause of morbidity and mortality in the world. Up to 30 % of CRCs have evidence of a familial component, and about 5 % are thought to be due to well-characterized inherited mutations. This review will focus on recent developments in the understanding of the individual hereditary CRC syndromes, including Lynch syndrome, familial CRC type X, familial adenomatous polyposis, MutYH-associated polyposis, Peutz-Jeghers syndrome, juvenile polyposis syndrome, PTEN hamartomatous syndrome, and serrated polyposis syndrome. Advances within the area of hereditary colon cancer syndromes paint a picture of a rapidly moving, rapidly maturing, and increasingly collaborative field with many opportunities for ongoing research and development.
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Brosens LAA, Langeveld D, Hattem WAV, Giardiello FM, Offerhaus GJA. Juvenile polyposis syndrome. World J Gastroenterol 2011; 17:4839-44. [PMID: 22171123 PMCID: PMC3235625 DOI: 10.3748/wjg.v17.i44.4839] [Citation(s) in RCA: 106] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2011] [Revised: 06/09/2011] [Accepted: 06/16/2011] [Indexed: 02/06/2023] Open
Abstract
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.
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Damnacanthal, a noni component, exhibits antitumorigenic activity in human colorectal cancer cells. J Nutr Biochem 2011; 23:915-23. [PMID: 21852088 DOI: 10.1016/j.jnutbio.2011.04.017] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2010] [Revised: 04/19/2011] [Accepted: 04/21/2011] [Indexed: 01/04/2023]
Abstract
Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases including cancer. Although noni has been consumed for a long time in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In this report, we examined systematic approaches on the cancer-suppressing capability of damnacanthal in colorectal tumorigenesis. Damnacanthal exhibits cell growth arrest as well as caspase activity induction in colorectal cancer cells. We also examined several potential target proteins and found that the proapoptotic protein nonsteroidal anti-inflammatory activated gene-1 (NAG-1) is highly induced. Subsequently, we have found that damnacanthal also enhances transcription factor CCAAT/enhancer binding protein β (C/EBPβ), which controls NAG-1 transcriptional activity. Blocking of C/EBPβ by shRNA results in the reduction of NAG-1 expression as well as caspase activity in the presence of damnacanthal. Taken together, these results indicate that damnacanthal increases antitumorigenic activity in human colorectal cancer cells and that C/EBPβ plays a role in damnacanthal-induced NAG-1 expression.
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Duggan S, Prichard D, Kirca M, Kelleher D. Inherited Syndromes Predisposing to Inflammation and GI Cancer. Recent Results Cancer Res 2011; 185:35-50. [PMID: 21822818 DOI: 10.1007/978-3-642-03503-6_2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cancers arising within the gastrointestinal (GI) tract are commonly associated with an immune component at their inception and later in their maintenance. While many of the immune factors and immune cell types surrounding these lesions have been highlighted, the underlying pre-dispositions in immunesupported carcinogenesis are not well characterised. Inherited Mendelian GI disorders such as polyposis syndromes, while classically due to germline mutations in non-immune genes, commonly demonstrate alterations in key immune and inflammatory genes. In some cases immune based therapies have been shown to provide at least some benefit in animal models of these syndromes. The advent of genome wide association studies has begun to powerfully examine the genetic nature of complex non-Mendelian GI diseases highlighting polymorphisms within immune related genes and their potential to provide the niche in which GI cancers may originate. Here in the role in which Mendelian and non-Mendelian genetics of immune related factors supporting GI malignancy will be presented and discussed.
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Affiliation(s)
- Shane Duggan
- Department of Clinical Medicine and Institute of Molecular Medicine, Trinity College Dublin, Ireland
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Abstract
Colorectal cancer is one of the most common digestive malignant tumors in China. Its incidence and mortality rates rank top among all malignant tumors. Previous studies show that nearly one-third of colorectal cancers are associated with hereditary colorectal tumors. Hereditary colorectal tumors are mainly divided into two categories: hereditary nonpolyposis colorectal cancer and hereditary colorectal polyposis. In this article, we will review the recent advances in research on hereditary colorectal neoplasms.
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