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Hisada I, Yamaji T, Sawada N, Inoue M, Tsugane S, Iwasaki M. Association of plasma branched-chain amino acid levels with colorectal cancer risk in a nested case-control study. Jpn J Clin Oncol 2025; 55:334-340. [PMID: 39673725 DOI: 10.1093/jjco/hyae172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 11/25/2024] [Indexed: 12/16/2024] Open
Abstract
BACKGROUND Intake of branched-chain amino acids (BCAA) has been suggested to have a prophylactic effect against carcinogenesis in colorectal cancer (CRC). However, the possible effect of plasma BCAA concentration has not been fully evaluated. METHODS We conducted a prospective case-control study within a cohort of four public health center areas for which blood sample and questionnaire data from a 5-year follow-up survey were available. We identified 360 newly diagnosed CRC cases during the follow-up period and selected two matched controls for each case. We estimated odds ratio (OR) and 95% confidence intervals (CI) for CRC using conditional logistic regression models adjusted for potential confounding factors. RESULTS Increased plasma concentrations of BCAAs were not inversely associated with CRC risk after adjustment for potential confounders. Compared with the lowest quartile, ORs in the highest quartile of leucine, isoleucine, valine, and total BCAA were 0.74 (95% CI, 0.49-1.12), 0.85 (0.56-1.29), 0.75 (0.50-1.13), and 0.70 (0.47-1.05), respectively. After excluding cases diagnosed within the first 6 years of follow-up, total BCAA and leucine were significantly related to a decreased risk of CRC, with ORs in the highest quartile of total BCAA and leucine of 0.58 (0.35-0.96) and 0.56 (0.33-0.93), respectively. CONCLUSIONS We found no statistically significant inverse association between plasma BCAA concentrations and CRC risk in overall analyses, whereas on 6-year exclusion, total BCAA and leucine were associated with decreased CRC risk. Plasma BCAA concentrations may play a prophylactic role in colorectal carcinogenesis, and further investigation is warranted.
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Affiliation(s)
- Izumi Hisada
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Cancer Medicine, Cooperative Graduate Program, The Jikei University Graduate School of Medicine, Tokyo, Japan
| | - Taiki Yamaji
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Norie Sawada
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Manami Inoue
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Division of Prevention, National Cancer Center Institute for Cancer Control, Tokyo, Japan
| | - Shoichiro Tsugane
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Graduate School of Public Health, International University of Health and Welfare, Tokyo, Japan
| | - Motoki Iwasaki
- Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan
- Cancer Medicine, Cooperative Graduate Program, The Jikei University Graduate School of Medicine, Tokyo, Japan
- Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan
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Wang H, Zhu W, Lei J, Liu Z, Cai Y, Wang S, Li A. Gut microbiome differences and disease risk in colorectal cancer relatives and healthy individuals. Front Cell Infect Microbiol 2025; 15:1573216. [PMID: 40196042 PMCID: PMC11973321 DOI: 10.3389/fcimb.2025.1573216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Accepted: 03/03/2025] [Indexed: 04/09/2025] Open
Abstract
Given the heightened focus on high-risk populations, this study aimed to provide insights into early susceptibility and preventive strategies for colorectal cancer (CRC) by focusing on high-risk populations. In this research, fecal samples from 1,647 individuals across three discovery cohorts and nine external validation cohorts were sequenced using whole-genome metagenomic sequencing. A prediction model based on random forest was constructed using the nine external cohorts and independently validated with the three discovery cohorts. A disease probability (POD) model based on microbial biomarkers was developed to assess CRC risk. We found that the gut microbiome composition of CRC relatives differed from that of controls, with enrichment of species such as Fusobacterium and Bacteroides and a reduction in beneficial genera like Coprococcus and Roseburia. Additionally, dietary red meat intake emerged as a risk factor. The POD model indicated an elevated risk of CRC in unaffected relatives. The findings suggest that the POD for CRC may be increased in unaffected relatives or individuals living in shared environments, although this difference did not reach statistical significance. Our study introduces a novel framework for assessing the risk of colorectal cancer in ostensibly healthy individuals.
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Affiliation(s)
- Huifen Wang
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Weiwei Zhu
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jun Lei
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zhibo Liu
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yudie Cai
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shuaifeng Wang
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ang Li
- Gene Hospital of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- State Key Laboratory of Antiviral Drugs, Zhengzhou University, Zhengzhou, China
- Academy of Medical Sciences, Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou University, Zhengzhou, China
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Maia B, Madeira E, Gadelha MR, Kasuki L. Assessment of the frequency and risk factors for colorectal cancer in acromegaly. Endocrine 2025; 87:1162-1170. [PMID: 39537960 DOI: 10.1007/s12020-024-04099-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024]
Abstract
INTRODUCTION Acromegaly is associated with a possible increased risk of neoplasias, like colorectal cancer (CRC), although magnitude of this risk is unclear. OBJECTIVES Evaluate frequency of colonic adenomatous polyps and CRC in patients with acromegaly at first and subsequent colonoscopies; correlate risk factors of CRC and disease activity of acromegaly with colonoscopy findings and analyze relationship of acromegaly as a risk factor for CRC and the best period for screening this neoplasia. METHODS Patients ≥18 years-old with acromegaly were included. A questionnaire involving characteristics of follow-up of acromegaly and risk factors of CRC was created. Biochemical and colonoscopic data were collected through medical records. Only full-length colonoscopies with satisfactory colonic preparation were included. RESULTS 123 patients (77 women) were included (mean age at diagnosis of 43.1 years and mean follow-up of 13.7 years). In baseline colonoscopy, 80.5% had non-neoplastic findings, 14.6% non-advanced adenomas, 3.3% advanced adenomas and 1.6% CRC. At end of the study, 3 (2.4%) patients were diagnosed with CRC. No patient under 50 years had a neoplastic lesion on colonoscopy. We observed a positive statistically significant relationship between smoking (p = 0.026), age at diagnosis of acromegaly (p < 0.001), age at baseline colonoscopy (p = 0.002), and risk of adenomas and/or CRC at initial colonoscopy. CONCLUSIONS Smoking and advanced age were positively related to a higher risk of developing premalignant/malignant colonic lesions. Age ( > 50 years) was the most robust variable. Our data suggest that screening age for CRC in acromegaly should be reviewed.
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Affiliation(s)
- B Maia
- Endocrine Unit and Neuroendocrinology Research Center, Medical School, and Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - E Madeira
- Gastroenterology Unit, Medical School, and Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
| | - M R Gadelha
- Endocrine Unit and Neuroendocrinology Research Center, Medical School, and Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
- Neuroendocrine Unit - Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
- Neuropathology and Molecular Genetic Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil
| | - L Kasuki
- Endocrine Unit and Neuroendocrinology Research Center, Medical School, and Hospital Universitário Clementino Fraga Filho - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
- Neuroendocrine Unit - Instituto Estadual do Cérebro Paulo Niemeyer, Secretaria Estadual de Saúde, Rio de Janeiro, Brazil.
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Khafaga DSR, Muteeb G, Aswa DW, Aatif M, Farhan M, Allam S. Green chemistry: Modern therapies using nanocarriers for treating rare brain cancer metastasis from colon cancer. SLAS DISCOVERY : ADVANCING LIFE SCIENCES R & D 2025; 31:100213. [PMID: 39826871 DOI: 10.1016/j.slasd.2025.100213] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/18/2024] [Accepted: 01/14/2025] [Indexed: 01/22/2025]
Abstract
Brain metastasis (BM) from colon cancer is associated with a poor prognosis and restricted treatment alternatives, largely due to issues related to blood-brain barrier (BBB) permeability and the negative effects of standard chemotherapy. Nanotechnology improves treatment efficacy by enabling targeted and controlled drug delivery. This review article evaluates the potential of nanotechnology-based therapies for treating colon cancer BM, emphasizing their capacity to cross the BBB, diminish metastatic growth, and enhance overall survival rates. A review of multiple studies evaluated nanoparticles (NPs) as carriers for chemotherapy, focusing on parameters including particle size, surface charge, and drug-loading capacity. The study also reviewed studies that examined BBB penetration, in vitro tumor accumulation, and in vivo tumor growth inhibition. In vitro findings indicated that NPs accumulate more efficiently in BM tissue than in healthy brain tissue and show significant BBB penetration. In vivo, nanotherapy markedly inhibited tumor growth and prolonged survival relative to conventional chemotherapy or control treatments while also exhibiting reduced side effects. Recent studies demonstrated that plant extracts can effectively and safely synthesize nanomaterials, positioning them as a viable and environmentally friendly precursor for nanomaterial production. Nanotechnology-based therapies demonstrate significant potential in the treatment of colon cancer BM by minimizing systemic toxicity, enhancing therapeutic efficacy, and facilitating more targeted drug delivery. Further research is required to confirm these findings and implement them in clinical practice.
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Affiliation(s)
- Doaa S R Khafaga
- Health Sector, Faculty of Science, Galala University, New Galala City 43511, Suez, Egypt.
| | - Ghazala Muteeb
- Department of Nursing, College of Applied Medical Sciences, King Faisal University, Al-Ahsa, Saudi Arabia.
| | - Darin W Aswa
- Faculty of Medicine, Galala University, New Galala City 43511, Suez, Egypt
| | - Mohammad Aatif
- Department of Public Health, College of Applied Medical Sciences, King Faisal University, Al-Ahsa 31982, Saudi Arabia
| | - Mohd Farhan
- Department of Basic Sciences, Preparatory Year, King Faisal University, Al-Ahsa 31982, Saudi Arabia; Department of Chemistry, College of Science, King Faisal University, Al Ahsa, 31982, Saudi Arabia
| | - Salma Allam
- Faculty of Medicine, Galala University, New Galala City 43511, Suez, Egypt
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Partyka O, Pajewska M, Czerw A, Deptała A, Mękal D, Sygit K, Kowalczyk D, Cipora E, Kaczmarski M, Gazdowicz L, Dykowska G, Sienkiewicz Z, Banaś T, Małecki K, Grochans E, Grochans S, Cybulska AM, Schneider-Matyka D, Bandurska E, Bandurski T, Drobnik J, Pobrotyn P, Marczak M, Kozlowski R. Current Progress in Clinical Research in Secondary Prevention and Early Detection of Colorectal Cancer. Cancers (Basel) 2025; 17:367. [PMID: 39941735 PMCID: PMC11816288 DOI: 10.3390/cancers17030367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 01/08/2025] [Accepted: 01/20/2025] [Indexed: 02/16/2025] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally. The risk of disease increases with age, as most CRC patients are over 50 years old. Due to the progressive aging of societies in high-income countries, the problem of CRC will increase. This makes the development of new early detection methods and the implementation of effective screening programs crucial. Key areas of focus include raising population awareness about the importance of screening, educating high-risk populations, and improving and developing early diagnostic methods. The primary goal of this review is to provide a concise overview of recent trends and progress in CRC secondary prevention based on available information from clinical trials.
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Affiliation(s)
- Olga Partyka
- Department of Health Economics and Medical Law, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Monika Pajewska
- Department of Health Economics and Medical Law, Medical University of Warsaw, 02-091 Warsaw, Poland
- Department of Economic and System Analyses, National Institute of Public Health NIH—National Research Institute, 00-791 Warsaw, Poland
| | - Aleksandra Czerw
- Department of Health Economics and Medical Law, Medical University of Warsaw, 02-091 Warsaw, Poland
- Department of Economic and System Analyses, National Institute of Public Health NIH—National Research Institute, 00-791 Warsaw, Poland
| | - Andrzej Deptała
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Dominika Mękal
- Department of Oncology Propaedeutics, Medical University of Warsaw, 01-445 Warsaw, Poland
| | - Katarzyna Sygit
- Faculty of Health Sciences, Calisia University, 62-800 Kalisz, Poland
| | - Dariusz Kowalczyk
- Faculty of Health Sciences, Calisia University, 62-800 Kalisz, Poland
| | - Elżbieta Cipora
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Mateusz Kaczmarski
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Lucyna Gazdowicz
- Medical Institute, Jan Grodek State University in Sanok, 38-500 Sanok, Poland
| | - Grażyna Dykowska
- Department of Health Economics and Medical Law, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Zofia Sienkiewicz
- Department of Nursing, Social and Medical Development, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Tomasz Banaś
- Department of Radiotherapy, Maria Sklodowska-Curie Institute-Oncology Centre, 31-115 Cracow, Poland
| | - Krzysztof Małecki
- Department of Radiotherapy for Children and Adults, University Children’s Hospital of Cracow, 30-663 Cracow, Poland
| | - Elżbieta Grochans
- Department of Nursing, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland
| | - Szymon Grochans
- Department of Clinical Nursing, Faculty of Health Sciences, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland
| | - Anna Maria Cybulska
- Department of Nursing, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland
| | - Daria Schneider-Matyka
- Department of Nursing, Pomeranian Medical University in Szczecin, 71-210 Szczecin, Poland
| | - Ewa Bandurska
- Center for Competence Development, Integrated Care and e-Health, Medical University of Gdansk, 80-204 Gdansk, Poland
| | - Tomasz Bandurski
- Division of Radiology Informatics and Statistics, Medical University of Gdansk, 80-210 Gdansk, Poland
| | - Jarosław Drobnik
- Department of Family Medicine, Faculty of Medicine, Wroclaw Medical University, 51-141 Wroclaw, Poland
| | - Piotr Pobrotyn
- Remedial Specialistic Clinic, “Pulsantis Sp. z o.o”, 53-238 Wroclaw, Poland
| | - Michal Marczak
- Department of Innovation, Merito University in Poznan, 61-895 Poznan, Poland
| | - Remigiusz Kozlowski
- Department of Management and Logistics in Healthcare, Medical University of Lodz, 90-131 Lodz, Poland
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Parra-Izquierdo V, Otero-Regino W, Juliao-Baños F, Frías-Ordoñez JS, Ibañez-Pinilla E, Gil-Parada FL, Marulanda-Fernández H, Otero-Parra L, Otero-Ramos E, Puentes-Manosalva FE, Guzmán Rojas GA, Ernest-Suárez K, Villa-Ovalles K, Paredes-Mendez JE, Jara-Alba ML, Andrade-Zamora D, Ardila-Báez MA, Flórez-Sarmiento C, Veitia G, Sánchez A, Arango-Molano LA, Fluxa F, Freitas Queiroz NS, Serrano M. Dysplasia and Colorectal Cancer Surveillance in Ulcerative Colitis Patients in Latin America: Real-World Data. CROHN'S & COLITIS 360 2025; 7:otae081. [PMID: 39834355 PMCID: PMC11744193 DOI: 10.1093/crocol/otae081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Indexed: 01/22/2025] Open
Abstract
Background The prevalence of colorectal cancer (CRC) in patients with ulcerative colitis (UC) is higher than in the general population, in Latin America there is a progressive increase of UC, and information about CRC screening in inflammatory bowel disease (IBD) is scarce. The aim of this study was to analyze the findings of endoscopic surveillance of CRC in patients with IBD according to available technology. Methods Multicenter, cross-sectional, analytical study conducted in Latin American countries, in patients with UC, predominantly with more than 8 years of diagnosis and different degrees of disease activity. Surveillance colonoscopies were performed according to available technology. Risk factors for dysplasia detection were analyzed. Results One hundred and forty-four patients, 55.5% women, mean age 47.3 (range 17.1 to 90; SD 15.64) years and mean duration of disease 12.71 (range 0.64 to 57.13; SD 8.08) years. Forty-nine lesions were identified, 18 corresponded to dysplasia. The detection rate of dysplasia per lesion and per procedure was 36.7% and 12.5%, respectively. By logistic regression analysis, the duration of disease (OR 1.12;95%CI:1.047 to 1.215, P = .002) and the presence of post-inflammatory polyps (OR 3.4;95%CI:1.11 to 10.36, P = .031) were risk factors for higher detection of dysplasia. Digital chromoendoscopy was associated with greater detection of dysplasia (OR 4.99, 95%CI: 1.092 to 22.864, P = .038). Conclusions In our region, the duration of disease and the presence of post-inflammatory polyps were the factors with the highest association for dysplasia detection, and digital chromoendoscopy with directed biopsies was the technique of choice. The implementation of a specific surveillance program in colonoscopy in IBD is an effective strategy to achieve high detection rates.
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Affiliation(s)
- Viviana Parra-Izquierdo
- Gastroenterology and Rheumatology, International Hospital of Colombia, Bucaramanga, Colombia
- Cellular and Molecular Immunology Group (INMUBO), Universidad El Bosque, Bogotá, Colombia
| | - William Otero-Regino
- Gastroenterology, National University of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, National University Hospital of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, Gastroenterology and Endoscopy Center, Bogota, Colombia
| | | | - Juan Sebastián Frías-Ordoñez
- Gastroenterology, National University of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, National University Hospital of Colombia, Bogota, Colombia
| | | | | | - Hernando Marulanda-Fernández
- Gastroenterology, National University of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, National University Hospital of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, Gastroenterology and Endoscopy Center, Bogota, Colombia
- Central Police Hospital, Bogota, Colombia
| | - Lina Otero-Parra
- Gastroenterology, National University of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, Gastroenterology and Endoscopy Center, Bogota, Colombia
| | - Elder Otero-Ramos
- Gastroenterology and Digestive Endoscopy, Gastroenterology and Endoscopy Center, Bogota, Colombia
- Central Police Hospital, Bogota, Colombia
| | | | - Gerardo Andrés Guzmán Rojas
- Gastroenterology, Farallones Clinic, Cali, Valle del Cauca, Colombia
- Gastroenterology, Colsanitas Chipi Chape Medical Center Cali, Valle del Cauca, Colombia
| | - Kenneth Ernest-Suárez
- School of Medicine, University of Costa Rica, San José, Costa Rica
- Inflammatory Bowel Disease Unit, Hospital México, Caja Costarricense de Seguro Social, San José, Costa Rica
| | - Keyla Villa-Ovalles
- Gastroenterology and Digestive Endoscopy, Hospital Luis E Aybar, Santo Domingo, Dominican Republic
| | - Juan Eloy Paredes-Mendez
- Gastroenterology, Guillermo Almenara National Hospital, Lima, Perú
- Gastroenterology, International Clinic, Lima, Peru
| | | | - David Andrade-Zamora
- Gastroenterology, Hospital of the Ecuadorian Institute of Social Security of Cuenca, Cuenca, Ecuador
| | | | - Cristian Flórez-Sarmiento
- Cellular and Molecular Immunology Group (INMUBO), Universidad El Bosque, Bogotá, Colombia
- Gastroenterology, Hospital Internacional de Colombia, Bucaramanga, Colombia
| | - Guillermo Veitia
- Gastroenterology, Hospital Vargas de Caracas, Caracas, Venezuela
- Gastroenterology, Universidad Central de Venezuela, Caracas, Venezuela
| | - Abel Sánchez
- Gastroenterology and Digestive Endoscopy, Roosevelt Hospital, Guatemala City. Guatemala
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Abdul Malik TF, Beh HC, Selvaraj CS, Mallen CD, Ng CJ, Lee YK. Interventions to promote colorectal cancer screening among people with a family history of colorectal cancer: A scoping review. Prev Med 2024; 189:108137. [PMID: 39277034 DOI: 10.1016/j.ypmed.2024.108137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 09/10/2024] [Accepted: 09/10/2024] [Indexed: 09/17/2024]
Abstract
BACKGROUND The global incidence of colorectal cancer (CRC) is rising, with people having a family history of CRC (PFH-CRC) facing double the risk compared to the average-risk population. Despite this, CRC screening uptake among PFH-CRC remains low. There is a lack of systematic mapping of interventions promoting CRC screening in this high-risk population. OBJECTIVE We conducted a scoping review to identify the types of interventions targeting PFH-CRC, their effectiveness in increasing CRC screening uptake, and the elements associated with the outcomes. METHODS The Joanna Briggs Institute methodology for scoping review was followed. The search for eligible articles was conducted from the inception of each database until 17 July 2024 in PubMed, EMBASE, CINAHL, Cochrane, PsycINFO and Web of Science with no restrictions on language. RESULTS Thirty studies from 1995 to 2023 across 13 countries were included; mostly from high-income countries. There was considerable variability in study design, intervention characteristics, and screening outcomes. Eleven studies used theoretical frameworks in intervention development. Fourteen studies reported statistically significant increases in screening uptake among PFH-CRC, most using complex, multiple-component interventions. Tailored print materials and patient navigation more consistently demonstrated increased screening uptake, while counselling yielded mixed results. CONCLUSION Interventions for promoting CRC screening uptake in PFH-CRC commonly incorporate print material, patient navigation and counselling, often combined into complex interventions. Future research should include more implementation studies to translate these interventions into real-world settings. Additionally, there are gaps in research from low- and middle-income countries, highlighting the need for further research in these resource-limited settings.
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Affiliation(s)
- Tun Firzara Abdul Malik
- Department of Primary Care Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
| | - Hooi Chin Beh
- Department of Primary Care Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
| | - Christine Shamala Selvaraj
- Department of Primary Care Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
| | | | - Chirk Jenn Ng
- Department of Research, SingHealth Polyclinics, Singapore 150167, Singapore; Duke-NUS Medical School, Singapore 169857, Singapore.
| | - Yew Kong Lee
- Department of Primary Care Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia.
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Șerban RE, Boldeanu MV, Florescu DN, Ionescu M, Șerbănescu MS, Boldeanu L, Florescu MM, Stepan MD, Obleagă VC, Constantin C, Popescu DM, Streba CT, Vere CC. Comparison between Substance P and Calcitonin Gene-Related Peptide and Their Receptors in Colorectal Adenocarcinoma. J Clin Med 2024; 13:5616. [PMID: 39337103 PMCID: PMC11432560 DOI: 10.3390/jcm13185616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/19/2024] [Accepted: 09/20/2024] [Indexed: 09/30/2024] Open
Abstract
Background: Colorectal cancer is a major health problem that still causes many deaths worldwide. Neuropeptides, such as substance P and calcitonin gene-related peptide, play the neurotransmitter and neurohormone roles that increase tumor invasiveness and metastasis potential. This study aimed to see whether these neuropeptides and their receptors-neurokinin 1 receptor and calcitonin receptor-like receptor-correlate with the diagnosis stage, tumor differentiation grade, and different patient characteristics in colorectal cancer and also to compare them. Methods: We performed serum analyses of substance P and CGRP levels in patients with colorectal cancer and also the immunohistochemical analysis of their receptors in colorectal tumors and then correlated them with the disease stage and with different tumor characteristics. Results: We demonstrated that both substance P and calcitonin gene-related peptide had increased levels in colorectal cancer and that their levels correlated with the stage of the disease and with the tumor differentiation grade. We also demonstrated the correlation of NK-1R and CRLR higher immunohistochemical scores with advanced and poorly differentiated tumors. Conclusions: This study demonstrates that the neuropeptides SP and CGRP and their receptors NK-1R and CRLR could play a role in the pathogenesis of colorectal cancer, and they could be used as diagnostic and prognostic markers and could represent potential therapeutic targets.
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Affiliation(s)
- Robert-Emmanuel Șerban
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (R.-E.Ș.); (C.C.V.)
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania
| | - Mihail Virgil Boldeanu
- Department of Immunology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan Nicolae Florescu
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (R.-E.Ș.); (C.C.V.)
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania
| | - Mihaela Ionescu
- Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mircea-Sebastian Șerbănescu
- Department of Medical Informatics and Biostatistics, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Lidia Boldeanu
- Department of Microbiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mirela-Marinela Florescu
- Department of Pathology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mioara-Desdemona Stepan
- Department of Infant Care-Pediatrics-Neonatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Vasile-Cosmin Obleagă
- Department of Surgery, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Cristian Constantin
- Department of Radiology and Medical Imaging, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dragoş-Marian Popescu
- Department of Extreme Conditions Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Costin Teodor Streba
- Department of Scientific Research Methodology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
- Department of Pulmonology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Cristin Constantin Vere
- Department of Gastroenterology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (R.-E.Ș.); (C.C.V.)
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania
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9
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Jeon EH, Park SY, Park KU, Lee YH. Ribosomal Protein L9 Maintains Stemness of Colorectal Cancer via an ID-1 Dependent Mechanism. J Cancer Prev 2024; 29:25-31. [PMID: 38957590 PMCID: PMC11215338 DOI: 10.15430/jcp.24.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Revised: 06/12/2024] [Accepted: 06/17/2024] [Indexed: 07/04/2024] Open
Abstract
The identification of therapeutic target genes that are functionally involved in stemness is crucial to effectively cure patients with metastatic carcinoma. We have previously reported that inhibition of ribosomal protein L9 (RPL9) expression suppresses the growth of colorectal cancer (CRC) cells by inactivating the inhibitor of DNA-binding 1 (ID-1) signaling axis, which is functionally associated with cancer cell survival. In addition to cell proliferation, ID-1 is also involved in the maintenance of cancer stemness. Thus, we aimed in this study to investigate whether the function of RPL9 could correlate with CRC stem cell-like properties. Here, we demonstrated that siRNA silencing of RPL9 reduced the invasiveness and migrative capabilities of HT29 and HCT116 parental cell populations and the capacity for sphere formation in the HT29 parental cell population. CD133+ cancer stem cells (CSCs) were then separated from CD133- cancer cells of the HT29 parental cell culture and treated with RPL9-specific siRNAs to verify the effects of RPL9 targeting on stemness. As a result, knockdown of RPL9 significantly suppressed the proliferative potential of CD133+ colorectal CSCs, accompanied by a reduction in CD133, ID-1, and p-IκBα levels. In line with these molecular alterations, targeting RPL9 inhibited the invasion, migration, and sphere-forming capacity of CD133+ HT29 CSCs. Taken together, these findings suggest that RPL9 promotes CRC stemness via ID-1 and that RPL9 could be a potential therapeutic target for both primary CRC treatment and the prevention of metastasis and/or recurrence.
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Affiliation(s)
- Eun-Hye Jeon
- Department of Molecular Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - So-Young Park
- Department of Molecular Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Keon Uk Park
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Yun-Han Lee
- Department of Molecular Medicine, Keimyung University School of Medicine, Daegu, Korea
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10
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O'Connell RM, Hoti E. Challenges and Opportunities for Precision Surgery for Colorectal Liver Metastases. Cancers (Basel) 2024; 16:2379. [PMID: 39001441 PMCID: PMC11240734 DOI: 10.3390/cancers16132379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2024] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
The incidence of colorectal cancer and colorectal liver metastases (CRLM) is increasing globally due to an interaction of environmental and genetic factors. A minority of patients with CRLM have surgically resectable disease, but for those who have resection as part of multimodal therapy for their disease, long-term survival has been shown. Precision surgery-the idea of careful patient selection and targeting of surgical intervention, such that treatments shown to be proven to benefit on a population level are the optimal treatment for each individual patient-is the new paradigm of care. Key to this is the understanding of tumour molecular biology and clinically relevant mutations, such as KRAS, BRAF, and microsatellite instability (MSI), which can predict poorer overall outcomes and a poorer response to systemic therapy. The emergence of immunotherapy and hepatic artery infusion (HAI) pumps show potential to convert previously unresectable disease to resectable disease, in addition to established systemic and locoregional therapies, but the surgeon must be wary of poor-quality livers and the spectre of post-hepatectomy liver failure (PHLF). Volume modulation, a cornerstone of hepatic surgery for a generation, has been given a shot in the arm with the advent of liver venous depletion (LVD) ensuring significantly more hypertrophy of the future liver remnant (FLR). The optimal timing of liver resection for those patients with synchronous disease is yet to be truly established, but evidence would suggest that those patients requiring complex colorectal surgery and major liver resection are best served with a staged approach. In the operating room, parenchyma-preserving minimally invasive surgery (MIS) can dramatically reduce the surgical insult to the patient and lead to better perioperative outcomes, with quicker return to function.
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Affiliation(s)
- Robert Michael O'Connell
- Department of Hepatopancreaticobiliary and Transplantation Surgery, Saint Vincent's University Hospital, D04 T6F4 Dublin, Ireland
| | - Emir Hoti
- Department of Hepatopancreaticobiliary and Transplantation Surgery, Saint Vincent's University Hospital, D04 T6F4 Dublin, Ireland
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11
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Abstract
Colorectal cancer remains the third leading cause of cancer death in the United States. Colorectal cancer screening allows for prevention and early detection of precancerous and cancerous lesions, and screening has been shown to be effective in preventing colorectal cancer deaths. Screening recommendations vary by patient risk profile. A variety of screening modalities exist.
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Affiliation(s)
- Matthew Jacobsson
- Virginia Mason Franciscan Health, St. Joseph Medical Center General Surgery Residency, 1708 South Yakima Avenue Suite 105 & 112, Tacoma, WA 98408, USA
| | - Vitas Wagner
- Virginia Mason Franciscan Health, St. Joseph Medical Center General Surgery Residency, 1708 South Yakima Avenue Suite 105 & 112, Tacoma, WA 98408, USA
| | - Shalini Kanneganti
- Virginia Mason Franciscan Health, Franciscan Surgical Associates at St. Joseph, 1708 South Yakima Avenue Suite 105 & 112, Tacoma, WA 98405, USA.
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12
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Roshandel G, Ghasemi-Kebria F, Malekzadeh R. Colorectal Cancer: Epidemiology, Risk Factors, and Prevention. Cancers (Basel) 2024; 16:1530. [PMID: 38672612 PMCID: PMC11049480 DOI: 10.3390/cancers16081530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 04/09/2024] [Accepted: 04/15/2024] [Indexed: 04/28/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality worldwide. There are disparities in the epidemiology of CRC across different populations, most probably due to differences in exposure to lifestyle and environmental factors related to CRC. Prevention is the most effective method for controlling CRC. Primary prevention includes determining and avoiding modifiable risk factors (e.g., alcohol consumption, smoking, and dietary factors) as well as increasing protective factors (e.g., physical activity, aspirin). Further studies, especially randomized, controlled trials, are needed to clarify the association between CRC incidence and exposure to different risk factors or protective factors. Detection and removal of precancerous colorectal lesions is also an effective strategy for controlling CRC. Multiple factors, both at the individual and community levels (e.g., patient preferences, availability of screening modalities, costs, benefits, and adverse events), should be taken into account in designing and implementing CRC screening programs. Health policymakers should consider the best decision in identifying the starting age and selection of the most effective screening strategies for the target population. This review aims to present updated evidence on the epidemiology, risk factors, and prevention of CRC.
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Affiliation(s)
- Gholamreza Roshandel
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 49178-67439, Iran; (G.R.); (F.G.-K.)
| | - Fatemeh Ghasemi-Kebria
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 49178-67439, Iran; (G.R.); (F.G.-K.)
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 14117-13135, Iran
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13
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Abstract
Colorectal cancer (CRC) is the second leading cause of cancer death. Screening has been proven to reduce both cancer incidence and cancer-related mortality. Various screening tests are available, each with their own advantages and disadvantages and varying levels of evidence to support their use. Clinicians should offer CRC screening to average-risk persons aged 50 to 75 years; starting screening at age 45 years remains controversial. Screening may be beneficial in select persons aged 76 to 85 years, based on their overall health and screening history. Offering a choice of screening tests or sequentially offering an alternate test for those who do not complete screening can significantly increase participation.
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Affiliation(s)
- Swati G Patel
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz School of Medicine, and Division of Gastroenterology and Hepatology, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, Colorado (S.G.P.)
| | - Jason A Dominitz
- Gastroenterology Section, Veterans Affairs Puget Sound Health Care System, and Division of Gastroenterology, University of Washington, Seattle, Washington (J.A.D.)
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14
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Rashid G, Bhat GA, Rather TB, Akhtar K, Parveiz I, Ahmad SN, Rasool MT, Jan FA, Hafez W, Mudassar S. Assessing Colorectal Cancer Susceptibility in Kashmir, India: Insights from Xenobiotic Metabolism Gene Variants and Family Cancer History—A Comprehensive Case–Control Study. Indian J Clin Biochem 2024. [DOI: 10.1007/s12291-024-01196-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 02/05/2024] [Indexed: 10/14/2024]
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15
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Faramarzi S, Kiani B, Faramarzi S, Firouraghi N. Cancer patterns in Iran: a gender-specific spatial modelling of cancer incidence during 2014-2017. BMC Cancer 2024; 24:191. [PMID: 38342916 PMCID: PMC10860283 DOI: 10.1186/s12885-024-11940-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2023] [Accepted: 02/01/2024] [Indexed: 02/13/2024] Open
Abstract
BACKGROUND Cancer is a significant public health concern and the second leading cause of death. This study aims to visualize spatial patterns of top common cancer types and identify high-risk and low-risk counties for these cancers in Iran from 2014 to 2017. METHODS In this study, we analyzed 482,229 newly diagnosed cancer cases recorded by the Iranian National Population-Based Cancer Registry from 2014 to 2017. We employed a purely spatial scanning model and local Moran I analysis to explore spatial patterns across Iran. RESULTS Approximately 53% of all cases were male. The average age of cancer diagnosis was 62.58 ± 17.42 years for males and 56.11 ± 17.33years for females. Stomach cancer was the most common cancer in men. The northern and northwestern regions of Iran were identified as high-risk areas for stomach cancer in both genders, with a relative risk (RR) ranging from 1.26 to 2.64 in males and 1.19 to 3.32 in females. These areas recognized as high-risk areas for trachea, bronchus, and lung (TBL) cancer specifically in males (RR:1.15-2.02). Central regions of Iran were identified as high-risk areas for non-melanoma skin cancers in both genders, ranking as the second most common cancer (RR:1.18-5.93 in males and 1.24-5.38 in females). Furthermore, bladder cancer in males (RR:1.32-2.77) and thyroid cancer in females (RR:1.88-3.10) showed concentration in the central part of Iran. Breast cancer, being the most common cancer among women (RR:1.23-5.54), exhibited concentration in the northern regions of the country. Also, northern regions of Iran were identified as high-risk clusters for colon cancer (RR:1.31-3.31 in males and 1.33-4.13 in females), and prostate cancer in males (RR:1.22-2.31). Brain, nervous system cancer, ranked sixth among women (RR:1.26-5.25) in central areas. CONCLUSIONS The study's revelations on the spatial patterns of common cancer incidence in Iran provide crucial insights into the distribution and trends of these diseases. The identification of high-risk areas equips policymakers with valuable information to tailor targeted screening programs, facilitating early diagnosis and effective disease control strategies.
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Affiliation(s)
- Sharareh Faramarzi
- Department of Medical Informatics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Behzad Kiani
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Shahla Faramarzi
- Department of Health Information Management School of Health Management and Information Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Neda Firouraghi
- Department of Medical Informatics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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16
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Martín-García D, Téllez T, Redondo M, García-Aranda M. The use of SP/Neurokinin-1 as a Therapeutic Target in Colon and Rectal Cancer. Curr Med Chem 2024; 31:6487-6509. [PMID: 37861026 DOI: 10.2174/0109298673261625230924114406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 08/08/2023] [Accepted: 08/18/2023] [Indexed: 10/21/2023]
Abstract
Different studies have highlighted the role of Substance P / Neurokinin 1 Receptor (SP/NK-1R) axis in multiple hallmarks of cancer including cell transformation, proliferation, and migration as well as angiogenesis and metastasis of a wide range of solid tumors including colorectal cancer. Until now, the selective high-affinity antagonist of human SP/NK1-R aprepitant (Emend) has been authorized by the Food and Drug Administration as a low dosage medication to manage and treat chemotherapy-induced nausea. However, increasing evidence in recent years support the potential utility of high doses of aprepitant as an antitumor agent and thus, opening the possibility to the pharmacological repositioning of SP/NK1-R antagonists as an adjuvant therapy to conventional cancer treatments. In this review, we summarize current knowledge on the molecular basis of colorectal cancer as well as the pathophysiological importance of SP/NK1-R and the potential utility of SP/NK-1R axis as a therapeutic target in this malignancy.
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Affiliation(s)
| | - Teresa Téllez
- Surgical Specialties, Biochemistry and Immunology, University of Malaga, Spain
| | - Maximino Redondo
- Surgical Specialties, Biochemistry and Immunology, University of Malaga, Spain
| | - Marilina García-Aranda
- Surgical Specialties, Biochemistry and Immunology, University of Malaga, Spain
- Research and Innovation Unit, Hospital Costa del Sol, 29602 Marbella, Spain
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17
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Van Dingenen L, Segers C, Wouters S, Mysara M, Leys N, Kumar-Singh S, Malhotra-Kumar S, Van Houdt R. Dissecting the role of the gut microbiome and fecal microbiota transplantation in radio- and immunotherapy treatment of colorectal cancer. Front Cell Infect Microbiol 2023; 13:1298264. [PMID: 38035338 PMCID: PMC10687483 DOI: 10.3389/fcimb.2023.1298264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2023] [Accepted: 10/31/2023] [Indexed: 12/02/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and poses a major burden on the human health worldwide. At the moment, treatment of CRC consists of surgery in combination with (neo)adjuvant chemotherapy and/or radiotherapy. More recently, immune checkpoint blockers (ICBs) have also been approved for CRC treatment. In addition, recent studies have shown that radiotherapy and ICBs act synergistically, with radiotherapy stimulating the immune system that is activated by ICBs. However, both treatments are also associated with severe toxicity and efficacy issues, which can lead to temporary or permanent discontinuation of these treatment programs. There's growing evidence pointing to the gut microbiome playing a role in these issues. Some microorganisms seem to contribute to radiotherapy-associated toxicity and hinder ICB efficacy, while others seem to reduce radiotherapy-associated toxicity or enhance ICB efficacy. Consequently, fecal microbiota transplantation (FMT) has been applied to reduce radio- and immunotherapy-related toxicity and enhance their efficacies. Here, we have reviewed the currently available preclinical and clinical data in CRC treatment, with a focus on how the gut microbiome influences radio- and immunotherapy toxicity and efficacy and if these treatments could benefit from FMT.
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Affiliation(s)
- Lena Van Dingenen
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
- Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
| | - Charlotte Segers
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
| | - Shari Wouters
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
- Molecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
| | - Mohamed Mysara
- Bioinformatics Group, Center for Informatics Science, School of Information Technology and Computer Science, Nile University, Giza, Egypt
| | - Natalie Leys
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
| | - Samir Kumar-Singh
- Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
- Molecular Pathology Group, Laboratory of Cell Biology and Histology, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
| | - Surbhi Malhotra-Kumar
- Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute, Faculty of Medicine, University of Antwerp, Antwerp, Belgium
| | - Rob Van Houdt
- Nuclear Medical Applications, Belgian Nuclear Research Centre, SCK CEN, Mol, Belgium
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18
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Issaka RB, Chan AT, Gupta S. AGA Clinical Practice Update on Risk Stratification for Colorectal Cancer Screening and Post-Polypectomy Surveillance: Expert Review. Gastroenterology 2023; 165:1280-1291. [PMID: 37737817 PMCID: PMC10591903 DOI: 10.1053/j.gastro.2023.06.033] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/20/2023] [Accepted: 06/30/2023] [Indexed: 09/23/2023]
Abstract
DESCRIPTION Since the early 2000s, there has been a rapid decline in colorectal cancer (CRC) mortality, due in large part to screening and removal of precancerous polyps. Despite these improvements, CRC remains the second leading cause of cancer deaths in the United States, with approximately 53,000 deaths projected in 2023. The aim of this American Gastroenterological Association (AGA) Clinical Practice Update Expert Review was to describe how individuals should be risk-stratified for CRC screening and post-polypectomy surveillance and to highlight opportunities for future research to fill gaps in the existing literature. METHODS This Expert Review was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPUC and external peer review through standard procedures of Gastroenterology. These Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: All individuals with a first-degree relative (defined as a parent, sibling, or child) who was diagnosed with CRC, particularly before the age of 50 years, should be considered at increased risk for CRC. BEST PRACTICE ADVICE 2: All individuals without a personal history of CRC, inflammatory bowel disease, hereditary CRC syndromes, other CRC predisposing conditions, or a family history of CRC should be considered at average risk for CRC. BEST PRACTICE ADVICE 3: Individuals at average risk for CRC should initiate screening at age 45 years and individuals at increased risk for CRC due to having a first-degree relative with CRC should initiate screening 10 years before the age at diagnosis of the youngest affected relative or age 40 years, whichever is earlier. BEST PRACTICE ADVICE 4: Risk stratification for initiation of CRC screening should be based on an individual's age, a known or suspected predisposing hereditary CRC syndrome, and/or a family history of CRC. BEST PRACTICE ADVICE 5: The decision to continue CRC screening in individuals older than 75 years should be individualized, based on an assessment of risks, benefits, screening history, and comorbidities. BEST PRACTICE ADVICE 6: Screening options for individuals at average risk for CRC should include colonoscopy, fecal immunochemical test, flexible sigmoidoscopy plus fecal immunochemical test, multitarget stool DNA fecal immunochemical test, and computed tomography colonography, based on availability and individual preference. BEST PRACTICE ADVICE 7: Colonoscopy should be the screening strategy used for individuals at increased CRC risk. BEST PRACTICE ADVICE 8: The decision to continue post-polypectomy surveillance for individuals older than 75 years should be individualized, based on an assessment of risks, benefits, and comorbidities. BEST PRACTICE ADVICE 9: Risk-stratification tools for CRC screening and post-polypectomy surveillance that emerge from research should be examined for real-world effectiveness and cost-effectiveness in diverse populations (eg, by race, ethnicity, sex, and other sociodemographic factors associated with disparities in CRC outcomes) before widespread implementation.
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Affiliation(s)
- Rachel B Issaka
- Public Health Sciences and Clinical Research Divisions, Fred Hutchinson Cancer Center, Seattle, Washington; Division of Gastroenterology, University of Washington School of Medicine, Seattle, Washington.
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Samir Gupta
- Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California; Section of Gastroenterology, Jennifer Moreno Department of Medical Affairs Medical Center, San Diego, California
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19
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Barnett MI, Wassie MM, Cock C, Bampton PA, Symonds EL. Low Incidence of Colorectal Advanced Neoplasia During Surveillance in Individuals with a Family History of Colorectal Cancer. Dig Dis Sci 2023; 68:4243-4251. [PMID: 37682374 PMCID: PMC10570165 DOI: 10.1007/s10620-023-08053-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 07/21/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Family history of colorectal cancer (CRC) is used to stratify individuals into risk categories which determine timing of initial screening and ongoing CRC surveillance. Evidence for long-term CRC risk following a normal index colonoscopy in family history populations is limited. AIMS To assess the incidence of advanced neoplasia and associated risk factors in a population undergoing surveillance colonoscopies due to family history of CRC. METHODS Surveillance colonoscopy findings were examined in 425 individuals with a family history of CRC, a normal index colonoscopy and a minimum of 10 years of follow-up colonoscopies. Advanced neoplasia risk was determined for three CRC family history categories (near-average, medium and high-risk), accounting for demographics and time after the first colonoscopy. RESULTS The median follow-up was 13.5 years (IQR 11.5-16.0), with an incidence of advanced neoplasia of 14.35% (61/425). The number of affected relatives and age of CRC diagnosis in the youngest relative did not predict the risk of advanced neoplasia (p > 0.05), with no significant differences in advanced neoplasia incidence between the family history categories (p = 0.16). Patients ≥ 60 years showed a fourfold (HR 4.14, 95% CI 1.33-12.89) higher advanced neoplasia risk during surveillance than those < 40 years at index colonoscopy. With each subsequent negative colonoscopy, the risk of advanced neoplasia at ongoing surveillance was reduced. CONCLUSIONS The incidence of advanced neoplasia was low (14.35%), regardless of the family history risk category, with older age being the main risk for advanced neoplasia. Delaying onset of colonoscopy or lengthening surveillance intervals could be a more efficient use of resources in this population.
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Affiliation(s)
| | - Molla M Wassie
- Cancer Research, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, 5042, Australia
| | - Charles Cock
- Cancer Research, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, 5042, Australia
- Department of Gastroenterology and Hepatology, Flinders Medical Centre, Bedford Park, SA, 5042, Australia
| | - Peter A Bampton
- Cancer Research, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, 5042, Australia
| | - Erin L Symonds
- Cancer Research, Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA, 5042, Australia
- Bowel Health Service, Flinders Medical Centre, Bedford Park, SA, 5042, Australia
- Level 3, Flinders Centre for Innovation in Cancer, Bedford Park, SA, 5042, Australia
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20
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Chen T, Zheng B, Yang P, Zhang Z, Su Y, Chen Y, Luo L, Luo D, Lin Y, Xie R, Zeng L. The Incidence and Prognosis Value of Perineural Invasion in Rectal Carcinoma: From Meta-Analyses and Real-World Clinical Pathological Features. Clin Oncol (R Coll Radiol) 2023; 35:e611-e621. [PMID: 37263883 DOI: 10.1016/j.clon.2023.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 04/13/2023] [Accepted: 05/16/2023] [Indexed: 06/03/2023]
Abstract
AIMS Perineural invasion (PNI) is a special type of metastasis of several cancers and has been reported as being a factor for poor prognosis in colorectal carcinoma. However, investigations of PNI in only rectal cancer and a comprehensive analysis combining meta-analyses with real-world case studies remain lacking. MATERIALS AND METHODS First, articles from 2000 to 2020 concerning the relationship between PNI and rectal cancer prognoses and clinical features were meta-analysed. Subsequently, we carried out a retrospective analysis of 312 rectal cancer cases that underwent radical surgery in the real world. The incidence of PNI and the relationship between PNI and prognosis, as well as clinicopathological factors, were investigated. RESULTS The incidence of PNI was 23.09% and 33.01% in the meta-analysis and clinical cases, respectively. PNI occurred as early as stage I (2.94%). Moreover, neoadjuvant therapy significantly reduced the PNI-positive rate (20.34% versus 26.54%). Both meta-analysis and real-world clinical case studies suggested that PNI-positive patients had poorer prognoses than PNI-negative patients. We established an effective risk model consisting of T stage, differentiation and lymphovascular invasion to predict PNI in rectal cancer. CONCLUSION PNI is a poor prognostic factor for rectal cancer and could occur even in stage I. Additionally, neoadjuvant therapy could sufficiently reduce the PNI-positive rate. T stage, lymphovascular invasion and differentiation grade were independent risk factors for PNI and the risk model that included these factors could predict the probability of PNI.
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Affiliation(s)
- T Chen
- Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - B Zheng
- Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - P Yang
- Department of Pathology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - Z Zhang
- Department of Radiology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - Y Su
- Department of General Surgery, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - Y Chen
- Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - L Luo
- Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - D Luo
- Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - Y Lin
- Department of Pathology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
| | - R Xie
- Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
| | - L Zeng
- Department of Abdominal Oncology, The Cancer Center of the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
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Park SY, Seo D, Jeon EH, Park JY, Jang BC, Kim JI, Im SS, Lee JH, Kim S, Cho CH, Lee YH. RPL27 contributes to colorectal cancer proliferation and stemness via PLK1 signaling. Int J Oncol 2023; 63:93. [PMID: 37387446 PMCID: PMC10552708 DOI: 10.3892/ijo.2023.5541] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 06/07/2023] [Indexed: 07/01/2023] Open
Abstract
Although expression of ribosomal protein L27 (RPL27) is upregulated in clinical colorectal cancer (CRC) tissue, to the best of our knowledge, the oncogenic role of RPL27 has not yet been defined. The present study aimed to investigate whether targeting RPL27 could alter CRC progression and determine whether RPL27 gains an extra‑ribosomal function during CRC development. Human CRC cell lines HCT116 and HT29 were transfected with RPL27‑specific small interfering RNA and proliferation was assessed in vitro and in vivo using proliferation assays, fluorescence‑activated cell sorting (FACS) and a xenograft mouse model. Furthermore, RNA sequencing, bioinformatic analysis and western blotting were conducted to explore the underlying mechanisms responsible for RPL27 silencing‑induced CRC phenotypical changes. Inhibiting RPL27 expression suppressed CRC cell proliferation and cell cycle progression and induced apoptotic cell death. Targeting RPL27 significantly inhibited growth of human CRC xenografts in nude mice. Notably, polo‑like kinase 1 (PLK1), which serves an important role in mitotic cell cycle progression and stemness, was downregulated in both HCT116 and HT29 cells following RPL27 silencing. RPL27 silencing reduced the levels of PLK1 protein and G2/M‑associated regulators such as phosphorylated cell division cycle 25C, CDK1 and cyclin B1. Silencing of RPL27 reduced the migration and invasion abilities and sphere‑forming capacity of the parental CRC cell population. In terms of phenotypical changes in cancer stem cells (CSCs), RPL27 silencing suppressed the sphere‑forming capacity of the isolated CD133+ CSC population, which was accompanied by decreased CD133 and PLK1 levels. Taken together, these findings indicated that RPL27 contributed to the promotion of CRC proliferation and stemness via PLK1 signaling and RPL27 may be a useful target in a next‑generation therapeutic strategy for both primary CRC treatment and metastasis prevention.
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Affiliation(s)
- So-Young Park
- Department of Molecular Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
| | - Daekwan Seo
- Department of Bioinformatics, Psomagen Inc., Rockville, MD 20850, USA
| | - Eun-Hye Jeon
- Department of Molecular Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
| | - Jee Young Park
- Department of Immunology, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
| | - Byeong-Churl Jang
- Department of Molecular Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
| | - Jee In Kim
- Department of Molecular Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
| | - Seung-Soon Im
- Department of Physiology, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
| | - Jae-Ho Lee
- Department of Anatomy, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
| | - Shin Kim
- Department of Immunology, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
| | - Chi Heum Cho
- Department of Obstetrics and Gynecology, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
| | - Yun-Han Lee
- Department of Molecular Medicine, Keimyung University School of Medicine, Daegu 42601, Republic of Korea
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22
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Kastrinos F, Kupfer SS, Gupta S. Colorectal Cancer Risk Assessment and Precision Approaches to Screening: Brave New World or Worlds Apart? Gastroenterology 2023; 164:812-827. [PMID: 36841490 PMCID: PMC10370261 DOI: 10.1053/j.gastro.2023.02.021] [Citation(s) in RCA: 41] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/12/2023] [Accepted: 02/17/2023] [Indexed: 02/27/2023]
Abstract
Current colorectal cancer (CRC) screening recommendations take a "one-size-fits-all" approach using age as the major criterion to initiate screening. Precision screening that incorporates factors beyond age to risk stratify individuals could improve on current approaches and optimally use available resources with benefits for patients, providers, and health care systems. Prediction models could identify high-risk groups who would benefit from more intensive screening, while low-risk groups could be recommended less intensive screening incorporating noninvasive screening modalities. In addition to age, prediction models incorporate well-established risk factors such as genetics (eg, family CRC history, germline, and polygenic risk scores), lifestyle (eg, smoking, alcohol, diet, and physical inactivity), sex, and race and ethnicity among others. Although several risk prediction models have been validated, few have been systematically studied for risk-adapted population CRC screening. In order to envisage clinical implementation of precision screening in the future, it will be critical to develop reliable and accurate prediction models that apply to all individuals in a population; prospectively study risk-adapted CRC screening on the population level; garner acceptance from patients and providers; and assess feasibility, resources, cost, and cost-effectiveness of these new paradigms. This review evaluates the current state of risk prediction modeling and provides a roadmap for future implementation of precision CRC screening.
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Affiliation(s)
- Fay Kastrinos
- Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, New York; Division of Digestive and Liver Diseases, Columbia University Medical Center and Vagelos College of Physicians and Surgeons, New York, New York.
| | - Sonia S Kupfer
- University of Chicago, Section of Gastroenterology, Hepatology and Nutrition, Chicago, Illinois
| | - Samir Gupta
- Division of Gastroenterology, Department of Internal Medicine, University of California, San Diego, La Jolla, California; Veterans Affairs San Diego Healthcare System, San Diego, California
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23
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Use of Selective Serotonin Reuptake Inhibitors Is Associated with a Lower Risk of Colorectal Cancer among People with Family History. Cancers (Basel) 2022; 14:cancers14235905. [PMID: 36497383 PMCID: PMC9741129 DOI: 10.3390/cancers14235905] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 11/27/2022] [Accepted: 11/28/2022] [Indexed: 12/02/2022] Open
Abstract
Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. Preclinical and population-based evidence suggests that selective serotonin reuptake inhibitors (SSRIs) might play a role in preventing CRC. We performed a nationwide cohort study to explore whether the use of SSRIs could reduce CRC risk among individuals with family history. We identified individuals aged 50 and above who had one or more first-degree relatives diagnosed with CRC. A total of 38,617 incident SSRI users were identified and matched with 115,851 non-users, on a ratio of 1:3. The Cox regression model was used to calculate hazard ratios (HRs) and 95% CI confidence intervals (CIs). We found a significant negative association between SSRI use and the risk of CRC (adjusted HR, 0.77; 95% CI, 0.70-0.85). Restricted cubic spline regression showed a non-linear dose-responded relationship between SSRI use and CRC risk. The association was stronger in rectal cancer than colon cancer (adjusted HR, 0.73 vs. 0.79), and more pronounced in advanced-stage CRC than early-stage CRC (adjusted HR, 0.73 vs. 0.80). This population-based cohort study suggests that the use of SSRIs is associated with a reduced risk of CRC among individuals with a family history of CRC.
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Zhang N, Sundquist J, Sundquist K, Ji J. Proguanil and atovaquone use is associated with lower colorectal cancer risk: a nationwide cohort study. BMC Med 2022; 20:439. [PMID: 36357883 PMCID: PMC9650910 DOI: 10.1186/s12916-022-02643-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 10/28/2022] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Individuals with a family history of colorectal cancer (CRC) are at a high risk of developing CRC. Preclinical studies suggest that the anti-malaria drug proguanil and atovaquone might play a role in preventing CRC, but population-based evidence is still lacking. METHODS By accessing a couple of nationwide Swedish registers, we performed a cohort study to explore whether using proguanil and atovaquone might associate with a lower risk of CRC by adopting a new-user study design. Adults who have 1 or more first-degree relatives (parents or siblings) diagnosed with CRC were identified and linked with the Prescribed Drug Register to evaluate their administration history of proguanil and atovaquone. Survival analysis of the time to CRC diagnosis with Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS A total of 16,817 incident proguanil/atovaquone users were identified and matched with 168,170 comparisons, who did not use proguanil/atovaquone, on the ratio of 1:10. We found a significant negative association between proguanil/atovaquone use and risk of CRC (adjusted HR, 0.76; 95% CI, 0.62-0.93). Test for trend showed significant dose- and duration-response correlations (P < 0.001). The association was more pronounced in CRC diagnosed at an advanced stage than at an early stage (adjusted HR, 0.69 vs.0.81). CONCLUSIONS This national-wide population-based cohort study showed that the use of proguanil and atovaquone was associated with a reduced risk of CRC among individuals with a family history of CRC.
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Affiliation(s)
- Naiqi Zhang
- Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Jan Waldenströms gata 35, 205 02, Malmö, Sweden.
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Jan Waldenströms gata 35, 205 02, Malmö, Sweden.,Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA.,Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Matsue, Japan
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Jan Waldenströms gata 35, 205 02, Malmö, Sweden.,Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA.,Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Matsue, Japan
| | - Jianguang Ji
- Center for Primary Health Care Research, Lund University/Region Skåne, Skåne University Hospital, Jan Waldenströms gata 35, 205 02, Malmö, Sweden
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Association between A Family History of Colorectal Cancer and the Risk of Colorectal Cancer: A Nationwide Population-Based Study. J Pers Med 2022; 12:jpm12101566. [PMID: 36294706 PMCID: PMC9605451 DOI: 10.3390/jpm12101566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 09/15/2022] [Accepted: 09/19/2022] [Indexed: 12/09/2022] Open
Abstract
Large-scale Asian studies on this topic are lacking. We evaluated the CRC risk associated with family history in the Korean population. We analyzed the data of participants aged ≥40 years who underwent national cancer screening between 2013 and 2014. During a mean follow-up of 4.7 ± 0.8 years, 0.43% of the 292,467 participants with family history and 0.28% of the 1,169,868 participants without family history developed CRC. Participants with a family history in any FDR, parents only, and siblings only had a higher risk of CRC than those without family history; adjusted hazard ratios (HRs) were 1.53, 1.46, and 1.61, respectively. Participants with a family history comprising both parents and siblings had an even higher risk of CRC than those without a family history (HR, 2.34). The HRs for CRC in the 40−49, 50−59, 60−69, 70−79, and ≥80 age groups with family history were 1.72, 1.74, 1.50, 1.30, and 0.78, respectively (p < 0.001). A family history of CRC in any FDR and both parents and siblings was associated with an approximately 1.5- and 2.3-fold increased risk of CRC. The effect of family history was relatively greater in the younger than the older age group.
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26
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Association Between Family History of Gastric Cancer and the Risk of Gastric Cancer and Adenoma: A Nationwide Population-Based Study. Am J Gastroenterol 2022; 117:1255-1263. [PMID: 35613561 DOI: 10.14309/ajg.0000000000001837] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 04/29/2022] [Indexed: 01/05/2023]
Abstract
INTRODUCTION A family history of gastric cancer (GC) is a well-known risk factor for GC. However, the association between family history of GC and the risk of GC and gastric adenoma according to the affected family members is unclear. METHODS We analyzed the data of participants aged ≥40 years who underwent national GC screening between 2013 and 2014. Participants with and without a family history of GC among first-degree relatives were matched by age and sex in a 1:4 ratio. RESULTS During a median follow-up of 4.9 years, 0.96% and 0.46% of 896,721 participants with a family history of GC and 0.65% and 0.32% of 3,586,884 participants without a family history of GC developed GC and gastric adenoma, respectively. A family history of GC among any first-degree relative was a risk factor for GC (adjusted hazard ratio [HR] 1.48, 95% confidence interval 1.45-1.52) and gastric adenoma (HR 1.44, 95% confidence interval 1.39-1.50). The HRs for GC and gastric adenoma were higher in participants with a family history of GC in parents and siblings (2.26 and 2.19, respectively) than in those with a family history of GC in parents only (1.40 and 1.41, respectively) or siblings only (1.59 and 1.47, respectively). The HRs for GC in participants with vs without a family history of GC were 1.62, 1.55, and 1.42 in the 40-49, 50-59, and ≥60 years' age groups of participants, respectively. Similarly, the HRs for gastric adenoma increased with decreasing age of participants. DISCUSSION A family history of GC was a risk factor for both GC and gastric adenoma. The risk of GC and gastric adenoma of the participants was higher when both parents and siblings had GC.
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27
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Feldman D, Rodgers-Fouche L, Chung DC. Surveillance Outcomes in Patients With a Family History of Colorectal Cancer in Both Parents. GASTRO HEP ADVANCES 2022; 2:16-21. [PMID: 39130150 PMCID: PMC11307949 DOI: 10.1016/j.gastha.2022.07.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/19/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims A family history of colorectal cancer (CRC) in a first-degree relative is a well-established risk factor for CRC. When individuals have 2 parents with CRC, the impact on risk is uncertain, and there are no established guidelines for surveillance. We sought to define the surveillance practices and outcomes in individuals with a family history of CRC in both parents. Methods We identified probands with a family history of CRC in both parents from our Hereditary Gastrointestinal Cancer Database. Charts were retrospectively reviewed for colonoscopy surveillance patterns and incidence of adenomas and CRC. Results Sixty-six patients met the inclusion criteria. Forty-two patients (64%) had genetic testing, and no pathogenic germline mutations were identified. During a mean surveillance period of 144 ± 82.2 months and a mean surveillance interval of 33.4 ± 16.6 months, a total of 3.2 ± 8.9 adenomas were found per patient. These were small (median 6.5 mm), and 96% exhibited only low-grade dysplasia. Six patients (9%) were diagnosed with CRC at a mean age of 61.5 ± 11.3 years, corresponding to an incidence rate of 14 cases/10,000 person-years. Patients with CRC were older at first colonoscopy than those without cancer (59 vs 46 years, P = .03), and half of these cases were diagnosed at this first colonoscopy. Conclusion Among patients with a family history of CRC in both parents, cases of CRC were seen primarily in those who significantly delayed their first colonoscopy. Initiation of colonoscopy at age 40 should be recommended to individuals with CRC in both parents, consistent with recommendations for those with 1 first-degree relative with CRC.
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Affiliation(s)
- Dan Feldman
- Division of Gastroenterology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Linda Rodgers-Fouche
- Center for Cancer Risk Assessment, Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
| | - Daniel C. Chung
- Division of Gastroenterology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
- Center for Cancer Risk Assessment, Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
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28
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Huang HC, Shiu BH, Su SC, Huang CC, Ting WC, Chang LC, Yang SF, Chou YE. The Impact of Matrix Metalloproteinase-11 Polymorphisms on Colorectal Cancer Progression and Clinicopathological Characteristics. Diagnostics (Basel) 2022; 12:diagnostics12071685. [PMID: 35885589 PMCID: PMC9317823 DOI: 10.3390/diagnostics12071685] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2022] [Accepted: 07/08/2022] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide and the most prevalent cancer in Taiwan. The matrix metalloproteinase (MMP)-11 is a proteolytic enzyme of the MMP family which is involved in extracellular matrix degradation and tissue remodeling. In this study, we focused on the associations of MMP-11 single-nucleotide polymorphisms (SNPs) with CRC susceptibility and clinicopathological characteristics. The MMP-11 SNPs rs131451, rs738791, rs2267029, rs738792, and rs28382575 in 479 controls and 479 patients with CRC were analyzed with real-time polymerase chain reaction. We found that the MMP-11 SNP rs738792 “TC + CC” genotype was significantly associated with perineural invasion in colon cancer patients after controlling for clinical parameters [OR (95% CI) = 1.783 (1.074–2.960); p = 0.025]. The MMP-11 rs131451 “TC + CC” genotypic variants were correlated with greater tumor T status [OR (95% CI):1.254 (1.025–1.534); p = 0.028] and perineural invasion [OR (95% CI):1.773 (1.027–3.062); p = 0.040) in male CRC patients. Furthermore, analyses of The Cancer Genome Atlas (TCGA) revealed that MMP-11 levels were upregulated in colorectal carcinoma tissue compared with normal tissues and were correlated with advanced stage, larger tumor sizes, and lymph node metastasis. Moreover, the data from the Genotype-Tissue Expression (GTEx) database exhibited that the MMP-11 rs738792 “CC” and “CT” genotypic variants have higher MMP-11 expression than the “TT” genotype. In conclusion, our results have demonstrated that the MMP-11 SNPs rs738792 and rs131451 may have potential to provide biomarkers to evaluate CRC disease progression, and the MMP-11 rs131451 polymorphism may shed light on sex discrepancy in CRC development and prognosis.
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Affiliation(s)
- Hsien-Cheng Huang
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; (H.-C.H.); (B.-H.S.)
- Department of Emergency Medicine, Kuang Tien General Hospital, Taichung 433, Taiwan
| | - Bei-Hao Shiu
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; (H.-C.H.); (B.-H.S.)
- Department of Surgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan; (C.-C.H.); (W.-C.T.)
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Shih-Chi Su
- Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung 204, Taiwan;
- Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou 333, Taiwan
| | - Chi-Chou Huang
- Department of Surgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan; (C.-C.H.); (W.-C.T.)
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Wen-Chien Ting
- Department of Surgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan; (C.-C.H.); (W.-C.T.)
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
| | - Lun-Ching Chang
- Department of Mathematical Sciences, Florida Atlantic University, Boca Raton, FL 33431, USA;
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; (H.-C.H.); (B.-H.S.)
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- Correspondence: (S.-F.Y.); (Y.-E.C.)
| | - Ying-Erh Chou
- School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan
- Correspondence: (S.-F.Y.); (Y.-E.C.)
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29
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Colorectal cancer-derived exosomes and modulation KRAS signaling. CLINICAL & TRANSLATIONAL ONCOLOGY : OFFICIAL PUBLICATION OF THE FEDERATION OF SPANISH ONCOLOGY SOCIETIES AND OF THE NATIONAL CANCER INSTITUTE OF MEXICO 2022; 24:2074-2080. [PMID: 35789981 DOI: 10.1007/s12094-022-02877-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Accepted: 06/13/2022] [Indexed: 10/17/2022]
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide and one of the main causes of cancer-associated mortality. At the period of diagnosis, metastases to other tissues will be present in around 30% of CRC individuals. Individuals with CRC continue to have a poor prognosis despite advances in medication. There is a growing body of literature that CRC develops as a result of the aggregation of various mutations in tumor oncogenes or suppressor genes and that diagnosing cancer in its initial phases may assist in increasing the overall lifespan of individuals with the illness. On the other hand, tumor cells may discharge exosomes in response to oncogenic mutations. By Inhibiting signaling pathways, including the Kirsten rat sarcoma virus (KRAS) mechanism, which is important in a variety of cell activities, exosomes have been shown to cause colorectal cancer in animal studies. The purpose of this review was to summarize the latest discoveries on the modulation of KRAS signaling by exosomes extracted from colorectal cancer.
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30
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Ukashi O, Pflantzer B, Barash Y, Klang E, Segev S, Yablecovitch D, Kopylov U, Ben-Horin S, Laish I. Risk factors and prediction algorithm for advanced neoplasia on screening colonoscopy for average-risk individuals. Therap Adv Gastroenterol 2022; 15:17562848221101291. [PMID: 35795377 PMCID: PMC9252006 DOI: 10.1177/17562848221101291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Accepted: 04/29/2022] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Screening with colonoscopy for all average-risk population is probably not cost-effective due to the limited sources and over-generalization of the risk, and risk stratification can be used to optimize colorectal cancer screening. OBJECTIVES We aimed to assess risk factors for advanced neoplasia (AN) and a classification tree algorithm to predict the risk. DESIGN This is a retrospective cross-sectional study. METHODS This study was composed of consecutive asymptomatic average-risk individuals undergoing first screening colonoscopy between 2008 and 2019. Detailed characteristics including background diseases, habits, and medications were collected. We used multivariable logistic regression to investigate the associations between clinical variables and the presence of AN and built a classification algorithm to predict AN. RESULTS A total of 3856 patients were included (73.2% male, median age 55). Adenoma and AN detection rate were 15.8% and 3.4%, respectively. On multivariable analysis, predictors of AN [odds ratio (OR), 95% confidence interval (CI)] were age (1.04, 1.01-1.06, p = 0.003), male sex (2.69, 1.56-4.64, p < 0.001), and smoking (1.97, 1.38-2.81, p < 0.001). A classification tree algorithm showed that smoking was the most important risk factor for prediction of AN (4.9% versus 2.4%, p < 0.001), followed by age with a cutoff value of 60 in the smokers (8.4% versus 3.8%, p = 0.001) and 50 in the non-smokers (2.9% versus 0.9%, p = 0.004). CONCLUSION Smoking habits, old age, and male gender are highly associated with an increased risk for AN and should be incorporated in the individualized risk-assessment to adapt a screening program.
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Affiliation(s)
| | - Barak Pflantzer
- Department of Internal Medicine A, Sheba Medical Center, Tel Hashomer, Israel,The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Yiftach Barash
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel,Division of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel,DeepVision Lab, Sheba Medical Center, Tel Hashomer, Israel
| | - Eyal Klang
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel,Division of Diagnostic Imaging, Sheba Medical Center, Tel Hashomer, Israel,DeepVision Lab, Sheba Medical Center, Tel Hashomer, Israel
| | - Shlomo Segev
- Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel,Institute of Medical Screening, Sheba Medical Center, Tel Hashomer, Israel
| | - Doron Yablecovitch
- Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel,Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Uri Kopylov
- Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel,Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Shomron Ben-Horin
- Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel,Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - Ido Laish
- Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel,Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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31
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Li Z, Wang K, Shivappa N, Hébert JR, Chen H, Liu H, Jiang X. Inflammatory potential of diet and colorectal carcinogenesis: a prospective longitudinal cohort. Br J Cancer 2022; 126:1735-1743. [PMID: 35136208 PMCID: PMC9174157 DOI: 10.1038/s41416-022-01731-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 12/31/2021] [Accepted: 01/28/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Acknowledging the role of inflammation in colorectal carcinogenesis, this study aimed to evaluate the associations between diet-associated inflammation, as measured by the energy-adjusted dietary inflammatory index (E-DIITM), and distinct stages of colorectal carcinogenesis. METHODS The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial enrolled participants without a colorectal cancer history, who were asked to complete baseline questionnaires and food frequency questionnaires. To estimate the associations between the E-DII and risks of newly incident colorectal adenoma, recurrent adenoma, and colorectal cancer, multivariable-adjusted Cox proportional hazards regression models were employed. RESULTS Among 101,680 participants, with an average age of 65 years, a total of 1177 incident colorectal adenoma cases, 895 recurrent adenoma cases and 1100 colorectal cancer cases were identified. Higher E-DII scores from food and supplement (HRQ5 vs Q1: 0.86 [0.69-1.06], Ptrend: 0.27) or from food only (HRQ5 vs Q1: 0.82 [0.64-1.05], Ptrend: 0.06) were not associated with higher risks of incident adenoma. However, the elevated risk of recurrent adenoma was found in the highest category of E-DII from food plus supplement (HRQ5 vs Q1: 1.63 [1.28-2.03], Ptrend: < 0.001) when compared with the lowest category. A significant association between colorectal cancer risk and E-DII from food plus supplement (HRQ5 vs Q1: 1.34 [1.09-1.65], Ptrend: 0.009) was found, where this association was only pronounced in distal colorectal cancer. CONCLUSION Higher E-DII scores from diet plus supplement but not from diet only were associated with a higher risk of recurrent adenoma and distal colorectal cancer. The role of nutrient supplements on cancer risk, especially when combined with diet, needs to be elucidated in future studies.
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Affiliation(s)
- Zhuyue Li
- West China School of Nursing/West China Hospital, Sichuan University, Chengdu, China
| | - Kang Wang
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
| | - Nitin Shivappa
- Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
- Department of Nutrition, Connecting Health Innovations LLC, Columbia, SC, USA
| | - James R Hébert
- Cancer Prevention and Control Program and Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
- Department of Nutrition, Connecting Health Innovations LLC, Columbia, SC, USA
| | - Hong Chen
- West China School of Nursing/West China Hospital, Sichuan University, Chengdu, China
| | - Hui Liu
- West China Second Hospital, Sichuan University, Chengdu, China
| | - Xiaolian Jiang
- West China School of Nursing/West China Hospital, Sichuan University, Chengdu, China.
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Ness RM. Updates in Screening Recommendations for Colorectal Cancer. J Natl Compr Canc Netw 2022. [DOI: 10.6004/jnccn.2022.5006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
In the past 2 years, several significant changes have been made to the NCCN Guidelines for Colorectal Cancer (CRC) Screening. The age for initiation of screening average-risk adults has been lowered from age 50 to 45 years—without differentiation by age and race—and from age50 to 45 years for those with second- and third-degree relatives with CRC. For several groups, surveillance intervals have been changed. Patients with 1 or 2 low-risk adenomas at index colonoscopy, on the other hand, can now wait 10 years rather than 5 to 7 years between surveillance examinations. The first surveillance examination following resection of large adenomas or sessile serrated polyps (SSPs) with unfavorable-risk characteristics or that were removed piecemeal should now occur at 6 months. For patients with ≥10 adenomas and SSPs on a single colonoscopy, time to first surveillance was lowered to 1 year.
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Yang KD, Wang Y, Zhang F, Luo BH, Feng DY, Zeng ZJ. CircN4BP2L2 promotes colorectal cancer growth and metastasis through regulation of the miR-340-5p/CXCR4 axis. J Transl Med 2022; 102:38-47. [PMID: 34326457 DOI: 10.1038/s41374-021-00632-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2020] [Revised: 06/17/2021] [Accepted: 06/18/2021] [Indexed: 11/09/2022] Open
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. Dysregulation of circular RNAs (circRNAs) appears to be a critical factor in CRC progression. However, mechanistic studies delineating the role of circRNAs in CRC remain limited. In this study, qRT-PCR and western blot assays were used to measure the expression of genes and proteins. Migration, invasion, proliferation, and apoptosis were examined by wound-healing, transwell, CCK-8, colony formation, and flow cytometry assays, respectively. Molecular interactions were validated by a dual-luciferase report system. A xenograft animal model was established to examine in vivo tumor growth and lung metastasis. Our data indicated that circN4BP2L2 expression was increased in CRC tissues and cell lines. Notably, inhibition of circN4BP2L2 effectively inhibited proliferation, migration, and invasion of LoVo cells, and inhibited tumor growth and metastasis in vivo, whereas the forced expression of circN4BP2L2 facilitated the proliferation, migration, and invasion of HT-29 cells. Mechanistic studies revealed that circN4BP2L2 acted as a molecular sponge of miR-340-5p to competitively promote CXCR4 expression. Furthermore, inhibition of miR-340-5p reversed the anti-cancer effects of circN4BP2L2 or CXCR4 silencing. Our data indicated an oncogenic role of circN4BP2L2 in CRC via regulation of the miR-340-5p/CXCR4 axis, which may be a promising biomarker and target for CRC treatment.
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Affiliation(s)
- Ke-Da Yang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China
| | - Ying Wang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China
| | - Fan Zhang
- Department of Gynecology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China
| | - Bai-Hua Luo
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China
| | - De-Yun Feng
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China
| | - Zhi-Jun Zeng
- Department of Geriatric Surgery, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China.
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Fang L, Yang Z, Zhang M, Meng M, Feng J, Chen C. Clinical characteristics and survival analysis of colorectal cancer in China: a retrospective cohort study with 13,328 patients from southern China. Gastroenterol Rep (Oxf) 2021; 9:571-582. [PMID: 34925854 PMCID: PMC8677537 DOI: 10.1093/gastro/goab048] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Revised: 09/30/2021] [Accepted: 10/01/2021] [Indexed: 02/07/2023] Open
Abstract
Background Colorectal cancer (CRC) is one of the most common cancers in China. However, detailed clinical characteristics and survival information are limited. This study aimed to investigate the potential epidemiological and clinical risk factors affecting the survival of CRC patients in southern China. Methods Patients with primary CRC between 1994 and 2019 at the First and the Sixth Affiliated Hospitals of Sun Yat-sen University (Guangzhou, China) were included. Clinical characteristics and survival outcomes were collected from medical records. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS), and Cox's proportional-hazards regression model was used to estimate hazard ratios and 95% confidence intervals. Results Of all 13,328 patients, 60.1% were men; the mean age was 61.3 years; 53.5% had colon cancer. Among all patients, 1,864 (14.0%) were diagnosed with stage IV disease. The 3- and 5-year OS rates were 79.90% and 71.50%, respectively, whereas the 3- and 5-year PFS rates were 70.30% and 63.90%, respectively. The median OS and PFS times were 189 and 149 months, respectively. Among 13,328 patients, 428 (14.0%) patients with poor/undifferentiated cancer suffered recurrence. In patients with stage III and stage IV diseases, the median PFS times of the patients who received chemotherapy were significantly longer than those in patients who had not received chemotherapy (stage III: 147 vs 62 months, P < 0.001; stage IV: 14 vs 9.5 months, P < 0.001). Conclusions This retrospective cohort study illustrates the current status of the clinical characteristics of patients with CRC in southern China. Sex, age, family history, location of cancer occurrence, differentiation status, T status, N status, M status, clinical stage, operation, and surgical margin are independent factors associated with the OS of CRC patients.
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Affiliation(s)
- Lekun Fang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Department of Colorectal Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Ziqing Yang
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Mingliang Zhang
- Department of Colorectal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Manqi Meng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Junyan Feng
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.,Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
| | - Chuangqi Chen
- Department of Colorectal Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P. R. China
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Ghajari H, Sadeghi A, Khodakarim S, Zali M, Nazari SSH. Designing a Predictive Model for Colorectal Neoplasia Diagnosis Based on Clinical and Laboratory Findings in Colonoscopy Candidate Patients. J Gastrointest Cancer 2021; 53:880-887. [PMID: 34851503 DOI: 10.1007/s12029-021-00737-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/17/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Health authorities have expanded two strategies to diminish CRC-related influence: CR screening and improve diagnostic process in symptomatic patients. The aim of the current study is to design a predictive model to identify the most important risk factors that can efficiently predict patients who have high risk of colorectal neoplasia. METHOD A cross-sectional study was constructed to include all patients who had positive test for FIT or had one or more risk factors for colorectal cancer based on the guidelines of detecting high-risk groups for colorectal cancer in Iran. Multivariable binary logistic regression model was constructed for prediction of colorectal neoplasia. We used sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio to check the accuracy. The Hosmer-Lemeshow test, chi-square test, and p value were used to determine the precision of model. RESULT Following an AIC stepwise selection model, only nine potential variables, namely gender, watery diarrhea, IBD, abdominal pain, melena, body mass index, depression drug, anti-inflammatory drug, and age, were found to be a predictor of colorectal neoplasia. The best cut-point probability in the final model was 0.27 and results of sensitivity and specificity, based on maximizing these two criteria, were 66% and 62%, respectively. CONCLUSION Overall, our model prediction was comparable with other risk prediction models for colorectal cancer. It had a modest discriminatory power to distinguish an individual's neoplasia colorectal risk.
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Affiliation(s)
- H Ghajari
- Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - A Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - S Khodakarim
- Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - M Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - S S Hashemi Nazari
- Safety Promotion and Injury Prevention Research Center, Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Chamran Highway, Daneshjoo Blvd, 198353-5511, Velenjak Tehran, PC, Iran
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Huang J, Yu S, Ding L, Ma L, Chen H, Zhou H, Zou Y, Yu M, Lin J, Cui Q. The Dual Role of Circular RNAs as miRNA Sponges in Breast Cancer and Colon Cancer. Biomedicines 2021; 9:biomedicines9111590. [PMID: 34829818 PMCID: PMC8615412 DOI: 10.3390/biomedicines9111590] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2021] [Revised: 10/13/2021] [Accepted: 10/27/2021] [Indexed: 02/07/2023] Open
Abstract
Breast cancer (BC) and colon cancer (CRC) are the two most deadly cancers in the world. These cancers partly share the same genetic background and are partially regulated by the same genes. The outcomes of traditional chemoradiotherapy and surgery remain suboptimal, with high postoperative recurrence and a low survival rate. It is, therefore, urgent to innovate and improve the existing treatment measures. Many studies primarily reported that the microRNA (miRNA) sponge functions of circular RNA (circRNA) in BC and CRC have an indirect relationship between the circRNA–miRNA axis and malignant behaviors. With a covalent ring structure, circRNAs can regulate the expression of target genes in multiple ways, especially by acting as miRNA sponges. Therefore, this review mainly focuses on the roles of circRNAs as miRNA sponges in BC and CRC based on studies over the last three years, thus providing a theoretical reference for finding new therapeutic targets in the future.
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Affiliation(s)
- Jiashu Huang
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
| | - Shenghao Yu
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
| | - Lei Ding
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
| | - Lingyuan Ma
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
| | - Hongjian Chen
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
| | - Hui Zhou
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
| | - Yayan Zou
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
| | - Min Yu
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
| | - Jie Lin
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
| | - Qinghua Cui
- Lab of Biochemistry & Molecular Biology, School of Life Sciences, Yunnan University, Kunming 650091, China; (J.H.); (S.Y.); (L.D.); (L.M.); (H.C.); (H.Z.); (Y.Z.); (M.Y.); (J.L.)
- Key Lab of Molecular Cancer Biology, Yunnan Education Department, Kunming 650091, China
- Correspondence: ; Tel.: +86-871-65031412
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Abstract
Over the past decade, 3D culture models of human and animal cells have found their way into tissue differentiation, drug development, personalized medicine and tumour behaviour studies. Embryoid bodies (EBs) are in vitro 3D cultures established from murine pluripotential stem cells, whereas tumoroids are patient-derived in vitro 3D cultures. This thesis aims to describe a new implication of an embryoid body model and to characterize the patient-specific microenvironment of the parental tumour in relation to tumoroid growth rate. In this thesis, we described a high-throughput monitoring method, where EBs are used as a dynamic angiogenesis model. In this model, digital image analysis (DIA) is implemented on immunohistochemistry (IHC) stained sections of the cultures over time. Furthermore, we have investigated the correlation between the genetic profile and inflammatory microenvironment of parental tumours on the in vitro growth rate of tumoroids. The EBs were cultured in spinner flasks. The samples were collected at days 4, 6, 9, 14, 18 and 21, dehydrated and embedded in paraffin. The histological sections were IHC stained for the endothelial marker CD31 and digitally scanned. The virtual whole-image slides were digitally analysed by Visiopharm® software. Histological evaluation showed vascular-like structures over time. The quantitative DIA was plausible to monitor significant increase in the total area of the EBs and an increase in endothelial differentiation. The tumoroids were established from 32 colorectal adenocarcinomas. The in vitro growth rate of the tumoroids was followed by automated microscopy over an 11-day period. The parental tumours were analysed by next-generation sequencing for KRAS, TP53, PIK3CA, SMAD4, MAP2K1, BRAF, FGFR3 and FBXW7 status. The tumoroids established from KRAS-mutated parental tumours showed a significantly higher growth rate compared to their wild-type counterparts. The density of CD3+ T lymphocytes and CD68+ macrophages was calculated in the centre of the tumours and at the invasive margin of the tumours. The high density of CD3+ cells and the low density of CD68+ cells showed a significant correlation with a higher growth rate of the tumoroids. In conclusion, a novel approach for histological monitoring of endothelial differentiation is presented in the stem cell-derived EBs. Furthermore, the KRAS status and density of CD3+ T cells and macrophages in the parental tumour influence the growth rate of the tumoroids. Our results indicate that these parameters should be included when tumoroids are to be implemented in personalized medicine.
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Affiliation(s)
- Nabi Mousavi
- Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
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Michel M, Kaps L, Maderer A, Galle PR, Moehler M. The Role of p53 Dysfunction in Colorectal Cancer and Its Implication for Therapy. Cancers (Basel) 2021; 13:2296. [PMID: 34064974 PMCID: PMC8150459 DOI: 10.3390/cancers13102296] [Citation(s) in RCA: 65] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/28/2021] [Accepted: 05/03/2021] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. The carcinogenesis of CRC is based on a stepwise accumulation of mutations, leading either to an activation of oncogenes or a deactivation of suppressor genes. The loss of genetic stability triggers activation of proto-oncogenes (e.g., KRAS) and inactivation of tumor suppression genes, namely TP53 and APC, which together drive the transition from adenoma to adenocarcinoma. On the one hand, p53 mutations confer resistance to classical chemotherapy but, on the other hand, they open the door for immunotherapy, as p53-mutated tumors are rich in neoantigens. Aberrant function of the TP53 gene product, p53, also affects stromal and non-stromal cells in the tumor microenvironment. Cancer-associated fibroblasts together with other immunosuppressive cells become valuable assets for the tumor by p53-mediated tumor signaling. In this review, we address the manifold implications of p53 mutations in CRC regarding therapy, treatment response and personalized medicine.
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Affiliation(s)
- Maurice Michel
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
| | - Leonard Kaps
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
- Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center Mainz, 55131 Mainz, Germany
| | - Annett Maderer
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
| | - Peter R. Galle
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
| | - Markus Moehler
- I. Department of Medicine, University Medical Center Mainz, 55131 Mainz, Germany; (M.M.); (L.K.); (A.M.); (P.R.G.)
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Whelton SP, Berning P, Blumenthal RS, Marshall CH, Martin SS, Mortensen MB, Blaha MJ, Dzaye O. Multidisciplinary prevention and management strategies for colorectal cancer and cardiovascular disease. Eur J Intern Med 2021; 87:3-12. [PMID: 33610416 DOI: 10.1016/j.ejim.2021.02.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 01/09/2021] [Accepted: 02/06/2021] [Indexed: 02/06/2023]
Abstract
Colorectal cancer (CRC) and cardiovascular disease (CVD) are leading causes of morbidity and mortality worldwide. Their numerous shared and modifiable risk factors underscore the importance of effective prevention strategies for these largely preventable diseases. Conventionally regarded as separate disease entities, clear pathophysiological links and overlapping risk factors represent an opportunity for synergistic collaborative efforts of oncologists and cardiologists. In addition, current CRC treatment approaches can exert cardiotoxicity and thus increase CVD risk. Given the complex interplay of both diseases and increasing numbers of CRC survivors who are at increased risk for CVD, multidisciplinary cardio-oncological approaches are warranted for optimal patient care from primary prevention to acute disease treatment and long-term surveillance.
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Affiliation(s)
- Seamus P Whelton
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Philipp Berning
- Department of Hematology and Oncology, University Hospital Muenster, Muenster, Germany
| | - Roger S Blumenthal
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Catherine Handy Marshall
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Seth S Martin
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Martin Bødtker Mortensen
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
| | - Michael J Blaha
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Omar Dzaye
- Johns Hopkins Ciccarone Center for Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
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40
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ACG Clinical Guidelines: Colorectal Cancer Screening 2021. Am J Gastroenterol 2021; 116:458-479. [PMID: 33657038 DOI: 10.14309/ajg.0000000000001122] [Citation(s) in RCA: 427] [Impact Index Per Article: 106.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Accepted: 12/02/2020] [Indexed: 12/11/2022]
Abstract
Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. CRC screening efforts are directed toward removal of adenomas and sessile serrated lesions and detection of early-stage CRC. The purpose of this article is to update the 2009 American College of Gastroenterology CRC screening guidelines. The guideline is framed around several key questions. We conducted a comprehensive literature search to include studies through October 2020. The inclusion criteria were studies of any design with men and women age 40 years and older. Detailed recommendations for CRC screening in average-risk individuals and those with a family history of CRC are discussed. We also provide recommendations on the role of aspirin for chemoprevention, quality indicators for colonoscopy, approaches to organized CRC screening and improving adherence to CRC screening. CRC screening must be optimized to allow effective and sustained reduction of CRC incidence and mortality. This can be accomplished by achieving high rates of adherence, quality monitoring and improvement, following evidence-based guidelines, and removing barriers through the spectrum of care from noninvasive screening tests to screening and diagnostic colonoscopy. The development of cost-effective, highly accurate, noninvasive modalities associated with improved overall adherence to the screening process is also a desirable goal.
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Huang W, Li H, Shi X, Lin M, Liao C, Zhang S, Shi W, Zhang L, Zhang X, Gan J. Characterization of genomic alterations in Chinese colorectal cancer patients. Jpn J Clin Oncol 2021; 51:120-129. [PMID: 33106877 DOI: 10.1093/jjco/hyaa182] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2020] [Accepted: 09/08/2020] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE Colorectal cancer is one of the most prevalent types of cancer worldwide. Right-sided and left-sided colorectal cancer (RCC and LCC) patients respond differently to treatment. We aimed to identify the different mutational profile between RCC and LCC and provided evidence for future precision therapy. METHODS A total of 630 Chinese colorectal cancer patients, including 467 (74.1%) LCC and 163 (25.9%) RCC, were enrolled in this cohort. Both formalin-fixed paraffin-embedded tumor tissues and matching blood samples were collected and deep sequenced targeting 450 cancer genes for genomic alteration analysis. Tumor mutational burden was measured by an algorithm developed in-house. Correlation analysis was performed by Fisher's exact test. RESULTS The most common mutated genes were TP53 (77.0%), APC (71.7%), KRAS (50.0%), SMAD4 (19.8%), PIK3CA (18.3%), FBXW7 (17.5%), TCF7L2 (12.5%), SOX9 (11.3%), LRP1B (10.8%), ARID1A (10.3%) and FAT4 (10.3%). The mutation frequencies of TP53 and APC in LCC were significantly higher than that of RCC, while the mutation frequency of PIK3CA was lower than that of RCC. Six gene fusions were specifically detected in RCC patients. Colorectal cancer sites were associated with gender (P = 4.15 × 10-5) and tumor differentiation (P = 0.059). In LCC, the gender-associated genes were FAT4, EP300, FAT1, LRP1, ARID1B, AR, FYN and TAF1, while in RCC, they were ARID1A, SMARCA4, LRP1 and GRIN2A. The mutations of 18 genes were associated with tumor differentiation (8 for LCC and 10 for RCC). High tumor mutational burden was more common in RCC. Our results implied more potential targeted drug therapy opportunities for RCC. CONCLUSION We describe the different molecular characteristics of LCC and RCC. Our result supported a better prognosis of RCC than LCC in Chinese colorectal cancer patients.
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Affiliation(s)
- Wei Huang
- Department of Colorectal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Hui Li
- Department of Colorectal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | | | - Minglin Lin
- Department of Colorectal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Cun Liao
- Department of Colorectal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | | | | | - Lin Zhang
- Origimed Co. Ltd, Shanghai, P. R. China
| | - Xiaolong Zhang
- Department of Colorectal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
| | - Jialiang Gan
- Department of Colorectal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P. R. China
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Engin O, Kilinc G, Salimoglu S. Trends, Risk Factors, and Preventions in Colorectal Cancer. COLON POLYPS AND COLORECTAL CANCER 2021:213-233. [DOI: 10.1007/978-3-030-57273-0_10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Lin CC, Liao TT, Yang MH. Immune Adaptation of Colorectal Cancer Stem Cells and Their Interaction With the Tumor Microenvironment. Front Oncol 2020; 10:588542. [PMID: 33312953 PMCID: PMC7708331 DOI: 10.3389/fonc.2020.588542] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 10/21/2020] [Indexed: 12/13/2022] Open
Abstract
Metastasis is the primary cause of death in colorectal cancer (CRC) patients. Emerging evidence has shown that CRC stem cells (CRCSCs) play a significant role in metastatic dissemination and tumor recurrence. However, strategies for targeting CRCSCs are limited because CRCSCs are resistant to therapeutic interventions and because the tumor microenvironment (TME) provides a supportive niche. Moreover, growing evidence highlights the critical role of CRCSCs in immune adaptation and modulation of the TME. CRCSCs escape immune surveillance by avoiding recognition by the innate immune system and shaping the TME through exosomes, cytokines, and chemokines to generate an immunosuppressive niche that facilitates cancer progression. In this review, we summarize studies investigating the immunomodulatory properties of CRCSCs and their underlying mechanisms in order to improve the efficacy of treatment strategies against advanced CRC.
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Affiliation(s)
- Chun-Chi Lin
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Colorectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Tsai-Tsen Liao
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
| | - Muh-Hwa Yang
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.,Cancer Progression Research Center, National Yang-Ming University, Taipei, Taiwan.,Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
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44
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Wang J, Li R, Li M, Wang C. Fibronectin and colorectal cancer: signaling pathways and clinical implications. J Recept Signal Transduct Res 2020; 41:313-320. [PMID: 32900261 DOI: 10.1080/10799893.2020.1817074] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Colorectal cancer (CRC) is the fourth leading cause of cancer deaths worldwide, with poor prognosis mainly related to metastasis. Fibronectin (FN), a vital component of the extracellular matrix (ECM), has been found involved in tumorigenesis and malignant progression in different types of malignancy. Numerous studies have indicated the distinct expression of FN in various cancers and demonstrated the different functions of FN in the proliferation, migration, and invasion of cancers. Meanwhile, FN isoforms have been extensively used for targeted drug delivery and imaging for tumors. Although a growing number of studies on FN in CRC have been reported, integrated reviews on the relationship between FN and CRC are rare. In this review, we will summarize the association between FN and CRC, including the signaling pathways and molecules involved in, as well as potential diagnostic and therapeutic values of FN for patients with CRC.
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Affiliation(s)
- Jianan Wang
- Department of Laboratory Medicine, the First Medical Centre, Chinese PLA General Hospital, Beijing, P. R. China
| | - Ruibing Li
- Department of Laboratory Medicine, the First Medical Centre, Chinese PLA General Hospital, Beijing, P. R. China
| | - Mianyang Li
- Department of Laboratory Medicine, the First Medical Centre, Chinese PLA General Hospital, Beijing, P. R. China
| | - Chengbin Wang
- Department of Laboratory Medicine, the First Medical Centre, Chinese PLA General Hospital, Beijing, P. R. China
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Knapp GC, Alatise OI, Olasehinde OO, Adeyeye A, Ayandipo OO, Weiser MR, Kingham TP. Is Colorectal Cancer Screening Appropriate in Nigeria? J Glob Oncol 2020; 5:1-10. [PMID: 31170018 PMCID: PMC6613663 DOI: 10.1200/jgo.19.00035] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE The global burden of colorectal cancer (CRC) will continue to increase for the foreseeable future, largely driven by increasing incidence and mortality in low- and middle-income countries (LMICs) such as Nigeria. METHODS We used the Wilson-Jungner framework (1968) to review the literature relevant to CRC screening in Nigeria and propose areas for future research and investment. RESULTS Screening is effective when the condition sought is both important and treatable within the system under evaluation. The incidence of CRC is likely increasing, although the exact burden of disease in Nigeria remains poorly understood and access to definitive diagnosis and treatment has not been systematically quantified. In high-income countries (HICs), CRC screening builds on a well-known natural history. In Nigeria, a higher proportion of CRC seems to demonstrate microsatellite instability, which is dissimilar to the molecular profile in HICs. Prospective trials, tissue banking, and next-generation sequencing should be leveraged to better understand these potential differences and the implications for screening. Fecal immunochemical test for hemoglobin (FIT) is recommended for LMICs that are considering CRC screening. However, FIT has not been validated in Nigeria, and questions about the impact of high ambient temperature, endemic parasitic infection, and feasibility remain unanswered. Prospective trials are needed to validate the efficacy of stool-based screening, and these trials should consider concomitant ova and parasite testing. CONCLUSION Using the Wilson-Jungner framework, additional work is needed before organized CRC screening will be effective in Nigeria. These deficits can be addressed without missing the window to mitigate the increasing burden of CRC in the medium to long term.
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Saya S, McIntosh JG, Winship IM, Clendenning M, Milton S, Oberoi J, Dowty JG, Buchanan DD, Jenkins MA, Emery JD. A Genomic Test for Colorectal Cancer Risk: Is This Acceptable and Feasible in Primary Care? Public Health Genomics 2020; 23:110-121. [PMID: 32688362 DOI: 10.1159/000508963] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 05/26/2020] [Indexed: 11/19/2022] Open
Abstract
INTRODUCTION Genomic tests can predict risk and tailor screening recommendations for colorectal cancer (CRC). Primary care could be suitable for their widespread implementation. OBJECTIVE We aimed to assess the feasibility and acceptability of administering a CRC genomic test in primary care. METHODS Participants aged 45-74 years recruited from 4 Australian general practices were offered a genomic CRC risk test. Participants received brief verbal information about the test comprising 45 CRC-associated single-nucleotide polymorphisms, before choosing whether to undertake the test. Personalized risks were given to testers. Uptake and knowledge of the genomic test, cancer-specific anxiety (Cancer Worry Scale), psychosocial impact (Multidimensional Impact of Cancer Risk Assessment [MICRA] score), and impact on CRC screening behaviour within 6 months were measured. RESULTS In 150 participants, test uptake was high (126, 84%), with 125 (83%) having good knowledge of the genomic test. Moderate risk participants were impacted more by the test (MICRA mean: 15.9) than average risk participants (mean: 9.5, difference in means: 6.4, 95% confidence interval (CI): 1.5, 11.2, p = 0.01), but all scores were low. Average risk participants' cancer-specific anxiety decreased (mean differences from baseline: 1 month -0.5, 95% CI: -1.0, -0.1, p = 0.03; 6 months -0.6, 95% CI: -1.0, -0.2, p = 0.01). We found limited evidence for genomic testers being more likely to complete the risk-appropriate CRC screening than non-testers (41 vs. 17%, odds ratio = 3.4, 95% CI: 0.6, 34.8, p = 0.19), but some mediators of screening behaviour were altered in genomic testers. CONCLUSIONS Genomic testing for CRC risk in primary care is acceptable and likely feasible. Further development of the risk assessment intervention could strengthen the impact on screening behaviour.
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Affiliation(s)
- Sibel Saya
- Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia, .,Department of General Practice, University of Melbourne, Melbourne, Victoria, Australia,
| | - Jennifer G McIntosh
- Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.,Department of General Practice, University of Melbourne, Melbourne, Victoria, Australia.,Department of Software Systems & Cybersecurity, Monash University, Melbourne, Victoria, Australia
| | - Ingrid M Winship
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.,Genomic Medicine & Family Cancer Clinic, Royal Melbourne Hospital, Melbourne, Victoria, Australia
| | - Mark Clendenning
- Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.,Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Shakira Milton
- Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.,Department of General Practice, University of Melbourne, Melbourne, Victoria, Australia
| | - Jasmeen Oberoi
- Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.,Department of General Practice, University of Melbourne, Melbourne, Victoria, Australia
| | - James G Dowty
- Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria, Australia
| | - Daniel D Buchanan
- Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.,Genomic Medicine & Family Cancer Clinic, Royal Melbourne Hospital, Melbourne, Victoria, Australia.,Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Melbourne, Victoria, Australia
| | - Mark A Jenkins
- Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.,Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria, Australia
| | - Jon D Emery
- Centre for Cancer Research, University of Melbourne, Melbourne, Victoria, Australia.,Department of General Practice, University of Melbourne, Melbourne, Victoria, Australia.,The Primary Care Unit, University of Cambridge, Cambridge, United Kingdom
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Ochs-Balcom HM, Kanth P, Farnham JM, Abdelrahman S, Cannon-Albright LA. Colorectal cancer risk based on extended family history and body mass index. Genet Epidemiol 2020; 44:778-784. [PMID: 32677164 DOI: 10.1002/gepi.22338] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 06/18/2020] [Accepted: 06/21/2020] [Indexed: 12/17/2022]
Abstract
Family history and body mass index (BMI) are well-known risk factors for colorectal cancer (CRC), however, their joint effects are not well described. Using linked data for genealogy, self-reported height and weight from driver's licenses, and the Utah Surveillance, Epidemiology, and End-Results cancer registry, we found that an increasing number of first-degree relatives (FDR) with CRC is associated with higher standardized incidence ratio (SIR) for overweight/obese probands but not for under/normal weight probands. For probands with two CRC-affected FDRs, the SIR = 1.91 (95% CI [0.52, 4.89]) for under/normal weight probands and SIR = 4.31 (95% CI [2.46, 7.00]) for overweight/obese probands. In the absence of CRC-affected FDRs, any number of CRC-affected SDRs did not significantly increase CRC risk for under/normal weight probands, but for overweight/obese probands with at least three CRC-affected SDRs the SIR = 2.68 (95% CI [1.29, 4.93]). In the absence of CRC-affected FDRs and SDRs, any number of CRC-affected third-degree relatives (TDRs) did not increase risk in under/normal weight probands, but significantly elevated risk for overweight/obese probands with at least two CRC-affected TDRs was observed; SIR = 1.32 (95% CI [1.04, 1.65]). For nonsyndromic CRC, maximum midlife BMI affects risk based on family history and should be taken into account for CRC risk communication when possible.
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Affiliation(s)
- Heather M Ochs-Balcom
- Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York.,Huntsman Cancer Institute, Salt Lake City, Utah
| | - Priyanka Kanth
- Huntsman Cancer Institute, Salt Lake City, Utah.,Division of Gastroenterology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah
| | - James M Farnham
- Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah
| | - Samir Abdelrahman
- Department of Biomedical Informatics, University of Utah School of Medicine, Salt Lake City, Utah
| | - Lisa A Cannon-Albright
- Huntsman Cancer Institute, Salt Lake City, Utah.,Division of Genetic Epidemiology, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, Utah.,George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah
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48
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Kolb JM, Ahnen DJ, Samadder NJ. Evidenced-Based Screening Strategies for a Positive Family History. Gastrointest Endosc Clin N Am 2020; 30:597-609. [PMID: 32439091 PMCID: PMC7302941 DOI: 10.1016/j.giec.2020.02.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The most commonly recognized high-risk group for colorectal cancer (CRC) is individuals with a positive family history. It is generally recognized that those with a first-degree relative (FDR) with CRC are at a 2-fold or higher risk of CRC or advanced neoplasia. FDRs of patients with advanced adenomas have a similarly increased risk. Accordingly, all major US guidelines recommend starting CRC screening by age 40 in these groups. Barriers to screening this group include patient lack of knowledge on family and polyp history, provider limitations in collecting family history, and insufficient application of guidelines.
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Affiliation(s)
- Jennifer M. Kolb
- Division of Gastroenterology & Hepatology, University of Colorado Hospital, Anschutz Medical Campus, Aurora, CO, USA;,Corresponding author. Division of Gastroenterology & Hepatology, University of Colorado Hospital, Anschutz Medical Campus, 1635 Aurora Court, F735, Aurora, CO 80045.,
| | - Dennis J. Ahnen
- Division of Gastroenterology & Hepatology, University of Colorado Hospital, Anschutz Medical Campus, Aurora, CO, USA
| | - N. Jewel Samadder
- Division of Gastroenterology & Hepatology, Mayo Clinic, 5881 East Mayo Boulevard, Phoenix, AZ 85054, USA;,Department of Clinical Genomics, Mayo Clinic, Phoenix, AZ, USA
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Tian Y, Kharazmi E, Brenner H, Xu X, Sundquist K, Sundquist J, Fallah M. Calculating the Starting Age for Screening in Relatives of Patients With Colorectal Cancer Based on Data From Large Nationwide Data Sets. Gastroenterology 2020; 159:159-168.e3. [PMID: 32251666 DOI: 10.1053/j.gastro.2020.03.063] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 02/17/2020] [Accepted: 03/24/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Although colorectal cancer (CRC) screening guidelines acknowledge the need for earlier screening for high-risk individuals, such as those with family history of CRC, there is limited information on how many years earlier these high-risk individuals should be screened; current practice is based on weak evidence. We aimed to provide risk-adapted recommendations on the starting age of CRC screening for individuals with different family histories. METHODS We collected data from nationwide family-cancer data sets in Sweden and calculated risk-adapted starting ages of screening for individuals with different family histories of CRC. Family history was defined as a dynamic (time-dependent) variable, allowing for changes during the follow-up period of 1958 through 2015. RESULTS During a follow-up of 12,829,251 individuals with genealogy information, 173,796 developed CRC. The 10-year cumulative risk for the average-risk population at age 50 years (the guideline-recommended age for screening) was 0.44%. Individuals with different family histories of CRC attained this equivalent 0.44% risk 3-29 years earlier than their peers in the general population without such a family history. For example, individuals with 1 affected first-degree relative diagnosed before age 45 years reached the corresponding risk level 16 years earlier. CONCLUSIONS We determined risk-adapted starting ages of CRC screening for close or distant relatives of patients with CRC, using high quality nationwide data sets. These findings might be used in counselling individuals about the appropriate age to start CRC screening, to optimize screening practice, and to supplement guidelines for CRC screening.
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Affiliation(s)
- Yu Tian
- Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Elham Kharazmi
- Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden.
| | - Hermann Brenner
- Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany; German Cancer Consortium, German Cancer Research Center, Heidelberg, Germany
| | - Xing Xu
- Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany
| | - Kristina Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden; Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York; Center for Community-Based Healthcare Research and Education, Department of Functional Pathology, School of Medicine, Shimane University, Japan
| | - Jan Sundquist
- Center for Primary Health Care Research, Lund University, Malmö, Sweden; Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York; Center for Community-Based Healthcare Research and Education, Department of Functional Pathology, School of Medicine, Shimane University, Japan
| | - Mahdi Fallah
- Division of Preventive Oncology, German Cancer Research Center and National Center for Tumor Diseases, Heidelberg, Germany; Center for Primary Health Care Research, Lund University, Malmö, Sweden.
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50
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Sekiguchi M, Kakugawa Y, Nakamura K, Matsumoto M, Tomizawa Y, Murakami Y, Saito Y, Matsuda T. Family history of colorectal cancer and prevalence of advanced colorectal neoplasia in asymptomatic screened populations in different age groups. Gastrointest Endosc 2020; 91:1361-1370. [PMID: 32004550 DOI: 10.1016/j.gie.2020.01.033] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 01/16/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS The clinical significance of a family history (FH) of colorectal cancer (CRC) in first-degree relatives (FDRs) in CRC screening stratified by different age groups of screened individuals is not fully understood. We investigated the relationship between FH and the presence of advanced colorectal neoplasia (ACN) in screened individuals in different age groups. METHODS Data from screened individuals aged 40 to 54 years (n = 2263) and 55 to 69 years (n = 2621) who underwent their first-ever screening colonoscopy were analyzed. The relationship between FH and ACN was examined, and a multivariate logistic regression analysis incorporating other baseline characteristics was performed. RESULTS Among individuals aged 40 to 54 years, the prevalence of ACN was significantly higher in 249 individuals with affected FDRs than in those without (5.6% vs 1.6%; P < .01), with an adjusted odds ratio of 3.7 (95% confidence interval, 1.9-7.0; P < .01); the prevalence was particularly high in those having FDRs with CRC mortality (7.3%). Among individuals aged 55 to 69 years, the prevalence of ACN was not significantly different between 291 individuals with affected FDRs and those without (5.8% vs 5.8%; P = .95); however, individuals with 2 FDRs with CRC and mortality showed a high prevalence of ACN (17.4% and 42.9%, respectively). CONCLUSIONS An FH of CRC in FDRs was associated with a higher prevalence of ACN in younger individuals, with a particularly high impact of FH of CRC mortality. In contrast, the impact of FH was weaker in older individuals except those having 2 FDRs with CRC or mortality.
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Affiliation(s)
- Masau Sekiguchi
- Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan; Division of Screening Technology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan; Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yasuo Kakugawa
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Keiko Nakamura
- Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan; Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Minori Matsumoto
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Yutaka Tomizawa
- Division of Gastroenterology, Harborview Medical Center, University of Washington, Seattle, Washington, USA
| | | | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Takahisa Matsuda
- Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan; Division of Screening Technology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan; Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
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