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Kordahi MC, Stanaway IB, Avril M, Chac D, Blanc MP, Ross B, Diener C, Jain S, McCleary P, Parker A, Friedman V, Huang J, Burke W, Gibbons SM, Willis AD, Darveau RP, Grady WM, Ko CW, DePaolo RW. Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer. Cell Host Microbe 2021; 29:1589-1598.e6. [PMID: 34536346 DOI: 10.1016/j.chom.2021.08.013] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 07/13/2021] [Accepted: 08/24/2021] [Indexed: 01/06/2023]
Abstract
Colorectal cancer is a major health concern worldwide. Growing evidence for the role of the gut microbiota in the initiation of CRC has sparked interest in approaches that target these microorganisms. However, little is known about the composition and role of the microbiota associated with precancerous polyps. Here, we found distinct microbial signatures between patients with and without polyps and between polyp subtypes using sequencing and culturing techniques. We found a correlation between Bacteroides fragilis recovered and the level of inflammatory cytokines in the mucosa adjacent to the polyp. Additional analysis revealed that B. fragilis from patients with polyps are bft-negative, activate NF-κB through Toll-like receptor 4, induce a pro-inflammatory response, and are enriched in genes associated with LPS biosynthesis. This study provides fundamental insight into the microbial microenvironment of the pre-neoplastic polyp by highlighting strain-specific genomic and proteomic differences, as well as more broad compositional differences in the microbiome.
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Affiliation(s)
- Melissa C Kordahi
- Department of Pathology, University of Washington, Seattle, WA 98195, USA; Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA
| | - Ian B Stanaway
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA
| | - Marion Avril
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Denise Chac
- Department of Pathology, University of Washington, Seattle, WA 98195, USA; Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA
| | - Marie-Pierre Blanc
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Benjamin Ross
- Department of Microbiology and Immunology at Dartmouth College, Hanover, NH 03755, USA
| | - Christian Diener
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Institute for Systems Biology, Seattle, WA 98105
| | - Sumita Jain
- Department of Periodontics, School of Dentistry, University of Washington, Seattle, WA 98195, USA
| | - Paul McCleary
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA
| | - Ana Parker
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA
| | - Vincent Friedman
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA
| | - Jennifer Huang
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
| | - Wynn Burke
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
| | - Sean M Gibbons
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA; Institute for Systems Biology, Seattle, WA 98105
| | - Amy D Willis
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Department of Biostatistics University of Washington, Seattle, WA 98195, USA
| | - Richard P Darveau
- Department of Periodontics, School of Dentistry, University of Washington, Seattle, WA 98195, USA
| | - William M Grady
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
| | - Cynthia W Ko
- Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA
| | - R William DePaolo
- Department of Pathology, University of Washington, Seattle, WA 98195, USA; Center for Microbiome Science & Therapeutics, University of Washington, Seattle, WA 98195, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
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Singh MP, Rai S, Suyal S, Singh SK, Singh NK, Agarwal A, Srivastava S. Genetic and epigenetic markers in colorectal cancer screening: recent advances. Expert Rev Mol Diagn 2017; 17:665-685. [PMID: 28562109 DOI: 10.1080/14737159.2017.1337511] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Colorectal cancer (CRC) is a heterogenous disease which develops from benign intraepithelial lesions known as adenomas to malignant carcinomas. Acquired alterations in Wnt signaling, TGFβ, MAPK pathway genes and clonal propagation of altered cells are responsible for this transformation. Detection of adenomas or early stage cancer in asymptomatic patients and better prognostic and predictive markers is important for improving the clinical management of CRC. Area covered: In this review, the authors have evaluated the potential of genetic and epigenetic alterations as markers for early detection, prognosis and therapeutic predictive potential in the context of CRC. We have discussed molecular heterogeneity present in CRC and its correlation to prognosis and response to therapy. Expert commentary: Molecular marker based CRC screening methods still fail to gain trust of clinicians. Invasive screening methods, molecular heterogeneity, chemoresistance and low quality test samples are some key challenges which need to be addressed in the present context. New sequencing technologies and integrated omics data analysis of individual or population cohort results in GWAS. MPE studies following a GWAS could be future line of research to establish accurate correlations between CRC and its risk factors. This strategy would identify most reliable biomarkers for CRC screening and management.
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Affiliation(s)
- Manish Pratap Singh
- a Department of Biotechnology , Motilal Nehru National Institute of Technology (MNNIT) Allahabad , India
| | - Sandhya Rai
- a Department of Biotechnology , Motilal Nehru National Institute of Technology (MNNIT) Allahabad , India
| | - Shradha Suyal
- a Department of Biotechnology , Motilal Nehru National Institute of Technology (MNNIT) Allahabad , India
| | - Sunil Kumar Singh
- a Department of Biotechnology , Motilal Nehru National Institute of Technology (MNNIT) Allahabad , India
| | - Nand Kumar Singh
- a Department of Biotechnology , Motilal Nehru National Institute of Technology (MNNIT) Allahabad , India
| | - Akash Agarwal
- b Department of Surgical Oncology , Dr. Ram Manohar Lohia Institute of Medical Sciences (DRMLIMS) , Lucknow , India
| | - Sameer Srivastava
- a Department of Biotechnology , Motilal Nehru National Institute of Technology (MNNIT) Allahabad , India
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Annaházi A, Ábrahám S, Farkas K, Rosztóczy A, Inczefi O, Földesi I, Szűcs M, Rutka M, Theodorou V, Eutamene H, Bueno L, Lázár G, Wittmann T, Molnár T, Róka R. A pilot study on faecal MMP-9: a new noninvasive diagnostic marker of colorectal cancer. Br J Cancer 2016; 114:787-792. [PMID: 26908323 PMCID: PMC4984857 DOI: 10.1038/bjc.2016.31] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 01/06/2016] [Accepted: 01/20/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is one of the leading malignancies worldwide, therefore cheap noninvasive screening methods are of great importance. Matrix-metalloproteinase-9 (MMP-9) has a role in the progression of CRC, and its level is elevated in tumour biopsies. Faecal MMP-9 levels are increased in active ulcerative colitis patients, but in CRC patients, they have never been measured. We aimed to assess the faecal MMP-9 levels in patients undergoing total colonoscopy according to endoscopic and histological diagnosis. METHODS One hundred and nine patients provided faecal samples for MMP-9 analysis. A total colonoscopy was performed; suspicious lesions were evaluated by histology. Faecal MMP-9 levels were measured by ELISA. RESULTS The number of patients allocated to different groups were: negative/diverticulosis: 34 (referred to as controls); hyperplastic polyps: 15; adenomas: 32 (22 at high risk); and CRC: 28. Faecal MMP-9 was significantly increased in CRC compared with all other groups (P<0.001). Faecal MMP-9 was suitable to distinguish CRC patients from controls (sensitivity: 89.3%; specificity: 91.2%). By means of a lower cutoff level, faecal MMP-9 identified high-risk adenomas besides CRC (sensitivity: 76%; specificity: 85.3%). This lower cutoff level screened 59% of high-risk adenomas. CONCLUSIONS Faecal MMP-9 may be a promising new noninvasive marker in CRC.
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Affiliation(s)
- Anita Annaházi
- First Department of Medicine, University of Szeged, Korányi Fasor 8-10, Szeged 6720, Hungary
| | - Szabolcs Ábrahám
- Department of Surgery, University of Szeged, Pf. 427, Szeged 6701, Hungary
| | - Klaudia Farkas
- First Department of Medicine, University of Szeged, Korányi Fasor 8-10, Szeged 6720, Hungary
| | - András Rosztóczy
- First Department of Medicine, University of Szeged, Korányi Fasor 8-10, Szeged 6720, Hungary
| | - Orsolya Inczefi
- First Department of Medicine, University of Szeged, Korányi Fasor 8-10, Szeged 6720, Hungary
| | - Imre Földesi
- First Department of Medicine, University of Szeged, Korányi Fasor 8-10, Szeged 6720, Hungary
| | - Mónika Szűcs
- Department of Medical Physics and Informatics, University of Szeged, Korányi Fasor 9, Szeged 6720, Hungary
| | - Mariann Rutka
- First Department of Medicine, University of Szeged, Korányi Fasor 8-10, Szeged 6720, Hungary
| | - Vassilia Theodorou
- Toxalim UMR 1331 INRA/INP/UPS, Neuro-Gastroenterology and Nutrition Unit, 180, Chemin de Tournefeuille, BP.93173, Toulouse Cedex 3, 31027, France
| | - Helene Eutamene
- Toxalim UMR 1331 INRA/INP/UPS, Neuro-Gastroenterology and Nutrition Unit, 180, Chemin de Tournefeuille, BP.93173, Toulouse Cedex 3, 31027, France
| | - Lionel Bueno
- Toxalim UMR 1331 INRA/INP/UPS, Neuro-Gastroenterology and Nutrition Unit, 180, Chemin de Tournefeuille, BP.93173, Toulouse Cedex 3, 31027, France
| | - György Lázár
- Department of Surgery, University of Szeged, Pf. 427, Szeged 6701, Hungary
| | - Tibor Wittmann
- First Department of Medicine, University of Szeged, Korányi Fasor 8-10, Szeged 6720, Hungary
| | - Tamás Molnár
- First Department of Medicine, University of Szeged, Korányi Fasor 8-10, Szeged 6720, Hungary
| | - Richárd Róka
- First Department of Medicine, University of Szeged, Korányi Fasor 8-10, Szeged 6720, Hungary
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Lack of association between human papillomavirus infection and colorectal cancer. GASTROENTEROLOGY REVIEW 2014; 9:280-4. [PMID: 25396002 PMCID: PMC4223116 DOI: 10.5114/pg.2014.46163] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/27/2013] [Revised: 01/28/2014] [Accepted: 02/23/2014] [Indexed: 12/23/2022]
Abstract
Introduction Colorectal cancer is the third leading cause of cancer-related deaths worldwide, with nearly one million new cases identified annually. Different factors might cause colorectal cancer, one of the most prevalent cancers among both men and women. Viral aetiology in cancerous malignancies is a very important issue and so far a number of viral strains have been identified as tumour oncogene viruses. Viral infections, such as human papillomavirus (HPV), have recently been suggested as a risk factor for colorectal cancer. However, the aetiology of the disease is still unknown. Aim To assessed the association between HPV infection and colorectal cancer. Material and methods In this study, 50 cancer tissue samples and 50 samples without colon cancer were studied in order to identify HPV through polymerase chain reaction (PCR). Of 42 adenocarcinomas, 10 were well differentiated, 30 moderated differentiated, and 2 were poorly differentiated. DNA extraction was verified by beta globin gene amplification; specific PCR was carried out based on HPV L1 consensus primers MY09/MY11. Results HPV DNA was not identified in any of the normal, adenocarcinoma, or adenoma samples. Conclusions In contrast with previous studies, the current research failed to establish a relationship between HPV infection and the incidence of colon cancer. Considering the existing inconsistencies, it is recommended that further studies be conducted with larger sample size.
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Fecal molecular markers for colorectal cancer screening. Gastroenterol Res Pract 2011; 2012:184343. [PMID: 22969796 PMCID: PMC3226355 DOI: 10.1155/2012/184343] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2011] [Accepted: 09/26/2011] [Indexed: 02/06/2023] Open
Abstract
Despite multiple screening techniques, including colonoscopy, flexible sigmoidoscopy, radiological imaging, and fecal occult blood testing, colorectal cancer remains a leading cause of death. As these techniques improve, their sensitivity to detect malignant lesions is increasing; however, detection of precursor lesions remains problematic and has generated a lack of general acceptance for their widespread usage. Early detection by an accurate, noninvasive, cost-effective, simple-to-use screening technique is central to decreasing the incidence and mortality of this disease. Recent advances in the development of molecular markers in faecal specimens are encouraging for its use as a screening tool. Genetic mutations and epigenetic alterations that result from the carcinogenetic process can be detected by coprocytobiology in the colonocytes exfoliated from the lesion into the fecal matter. These markers have shown promising sensitivity and specificity in the detection of both malignant and premalignant lesions and are gaining popularity as a noninvasive technique that is representative of the entire colon. In this paper, we summarize the genetic and epigenetic fecal molecular markers that have been identified as potential targets in the screening of colorectal cancer.
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Abstract
March is national colorectal cancer awareness month. It is estimated that as many as 60% of colorectal cancer deaths could be prevented if all men and women aged 50 years or older were screened routinely. In 2000, Katie Couric's televised colonoscopy led to a 20% increase in screening colonoscopies across America, a stunning rise called the "Katie Couric Effect". This event demonstrated how celebrity endorsement affects health behavior. Currently, discussion is ongoing about the optimal strategy for CRC screening, particularly the costs of screening colonoscopy. The current CRC screening guidelines are summarized in Table 2. Debates over the optimum CRC screening test continue in the face of evidence that 22 million Americans aged 50 to 75 years are not screened for CRC by any modality and 25,000 of those lives may have been saved if they had been screened for CRC. It is clear that improving screening rates and reducing disparities in underscreened communities and population subgroups could further reduce colorectal cancer morbidity and mortality. National Institutes of Health consensus identified the following priority areas to enhance the use and quality of colorectal cancer screening: Eliminate financial barriers to colorectal cancer screening and appropriate follow-up of positive results of colorectal cancer screening. Develop systems to ensure the high quality of colorectal cancer screening programs. Conduct studies to determine the comparative effectiveness of the various colorectal cancer screening methods in usual practice settings. Encouraging population adherence to screening tests and allowing patients to select the tests they prefer may do more good (as long as they choose something) than whatever procedure is chosen by the medical profession as the preferred test.
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Affiliation(s)
- Jin He
- Department of Surgery, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287, USA
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Bünger S, Haug U, Kelly FM, Klempt-Giessing K, Cartwright A, Posorski N, Dibbelt L, Fitzgerald SP, Bruch HP, Roblick UJ, von Eggeling F, Brenner H, Habermann JK. Toward standardized high-throughput serum diagnostics: multiplex-protein array identifies IL-8 and VEGF as serum markers for colon cancer. ACTA ACUST UNITED AC 2011; 16:1018-26. [PMID: 21807963 DOI: 10.1177/1087057111414894] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Development and progression of colon cancer may be related to cytokines. Cytokines with diagnostic value have been identified individually but have not been implemented into clinical praxis. Using a multiplex protein array, the authors explore a panel of cytokines simultaneously and compared its performance to carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). Serum concentrations of 12 cytokines were simultaneously determined by multiplex biochip technology in 50 colon cancer patients and 50 healthy controls. Serum levels of interleukin-8 (IL-8) and CEA were significantly higher in cancer patients than in healthy controls. Areas under the receiver operating characteristic curves (AUCs) were largest for IL-8, followed by CEA, vascular endothelial growth factor (VEGF), and CA 19-9. Analyses regarding marker combinations showed an advantage over single marker performance for CEA, VEGF, and CA 19-9 but not for IL-8. Multiplex biochip array technology represents a practical tool in cytokine and cancer research when simultaneous determination of different biomarkers is of interest. The results suggest that the assessment of IL-8, CEA, VEGF, and possibly CA 19-9 serum levels could be useful for colon cancer screening with the potential of also detecting early stage tumors. Further validation studies using these and additional markers on a multiplex array format are encouraged.
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Affiliation(s)
- Stefanie Bünger
- Laboratory for Surgical Research, Department of Surgery, University of Lübeck, Germany
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Abstract
Colorectal cancer (CRC) is the most common cancer in the Nordic countries after breast and prostate cancer. About 15,000 new cancers are diagnosed and more than 7000 patients will die from CRC in 2005. CRC fulfils most of the criteria for applying screening; the natural history is well known compared with many other cancers. CRC may be cured by detection at an early stage and even prevented by removal of possible precursors like adenomas. Faecal occult blood test is the only CRC screening modality that has been subjected to adequately sized randomised controlled trials (RCT) with long-term follow-up results, using Hemoccult-II. Sensitivity for strictly asymptomatic CRC is less than 30% for a single screening round, but programme sensitivity has been estimated to be more. Biennial screening with un-rehydrated Hemoccult-II slides has shown a CRC mortality reduction of 15-18% after approximately 10 years of follow-up in those targeted for screening. For those attending, the mortality reduction has been estimated at 23%. Denmark has decided to do feasibility studies to try to evaluate whether a population-based screening run by the community will have the same effect as has been demonstrated in the randomised trials. In Norway the government has accepted no formal population-based screening. In Finland, the Ministry of Social Affairs and Health made a recommendation in 2003 to the municipalities to run a randomised feasibility study with FOBT screening for colorectal cancer as a public health policy that is repeated every second year. In 2004 the first municipalities started. It has been claimed that today Sweden cannot afford CRC screening despite the potential mortality benefit. There is sufficient evidence for the efficacy of screening for colorectal cancer with fecal occult blood test every second year. There is, however, only little evidence on the effectiveness of screening when run as a public health service and there is insufficient knowledge of harmful effects and costs, even in RCTs.
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Affiliation(s)
- Matti Hakama
- Finnish Cancer Registry Institute for Statistical and Epidemiological Cancer research, Helsinki, Finland.
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An SW, Kim NK, Chung HC. Genetic and epigenetic marker-based DNA test of stool is a promising approach for colorectal cancer screening. Yonsei Med J 2009; 50:331-4. [PMID: 19568592 PMCID: PMC2703753 DOI: 10.3349/ymj.2009.50.3.331] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2009] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignancies and leading cause of cancer-related deaths in the world.1 However, it may be treated effectively by surgical removal of the cancerous tissue if detected at early stages. Conventional tools for screening CRC are either invasive or inaccurate. Therefore, there is an urgent need to develop a reliable screening tools for CRC to significantly reduce its morbidity. In this regard, a novel DNA markers-based detection in stool is emerging as a promising approach.
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Affiliation(s)
- Sung Whan An
- Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul, Korea.
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Monleón D, Morales JM, Barrasa A, López JA, Vázquez C, Celda B. Metabolite profiling of fecal water extracts from human colorectal cancer. NMR IN BIOMEDICINE 2009; 22:342-8. [PMID: 19006102 DOI: 10.1002/nbm.1345] [Citation(s) in RCA: 142] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
Colorectal cancer is the second leading cause of cancer death in developed countries. There is a need for better preventive strategies to improve the outcome of this disease. The increasing availability of high-throughput methodologies opens up new possibilities for screening new markers. The application of NMR metabolic profiling to fecal water extracts has interesting potential as a diagnostic tool for detecting colorectal cancer. We obtained NMR metabolic profiles of fecal water extracts from patients with colorectal cancer and healthy individuals, to characterize possible differences between them and to identify potential diagnostic markers. Our results show that metabolic profiling of fecal water extracts is a cheap, reproducible and effective method for detecting colorectal cancer markers and therefore complements other stool-screening methods. A low concentration of short-chain fatty acids, such as acetate and butyrate, previously associated with the development of colorectal cancer, appears to be the most effective marker. Concentrations of proline and cysteine, which are major components of most colonic epithelium mucus glycoproteins, also display significant changes in samples from colorectal cancer. Differentiation between fecal water extracts from controls and patients with colorectal cancer by NMR spectroscopy combined with chemometric techniques opens up new possibilities for developing new, efficient, high-throughput screening protocols.
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Affiliation(s)
- Daniel Monleón
- Fundación de Investigación del Hospital Clínico Universitario de Valencia, Valencia, Spain.
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Burnett-Hartman AN, Newcomb PA, Potter JD. Infectious agents and colorectal cancer: a review of Helicobacter pylori, Streptococcus bovis, JC virus, and human papillomavirus. Cancer Epidemiol Biomarkers Prev 2009; 17:2970-9. [PMID: 18990738 DOI: 10.1158/1055-9965.epi-08-0571] [Citation(s) in RCA: 104] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Based on the high volume of bacteria and viruses that the intestine is exposed to and the importance of infectious agents in some gastrointestinal and anogenital cancers, it is not surprising the many studies have evaluated the association between colorectal cancer and infectious agents. This review highlights investigations of four agents in relation to colorectal cancer. Helicobacter pylori, Streptococcus bovis, JC virus, and human papillomavirus have all been evaluated as possible etiologic agents for colorectal cancer. For each of these agents, a review of possible mechanisms for carcinogenesis and epidemiologic evidence is discussed, and future directions for research are proposed.
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Affiliation(s)
- Andrea N Burnett-Hartman
- Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109, USA.
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12
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Abstract
Colorectal cancer ranks highly amongst all cancer sites in incidence and contributes to a substantial number of cancer related deaths in the United Kingdom. However, screening of average risk individuals has been shown to reduce both disease associated mortality and incidence. This paper provides an overview of both current and future screening methods for colorectal cancer, as well as current practice for screening in both average and high risk individuals.
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Affiliation(s)
- SA Goodbrand
- Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Dundee, DD1 9SY
| | - RJC Steele
- Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Dundee, DD1 9SY
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13
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Abstract
AIMS Screening and prevention of colorectal cancer (CRC) is a public health priority. Recent progress in understanding the biology of CRC has lead to possible new approaches to screening. In particular, assay of faecal molecular markers represents a promising non-invasive approach to screening, with improved safety, accuracy and patient compliance. METHODS MEDLINE/PubMed searches were used to identify key articles relating to faecal-based screening with secondary review of cited publications. RESULTS Faecal markers of CRC can be broadly divided into DNA based and non-DNA based. CONCLUSIONS Faecal occult blood testing for CRC screening has been advocated for decades for its non-invasiveness and low cost. It has exhibited a 15-33% decrease in mortality, despite drawbacks with sensitivity and compliance. Other non-DNA markers have the adequate sensitivity for inflammatory lesions but do not have the required specificity for screening average-risk populations. Faecal DNA testing has the potential to enhance the performance characteristics of stool testing. Because of molecular heterogeneity of cancer, no single DNA marker has yielded adequate sensitivity. Analysis of several combinations of markers in studies have produced high detection rates of both CRC and advanced adenomas in selected patient groups. However, the currently available markers, both non-DNA and DNA, have not yet been validated in large-scale studies screening average -risk population nor have they so far shown the necessary sensitivity and specificity required for large-scale screening programmes. Another major drawback with the DNA-based markers is the cost-effectiveness. Issues regarding implementation and compliance remain unanswered. These critical problems have to be rectified before these techniques can be recommended for large-scale CRC screening.
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Affiliation(s)
- A Loganayagam
- Department of Gastroenterology, King's College Hospital, Denmark Hill, London, UK.
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14
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Adams BD, McHugh KJA, Bryson SA, Dabulewicz J. The Law of Unintended Consequences: The Joint Commission Regulations and the Digital Rectal Examination. Ann Emerg Med 2008; 51:197-201, 201.e1. [DOI: 10.1016/j.annemergmed.2007.07.022] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2006] [Revised: 05/22/2007] [Accepted: 07/16/2007] [Indexed: 12/01/2022]
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Habermann JK, Bader FG, Franke C, Zimmermann K, Gemoll T, Fritzsche B, Ried T, Auer G, Bruch HP, Roblick UJ. From the genome to the proteome--biomarkers in colorectal cancer. Langenbecks Arch Surg 2007; 393:93-104. [PMID: 17938952 DOI: 10.1007/s00423-007-0230-1] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2007] [Accepted: 06/26/2007] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Colorectal cancer is the second leading cause of cancer-related death. Current clinical practice in colorectal cancer screening (fecal occult blood test, FOBT; colonoscopy) has contributed to a reduction of mortality. However, despite these screening programs, about 70% of carcinomas are detected at advanced tumor stages (UICC III/IV) presenting poor patient prognosis. Thus, innovative tools and methodologies for early cancer detection can directly result in improving patient survival rates. PATIENTS/METHODS Biomedical research has advanced rapidly in recent years with the availability of technologies such as global gene and protein expression profiling. Comprehensive tumor profiling has become a field of intensive research aiming at identifying biomarkers relevant for improved diagnostics and therapeutics. RESULTS In this paper, we report a comprehensive review of genomic, transcriptomic, and proteomic approaches for biomarker identification in tissue and blood with a main emphasis on two-dimensional gel-electrophoresis (2-DE) and mass spectrometry analyses. CONCLUSION Proteomics-based technologies enable to distinguish the healthy patient from the tumor patient with high sensitivity and specificity and could greatly improve common classification systems and diagnostics. However, this progress has not yet been transferred from bench to bedside but could open the door to a more accurate and target specific personalized medicine with improved patient survival.
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Affiliation(s)
- Jens K Habermann
- Department of Surgery, University of Schleswig-Holstein Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
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Mak T, Speake D, Lalloo F, Hill J, Evans DGR. Familial colorectal cancer referral to regional genetics department--a single centre experience. Fam Cancer 2007; 6:81-7. [PMID: 17160434 DOI: 10.1007/s10689-006-9108-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2006] [Accepted: 10/09/2006] [Indexed: 12/11/2022]
Abstract
Evaluation of familial colorectal cancer referral can assist in the planning of future cancer surveillance. The aim of the study is to assess colorectal cancer referral pattern to our regional genetics service. Hospital computer records and/or department referral books were used to identify cases referred to the regional genetic service during a 10-year period (1992-2001 inclusive). All files were reviewed along with associated demographic data, risk assessments, referral details, results from mutation testing and screening recommendations. In terms of result, a total of 1100 family files were reviewed (Familial Adenomatous Polyposis families were in a separate register). The number of referrals showed a 10-fold increase over the 10 years. 171 (15.6%) of families met the Amsterdam criteria II were classified as high-risk, 589 (53.5%) families were classified as moderate-risk and 337 (31.0%) as average or low risk. 22.9% families were referred with inaccurate cancer history. Sixty-one families have been identified with mismatch repair mutations. 56.8% of referred individuals were recommended to have regular colonoscopy ranging from 18 monthly to 5 yearly depending on their risks. In conclusion, there has been a 10-fold increase in individuals with suspected hereditary bowel cancer referred to the North West Regional Genetics Service in the last ten years. Genetic assessment may reduce the number of low-risk individuals and those who were found not to be mutation carriers from having unnecessary colonoscopic screening. Thus genetic risk assessment should precede the initiation of regular endoscopic screening.
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Affiliation(s)
- Tony Mak
- Department of Colorectal Surgery, Manchester Royal Infirmary, UK.
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Abstract
Colorectal cancer remains a leading cancer killer worldwide. The disease is both curable and preventable, and yet the importance of widespread screening is only now starting to be appreciated. This article reviews the variety of diagnostic tests, imaging procedures and endoscopic examinations available to detect colorectal cancer and polyps in their early stage and also presents details on various screening options. The critical role of the radiologist is elaborated on including accurate assessment of the tumor extent within the bowel wall and beyond and the detection of lymph node and distant metastases. Staging with CT, MR imaging, endorectal ultrasound, and positron emission tomography are of paramount importance in determining the most appropriate therapy and the risk of tumor recurrence and overall prognosis.
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Affiliation(s)
- Marc J Gollub
- Department of Radiology, Weill Medical College of Cornell University, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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Habermann JK, Roblick UJ, Luke BT, Prieto DA, Finlay WJJ, Podust VN, Roman JM, Oevermann E, Schiedeck T, Homann N, Duchrow M, Conrads TP, Veenstra TD, Burt SK, Bruch HP, Auer G, Ried T. Increased serum levels of complement C3a anaphylatoxin indicate the presence of colorectal tumors. Gastroenterology 2006; 131:1020-9; quiz 1284. [PMID: 17030172 PMCID: PMC2532535 DOI: 10.1053/j.gastro.2006.07.011] [Citation(s) in RCA: 70] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2006] [Accepted: 06/15/2006] [Indexed: 12/02/2022]
Abstract
BACKGROUND & AIMS Late diagnosis of colorectal carcinoma results in a significant reduction of average survival times. Yet despite screening programs, about 70% of tumors are detected at advanced stages (International Union Against Cancer stages III/IV). We explored whether detection of malignant disease would be possible through identification of tumor-specific protein biomarkers in serum samples. METHODS A discovery set of sera from patients with colorectal malignancy (n = 58) and healthy control individuals (n = 32) were screened for potential differences using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Candidate proteins were identified and their expression levels were validated in independent sample sets using a specific immunoassay (enzyme-linked immunosorbent assay). RESULTS By using class comparison and custom-developed algorithms we identified several m/z values that were expressed differentially between the malignant samples and the healthy controls of the discovery set. Characterization of the most prominent m/z values revealed a member of the complement system, the stable form of C3a anaphylatoxin (ie, C3a-desArg). Based on a specific enzyme-linked immunosorbent assay, serum levels of complement C3a-desArg predicted the presence of colorectal malignancy in a blinded validation set (n = 59) with a sensitivity of 96.8% and a specificity of 96.2%. Increased serum levels were also detected in 86.1% of independently collected sera from patients with colorectal adenomas (n = 36), whereas only 5.6% were classified as normal. CONCLUSIONS Complement C3a-desArg is present at significantly higher levels in serum from patients with colorectal adenomas (P < .0001) and carcinomas (P < .0001) than in healthy individuals. This suggests that quantification of C3a-desArg levels could ameliorate existing screening tests for colorectal cancer.
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Affiliation(s)
- Jens K. Habermann
- Genetics Branch, National Cancer Institute, NIH, Bethesda, MD, USA
- Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, Germany
- Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
| | - Uwe J. Roblick
- Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, Germany
- Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
| | - Brian T. Luke
- Advanced Biomedical Computing Center, SAIC-Frederick, Inc., NCI Frederick, Frederick, MD, USA
| | - DaRue A. Prieto
- Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., NCI Frederick, Frederick, MD, USA
| | - William J. J. Finlay
- Biomedical Diagnostics Group, Dublin City University, Dublin, Republic Of Ireland
| | | | - John M. Roman
- Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., NCI Frederick, Frederick, MD, USA
| | - Elisabeth Oevermann
- Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, Germany
| | - Thomas Schiedeck
- Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, Germany
| | - Nils Homann
- Internal Medicine Department, University of Schleswig-Holstein, Campus Lübeck, Germany
| | - Michael Duchrow
- Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, Germany
| | - Thomas P. Conrads
- Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., NCI Frederick, Frederick, MD, USA
| | - Timothy D. Veenstra
- Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick, Inc., NCI Frederick, Frederick, MD, USA
| | - Stanley K. Burt
- Advanced Biomedical Computing Center, SAIC-Frederick, Inc., NCI Frederick, Frederick, MD, USA
| | - Hans-Peter Bruch
- Department of Surgery, University of Schleswig-Holstein, Campus Lübeck, Germany
| | - Gert Auer
- Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden
| | - Thomas Ried
- Genetics Branch, National Cancer Institute, NIH, Bethesda, MD, USA
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Chen SC, Yen ZS, Wang HP, Lee CC, Hsu CY, Chen WJ, Hsu CY, Lai HS, Lin FY, Chen WJ. Ultrasonography in diagnosing colorectal cancers in patients presenting with abdominal distension. Med J Aust 2006; 184:614-6. [PMID: 16803440 DOI: 10.5694/j.1326-5377.2006.tb00415.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2005] [Accepted: 03/21/2006] [Indexed: 11/17/2022]
Abstract
OBJECTIVE To determine the usefulness of abdominal ultrasonography for diagnosing colorectal cancer in patients presenting with abdominal distension. DESIGN, SETTING AND PARTICIPANTS A prospective case series of consecutive adult patients with abdominal distension admitted to the National Taiwan University Hospital between January 2001 and July 2004. All participants were examined by abdominal ultrasonography. Those with suspected colorectal tumours on ultrasonography had follow-up colonoscopy, while all other patients had computed tomography scans. MAIN OUTCOME MEASURES Accuracy of abdominal ultrasonography for diagnosing colorectal cancer in patients with abdominal distension; incidence of colorectal cancer. RESULTS Of 511 patients eligible for inclusion in our study, 97 (19.0%) were confirmed to have colorectal cancer. For diagnosis of colorectal cancer, ultrasonography had a sensitivity of 92.8% (95% CI, 85.2%-96.8%); a specificity of 98.8% (95% CI, 97.0%-99.6%); a positive predictive value of 94.7% (95% CI, 87.6%-98.0%); a negative predictive value of 98.3% (95% CI 96.4%-99.3%); and an accuracy of 97.7%. CONCLUSION Ultrasonography is a sensitive tool for diagnosing colorectal cancer in patients presenting with abdominal distension.
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Affiliation(s)
- Shyr-Chyr Chen
- National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
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Ferretti G, Felici A, Ciccarese M, Papaldo P, Carlini P, Fabi A, Gelibter A, Cognetti F. Molecular stool testing for the early detection of colorectal cancer: swan song for p53? Ann Oncol 2006; 17:1026. [PMID: 16291578 DOI: 10.1093/annonc/mdj081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Pan ZZ, Wan DS, Zhang CQ, Shao JY, Li LR, Chen G, Zhou ZW, Wang FL. Using p53-immunostained large specimens to determine the distal intramural spread margin of rectal cancer. World J Gastroenterol 2006; 12:1626-9. [PMID: 16570359 PMCID: PMC4124299 DOI: 10.3748/wjg.v12.i10.1626] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the distal intramural spread (DIS) margin of rectal cancer.
METHODS: Sixty-one p53-positive specimens of rectal cancer were used. After conventional hematoxylin and eosin (H&E) staining, the DIS margin of rectal cancer in large specimens was examined by immunohistochemistry. The patients were divided into A, B, C, and D groups. After a long-term follow-up, the survival curves of the four groups were estimated using the life table.
RESULTS: Fifty-one of the sixty-one cases (83.6%) had DIS. The extent of DIS ranged 0.11-3.5 cm; meanwhile the mean of DIS measured by H&E staining was 0.13 cm. The significant difference was found between the means (t=5.622, P<0.0001). Only 1 of 51 patients had DIS greater than 3 cm. The DIS was less than 1.0 cm in most rectal cancer patients. The long-term results indicated that the survival rate of the patients whose DIS was greater than 1.0 cm was lower than that of the patients whose DIS was less than 0.5 cm.
CONCLUSION: Rectal cancer patients with DIS greater than 1.0 cm have poor prognosis.
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Affiliation(s)
- Zhi-Zhong Pan
- Department of Abdominal Surgery, Cancer Center, Sun Yat-Sen University, 651 Dongfeng Road, Guangzhou 510060, Guangdong Province, China.
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