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Can DNA sampling from the rectal mucosa be a novel tool for the detection of colorectal cancer?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
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2010 (English)In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 25, no 9, 1071-1078 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: The objective was to evaluate a new method for DNA sampling from the rectal mucosa for the detection of colorectal cancer or any clinically significant pathology in the colon and rectum. METHODS: This prospective cohort study included patients scheduled for colonoscopy (group 1, n = 185) or colonic resection because of suspected colorectal cancer (group 2, n = 62). A test instrument with a balloon-holding end was introduced through a proctoscope into the rectum to collect exfoliated cells, from which DNA was isolated and quantified. RESULTS: The detection of colorectal cancer in group 1 showed a sensitivity for the DNA cut-off levels 1.5, 2, and 2.5 microg/ml of 100%, 80%, and 60%, and a specificity of 37%, 46%, and 56%, respectively. In group 2, for the same cut-off levels, the sensitivity was 73%, 61%, and 55%, and the specificity was 67%, 67%, and 67%, respectively. CONCLUSIONS: This novel technique is a safe and easy way of collecting DNA from the rectal mucosa. The sensitivity and specificity of the test were too low to be acceptable for a screening test. The low sensitivity and specificity in this study could be explained by the diversity within the study groups as many patients presented with long-term history of colorectal disease and surgical interventions in the past.

Place, publisher, year, edition, pages
2010. Vol. 25, no 9, 1071-1078 p.
Keyword [en]
Colon cancer, Rectal cancer, Screening, Fecal DNA, Exfoliated colonocyte collection
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-133091DOI: 10.1007/s00384-010-0979-5ISI: 000280578500005PubMedID: 20563588OAI: oai:DiVA.org:uu-133091DiVA: diva2:360084
Available from: 2010-11-02 Created: 2010-11-02 Last updated: 2017-12-12Bibliographically approved
In thesis
1. Cancer of the Colon and Rectum: Prognostic Factors and Early Detection
Open this publication in new window or tab >>Cancer of the Colon and Rectum: Prognostic Factors and Early Detection
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Colorectal cancer (CRC) is one of the most common causes of death from malignant disease. Nevertheless, no ideal screening method exists and there is a lack of prognostic and predictive factors to support clinical decisions and to aid the development of a more individualized treatment for patients with CRC. The aim of this thesis was to investigate early detection, prognostic and predictive factors of CRC. In the first paper, a novel method to collect cells for DNA quantification from the rectal mucosa was investigated. The sensitivity and specificity of this test to detect CRC or any pathology in colon and rectum were ultimately too low to be acceptable. In the second paper, the prognostic value of growth differentiation factor 15 (GDF 15) was evaluated in patients curatively operated for colorectal cancer. GDF 15 expression was demonstrated to be associated with a negative prognosis in patients with stages I-III and III disease. In the third paper, the prognostic value of BRAF, PIK3CA KRAS and MSI was evaluated in a cohort of patients with CRC stratified by disease and recurrence. The results indicated that patients with CRC stage III without recurrence have a higher frequency of BRAF mutation compared to stage III patients with recurrence. In the fourth paper, histopathological predictors of pathologic complete response (pCR) as well as the association between pre-treatment carcinoembryonic antigen (CEA) levels and pCR in non-smoking and smoking patients receiving preoperative chemo-radiotherapy for rectal cancer were evaluated. Only in non-smokers was a low CEA level significantly associated with pCR, suggesting that the predictive value of CEA for pCR in rectal cancer in smokers can be limited. In sum, this research has investigated a new method for CRC detection and further evaluated the clinical use of prognostic and predictive markers in CRC.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 83 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 706
Keyword
colorectal cancer screening predictive markers prognostic markers
National Category
Surgery
Identifiers
urn:nbn:se:uu:diva-159142 (URN)978-91-554-8166-7 (ISBN)
Public defence
2011-11-04, Hedstrand salen, Akademiska sjuhuset, ing. 70 bv, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2011-10-14 Created: 2011-09-22 Last updated: 2012-06-14Bibliographically approved

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Wallin, UlrikGunnarsson, UlfPåhlman, Lars

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