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Article type: Research Article
Authors: Sunde, Lonea; * | Bisgaard, Marie Luiseb | Soll-Johanning, Hellec; d | Jacobsen, Niels Ottoe | Bolund, Larsf | Skouv, Jang | Lynge, Elsebethh
Affiliations: [a] Oncogenetic Clinic, Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark | [b] Institute for Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark | [c] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark | [d] National Research Centre for the Working Environment, Copenhagen, Denmark | [e] Department of Pathology, Aarhus University Hospital, Aarhus, Denmark | [f] Institute of Human Genetics, University of Aarhus, Aarhus, Denmark | [g] Chr. Hansen Holding, Hoersholm, Denmark | [h] Institute of Public Health, Department of Epidemiology, University of Copenhagen, Copenhagen, Denmark
Correspondence: [*] Corresponding author: Lone Sunde, Oncogenetic Clinic, Department of Clinical Genetics, Aarhus University Hospital, The Bartholin Building, University of Aarhus, DK-8000 Aarhus, Denmark. Tel.: +45 8949 4364; Fax: +45 8949 4370; E-mail: [email protected].
Abstract: Colonoscopy is recommended for persons with a familial risk of colorectal cancer (CRC). A familial risk is identified by a family history with CRC and/or predisposing mutation(s). However, such information may not be available. We analysed whether MSI (MicroSatellite Instability) and/or CIN (Chromosome INstability=LOH (loss of heterozygosity) and/or DNA-aneuploidy (abnormal nuclear DNA contents)) could be used as predictors of familial CRC. Formalin-fixed tissue from 97 patients with CRC (29 patients with 2 or more affected first-degree relatives (="cases"), 29 matched CRC controls without a family history, and 39 relatives to cases) were analysed for MSI and CIN. In this small case-control study, no significant differences in the frequencies of MSI and CIN were observed between cases with a family history and their controls without a family history. MSI+;CIN- was observed in 6/29 cases and in 0/29 controls (p=0.02), most frequently in cases with affected siblings, only (3/7). However, for 13 patients from whom several CRC tumours were analysed, concordant results for MSI/LOH/DNA-ploidy were obtained only in 10/9/9. Among cases and relative(s), concordant results for MSI, LOH and DNA-ploidy were obtained in 16/26, 16/26, and 14/25 families, respectively. Although MSI+;CIN- appeared to predict familial CRC with a high specificity, neither MSI, CIN, or MSI+;CIN- are likely to be sufficiently sensitive predictors of familial CRC.
Keywords: Chromosomal instability (CIN), DNA-ploidy, familial colorectal neoplasms, Loss of heterozygosity (LOH), Microsatellite instability (MSI), flow fluorometry
DOI: 10.3233/CBM-2009-0104
Journal: Cancer Biomarkers, vol. 5, no. 4-5, pp. 197-205, 2009
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