title: Familial colorectal cancer, can it be identified by microsatellite instability and chromosomal instability? - A case-control study.
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.
authors.affiliation: Oncogenetic Clinic, Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark. lone.sunde@gmail.com
authors.forename: Lone
authors.initials: L
authors.lastname: Sunde
authors.forename: Marie Luise
authors.initials: ML
authors.lastname: Bisgaard
authors.forename: Helle
authors.initials: H
authors.lastname: Soll-Johanning
authors.forename: Niels Otto
authors.initials: NO
authors.lastname: Jacobsen
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.forename: Jan
authors.initials: J
authors.lastname: Skouv
authors.forename: Elsebeth
authors.initials: E
authors.lastname: Lynge
mesh_terms: D016022:Case-Control Studies; D043171:Chromosomal Instability; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005192:Family Health; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged