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A genome wide linkage analysis in Swedish families with hereditary non-familial adenomatous polyposis/non-hereditary non-polyposis colorectal cancer

¹ Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
² Division of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden

Correspondence to:
Correspondence to:
Professor A Lindblom
Department of Molecular Medicine and Surgery, CMM L8:02, Karolinska Hospital, S-171 76 Stockholm, Sweden; Annika.Lindblom{at}cmm.ki.se

ABSTRACT
Background and aim: Known colorectal cancer syndromes, such as familial adenomatous polyposis and hereditary non-polyposis colorectal cancer, have been identified in only a small proportion of cases with a family history of disease. In an attempt to identify loci harbouring novel predisposing genes, we have performed a genome wide linkage analysis in 18 colorectal cancer families recruited from the Department of Clinical Genetics at Karolinska Hospital, Sweden.

Methods: Multipoint parametric and non-parametric linkage analyses were performed using two affected status criteria, stringent and less stringent. Parametric analysis was performed under the assumption of locus homogeneity and locus heterogeneity.

Results: The initial scan performed using the less stringent affected status criteria revealed regions of interest on chromosome 11 (marker D11S1314: heterogeneity logarithm of odds (HLOD) score 1.96, non-parametric LOD (NPL) score 1.28; and marker D11S908: HLOD score 2.10, NPL score 2.16) and chromosome 14 (marker D14S258: HLOD score 2.61, NPL score 2.88). Using the stringent affected status criteria, a locus on chromosome 22 was suggested in the parametric analysis (marker D22S315: HLOD score 1.26). After finemapping of the regions on chromosomes 11 and 14, HLOD and NPL scores were reduced but still within the range of suggestive linkage. Haplotype analysis revealed overlapping regions between D11S987 and D11S4207 (proximal region), D11S4120 and D11S4090 (distal region), on chromosome 11, and between D14S1038 and D14S1069 on chromosome 14.

Conclusion: Our study provides evidence of genetic heterogeneity among Swedish colorectal cancer families. Three novel regions were suggested to be of interest in a proportion of families analysed. Further studies are needed to confirm this result.

Keywords: linkage analysis; hereditary non-polyposis colorectal cancer; familial adenomatous polyposis; colorectal cancer; chromosome 11; chromosome 14; chromosome 22

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