Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q

Simone Picelli, Jana Vandrovcova, Siân Jones, Tatjana Djureinovic, Johanna Skoglund, Xiao Lei Zhou, Victor E. Velculescu, Bert Vogelstein, Annika Lindblom

Research output: Contribution to journalArticle

Abstract

Background: Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Familial Adenomatous Polyposis (FAP). In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer. Methods: Statistical analysis was performed using multipoint parametric and nonparametric linkage. Results: Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1-q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD) = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL) = 2.1). Conclusion: The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q.

Original languageEnglish (US)
Article number87
JournalBMC cancer
Volume8
DOIs
StatePublished - Apr 1 2008

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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