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


CONCLUSIONS
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.
Picelli
Simone
S
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. simone.picelli@ki.se
Vandrovcova
Jana
J
Jones
Siân
S
Djureinovic
Tatjana
T
Skoglund
Johanna
J
Zhou
Xiao-Lei
XL
Velculescu
Victor E
VE
Vogelstein
Bert
B
Lindblom
Annika
A
D000368:Aged; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D008297:Male; D008875:Middle Aged; D013548:Sweden