Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan.
To identify a novel susceptibility gene for colorectal cancer (CRC), we conducted a genome-wide linkage analysis of 69 pedigrees segregating colorectal neoplasia in which involvement of known loci had been excluded, using a high-density single nucleotide polymorphism (SNP) array containing 10,204 markers. Multipoint linkage analyses were undertaken using both non-parametric (model-free) and parametric (model-based) methods. After the removal of SNPs in strong linkage disequilibrium, we obtained a maximum non-parametric linkage statistic of 3.40 (P=0.0003) at chromosomal region 3q21-q24. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a dominant model (HLOD=3.10, genome-wide P=0.038) with 62% of families linked to the locus. We provide evidence for a novel CRC susceptibility gene. Further studies are needed to confirm this localization and to evaluate the contribution of this locus to disease incidence.
Kemp
Zoe
Z
Molecular and Population Genetics Laboratory, Cancer Research UK, London, UK.
Carvajal-Carmona
Luis
L
Spain
Sarah
S
Barclay
Ella
E
Gorman
Margaret
M
Martin
Lynn
L
Jaeger
Emma
E
Brooks
Neil
N
Bishop
D Timothy
DT
Thomas
Huw
H
Tomlinson
Ian
I
Papaemmanuil
Elli
E
Webb
Emily
E
Sellick
Gabrielle S
GS
Wood
Wendy
W
Evans
Gareth
G
Lucassen
Anneke
A
Maher
Eamonn R
ER
Houlston
Richard S
RS
D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008126:Lod Score; D008297:Male; D008957:Models, Genetic; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors