title: Evidence for a colorectal cancer susceptibility locus on chromosome 3q21-q24 from a high-density SNP genome-wide linkage scan.
abstract: 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.
authors.affiliation: Molecular and Population Genetics Laboratory, Cancer Research UK, London, UK.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Kemp
authors.forename: Luis
authors.initials: L
authors.lastname: Carvajal-Carmona
authors.forename: Sarah
authors.initials: S
authors.lastname: Spain
authors.forename: Ella
authors.initials: E
authors.lastname: Barclay
authors.forename: Margaret
authors.initials: M
authors.lastname: Gorman
authors.forename: Lynn
authors.initials: L
authors.lastname: Martin
authors.forename: Emma
authors.initials: E
authors.lastname: Jaeger
authors.forename: Neil
authors.initials: N
authors.lastname: Brooks
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Huw
authors.initials: H
authors.lastname: Thomas
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.forename: Elli
authors.initials: E
authors.lastname: Papaemmanuil
authors.forename: Emily
authors.initials: E
authors.lastname: Webb
authors.forename: Gabrielle S
authors.initials: GS
authors.lastname: Sellick
authors.forename: Wendy
authors.initials: W
authors.lastname: Wood
authors.forename: Gareth
authors.initials: G
authors.lastname: Evans
authors.forename: Anneke
authors.initials: A
authors.lastname: Lucassen
authors.forename: Eamonn R
authors.initials: ER
authors.lastname: Maher
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: 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