title: Confirmation of linkage to and localization of familial colon cancer risk haplotype on chromosome 9q22.
abstract: Genetic risk factors are important contributors to the development of colorectal cancer. Following the definition of a linkage signal at 9q22-31, we fine mapped this region in an independent collection of colon cancer families. We used a custom array of single-nucleotide polymorphisms (SNP) densely spaced across the candidate region, performing both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. Through this approach, we isolated the association effect to a five-SNP haplotype centered at 98.15 Mb on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to GALNT12, also recently shown to be altered in colon tumors. We used a predictive modeling algorithm to show the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (odds ratio, 3.68), and the accuracy of our prediction model (approximately 60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q.
authors.affiliation: Department of Arthritis and Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Gray-McGuire
authors.forename: Kishore
authors.initials: K
authors.lastname: Guda
authors.forename: Indra
authors.initials: I
authors.lastname: Adrianto
authors.forename: Chee Paul
authors.initials: CP
authors.lastname: Lin
authors.forename: Leanna
authors.initials: L
authors.lastname: Natale
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Polly
authors.initials: P
authors.lastname: Newcomb
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Poole
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Ulrich
authors.forename: Noralane
authors.initials: N
authors.lastname: Lindor
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Robert
authors.initials: R
authors.lastname: Jenkins
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: Robert
authors.initials: R
authors.lastname: Haile
authors.forename: John
authors.initials: J
authors.lastname: Hopper
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkins
authors.forename: Joanne
authors.initials: J
authors.lastname: Young
authors.forename: Daniel
authors.initials: D
authors.lastname: Buchanan
authors.forename: Steve
authors.initials: S
authors.lastname: Gallinger
authors.forename: Mark
authors.initials: M
authors.lastname: Adams
authors.forename: Susan
authors.initials: S
authors.lastname: Lewis
authors.forename: Joseph
authors.initials: J
authors.lastname: Willis
authors.forename: Robert
authors.initials: R
authors.lastname: Elston
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
authors.forename: Georgia L
authors.initials: GL
authors.lastname: Wiesner
mesh_terms: D002899:Chromosomes, Human, Pair 9; D003110:Colonic Neoplasms / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide