|Grant Number:||5R01CA104667-03 Interpret this number|
|Primary Investigator:||Potter, John|
|Organization:||Fred Hutchinson Cancer Research Center|
|Project Title:||Genetic Linkage in Colorectal Cancer Familes|
DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is a common, serious disease that clusters in families, such that individuals with an affected sibling are at almost 3-fold increased risk compared to those in the general population. Little, if any, of the observed familial clustering has yet been explained by shared environmental exposures. Known genetic syndromes such as hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP) are thought to account for less than 2% of cases. Unidentified susceptibility loci are probably important in much of the remaining non-syndromic familial colorectal cancer. We aim to identify novel CRC susceptibility loci collected via the Colon Cancer Cooperative Family Registry (Colon CFR). The Colon CFR is an NCI-supported consortium initiated in 1997 that has established a comprehensive collaborative infrastructure for interdisciplinary studies in CRC genetic epidemiology. Six cooperating registries have collected CRC tumor specimens, blood samples, and epidemiologic information from multiple-case families. Recruited CRC families from the Colon CFR, as well as from an additional site using identical protocols, who are not shown to carry HNPCC- or FAP-predisposing mutations will be included in a two-stage gene-mapping strategy. First, we will perform a genome-wide linkage analysis using 844 affected relative pairs in 499 families. Approximately 400 microsatellite markers will be genotyped and assessed for evidence of linkage to CRC using parametric and non-parametric methods; regions will be identified for follow-up. Second, individuals from 499 families will be genotyped using more densely-spaced microsatellite markers in genomic regions suggested by the initial scan. Parametric and non-parametric linkage methods will assess evidence for CRC linkage. Strengths of this effort include the use of an existing CRC family collection, a wealth of preliminary data (including screening for known mutations), and a successful collaborative history among investigators. A key future aim is to combine these families with those of other CRC linkage studies in the US and UK to amass an extensive resource with further increased power to understand CRC genetic susceptibility.
Identification of novel variants in colorectal cancer families by high-throughput exome sequencing.
Authors: DeRycke MS, Gunawardena SR, Middha S, Asmann YW, Schaid DJ, McDonnell SK, Riska SM, Eckloff BW, Cunningham JM, Fridley BL, Serie DJ, Bamlet WR, Cicek MS, Jenkins MA, Duggan DJ, Buchanan D, Clendenning M, Haile RW, Woods MO, Gallinger SN, Casey G, Potter JD, Newcomb PA, Le Marchand L, Lindor NM, Thibodeau SN, Goode EL
Source: Cancer Epidemiol Biomarkers Prev, 2013 Jul;22(7), p. 1239-51.
EPub date: 2013 May 1.
Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22.
Authors: Cicek MS, Cunningham JM, Fridley BL, Serie DJ, Bamlet WR, Diergaarde B, Haile RW, Le Marchand L, Krontiris TG, Younghusband HB, Gallinger S, Newcomb PA, Hopper JL, Jenkins MA, Casey G, Schumacher F, Chen Z, DeRycke MS, Templeton AS, Winship I, Green RC, Green JS, Macrae FA, Parry S, Young GP, Young JP, Buchanan D, Thomas DC, Bishop DT, Lindor NM, Thibodeau SN, Potter JD, Goode EL, Colon CFR
Source: PLoS One, 2012;7(5), p. e38175.
EPub date: 2012 May 31.
Bayesian mixture models for the incorporation of prior knowledge to inform genetic association studies.
Authors: Fridley BL, Serie D, Jenkins G, White K, Bamlet W, Potter JD, Goode EL
Source: Genet Epidemiol, 2010 Jul;34(5), p. 418-26.
Confirmation of linkage to and localization of familial colon cancer risk haplotype on chromosome 9q22.
Authors: Gray-McGuire C, Guda K, Adrianto I, Lin CP, Natale L, Potter JD, Newcomb P, Poole EM, Ulrich CM, Lindor N, Goode EL, Fridley BL, Jenkins R, Le Marchand L, Casey G, Haile R, Hopper J, Jenkins M, Young J, Buchanan D, Gallinger S, Adams M, Lewis S, Willis J, Elston R, Markowitz SD, Wiesner GL
Source: Cancer Res, 2010 Jul 1;70(13), p. 5409-18.
EPub date: 2010 Jun 15.
Variants on 9p24 and 8q24 are associated with risk of colorectal cancer: results from the Colon Cancer Family Registry.
Authors: Poynter JN, Figueiredo JC, Conti DV, Kennedy K, Gallinger S, Siegmund KD, Casey G, Thibodeau SN, Jenkins MA, Hopper JL, Byrnes GB, Baron JA, Goode EL, Tiirikainen M, Lindor N, Grove J, Newcomb P, Jass J, Young J, Potter JD, Haile RW, Duggan DJ, Le Marchand L, Colon CFR
Source: Cancer Res, 2007 Dec 1;67(23), p. 11128-32.
Bias of allele-sharing linkage statistics in the presence of intermarker linkage disequilibrium.
Authors: Goode EL, Badzioch MD, Jarvik GP
Source: BMC Genet, 2005 Dec 30;6 Suppl 1, p. S82.
EPub date: 2005 Dec 30.