TY - JOUR
T1 - Colorectal Cancer Linkage on Chromosomes 4q21, 8q13, 12q24, and 15q22
AU - Cicek, Mine
AU - Cunningham, Julie
AU - Fridley, Brooke
AU - Serie, Daniel
AU - Bamlet, William
AU - Diergaarde, Brenda
AU - Haile, Robert
AU - Le Marchand, Loic
AU - Krontiris, Theodore
AU - Banfield Younghusband, H
AU - Gallinger, Steven
AU - Newcomb, Polly
AU - Hopper, John
AU - Jenkins, Mark
AU - Casey, Graham
AU - Schumacher, Frederick
AU - Chen, Zhu
AU - DeRycke, Melissa
AU - Templeton, Allyson
AU - Winship, Ingrid
AU - Green, Roger
AU - Green, Jane
AU - Macrae, F
AU - Parry, Susan
AU - Young, Graeme
AU - Young, Joanne
AU - Buchanan, Daniel
AU - Thomas, Duncan
AU - Bishop, D
AU - Lindor, N
AU - Thibodeau, S
AU - Potter, J
AU - Goode, Ellen
PY - 2012/5/31
Y1 - 2012/5/31
N2 - A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated.
AB - A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated.
UR - http://www.scopus.com/inward/record.url?scp=84861655606&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0038175
DO - 10.1371/journal.pone.0038175
M3 - Article
SN - 1932-6203
VL - 7
SP - e38175
JO - PLoS One
JF - PLoS One
IS - 5
M1 - e38175
ER -