Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

Cicek, MS and Cunningham, JM and Fridley, BL and Serie, DJ and Bamlet, WR and Diergaarde, B and Haile, RW and Le Marchand, L and Krontiris, TG and Younghusband, HB and Gallinger, S and Newcomb, PA and Hopper, JL and Jenkins, MA and Casey, G and Schumacher, F and Chen, Z and DeRycke, MS and Templeton, AS and Winship, I and Green, RC and Green, JS and Macrae, FA and Parry, S and Young, GP and Young, JP and Buchanan, D and Thomas, DC and Bishop, DT and Lindor, NM and Thibodeau, SN and Potter, JD and Goode, EL (2012) Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22. PLoS ONE, 7 (5).

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Abstract

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. © 2012 Cicek et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Cicek, MS Cunningham, JM Fridley, BL Serie, DJ Bamlet, WR Diergaarde, B bbd3@pitt.edu BBD3 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
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Lo, Anthony W. I. UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	31 May 2012
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	7
Number:	5
DOI or Unique Handle:	10.1371/journal.pone.0038175
Schools and Programs:	School of Public Health > Epidemiology
Refereed:	Yes
PubMed ID:	22675446
Date Deposited:	11 Jul 2012 18:09
Last Modified:	02 Feb 2019 15:55
URI:	http://d-scholarship.pitt.edu/id/eprint/12714

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