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

Mine Cicek, Julie M Cunningham, Brooke L. Fridley, Daniel J. Serie, William R. Bamlet, Brenda Diergaarde, Robert W. Haile, Loic Le Marchand, Theodore G. Krontiris, H. Banfield Younghusband, Steven Gallinger, Polly A. Newcomb, John L. Hopper, Mark A. Jenkins, Graham Casey, Fredrick Schumacher, Zhu Chen, Melissa S. DeRycke, Allyson S. Templeton, Ingrid WinshipRoger C. Green, Jane S. Green, Finlay A. Macrae, Susan Parry, Graeme P. Young, Joanne P. Young, Daniel Buchanan, Duncan C. Thomas, D. Timothy Bishop, Noralane Morey Lindor, Stephen N Thibodeau, John D. Potter, Ellen L Goode

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere38175
JournalPLoS One
Volume7
Issue number5
DOIs
StatePublished - May 31 2012

Fingerprint

DNA Mismatch Repair
Chromosomes
colorectal neoplasms
linkage (genetics)
Colorectal Neoplasms
Repair
Genes
chromosomes
Tumors
loci
neoplasms
Genome
Lod Score
Newfoundland and Labrador
Neoplasms
Microsatellite Instability
Polymorphism
genome
Microsatellite Repeats
Colonic Neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22. / Cicek, Mine; Cunningham, Julie M; Fridley, Brooke L.; Serie, Daniel J.; Bamlet, William R.; Diergaarde, Brenda; Haile, Robert W.; Le Marchand, Loic; Krontiris, Theodore G.; Younghusband, H. Banfield; Gallinger, Steven; Newcomb, Polly A.; Hopper, John L.; Jenkins, Mark A.; Casey, Graham; Schumacher, Fredrick; Chen, Zhu; DeRycke, Melissa S.; Templeton, Allyson S.; Winship, Ingrid; Green, Roger C.; Green, Jane S.; Macrae, Finlay A.; Parry, Susan; Young, Graeme P.; Young, Joanne P.; Buchanan, Daniel; Thomas, Duncan C.; Bishop, D. Timothy; Lindor, Noralane Morey; Thibodeau, Stephen N; Potter, John D.; Goode, Ellen L.

In: PLoS One, Vol. 7, No. 5, e38175, 31.05.2012.

Research output: Contribution to journalArticle

Cicek, M, 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 2012, 'Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22', PLoS One, vol. 7, no. 5, e38175. https://doi.org/10.1371/journal.pone.0038175
Cicek, Mine ; Cunningham, Julie M ; Fridley, Brooke L. ; Serie, Daniel J. ; Bamlet, William R. ; Diergaarde, Brenda ; Haile, Robert W. ; Le Marchand, Loic ; Krontiris, Theodore G. ; Younghusband, H. Banfield ; Gallinger, Steven ; Newcomb, Polly A. ; Hopper, John L. ; Jenkins, Mark A. ; Casey, Graham ; Schumacher, Fredrick ; Chen, Zhu ; DeRycke, Melissa S. ; Templeton, Allyson S. ; Winship, Ingrid ; Green, Roger C. ; Green, Jane S. ; Macrae, Finlay A. ; Parry, Susan ; Young, Graeme P. ; Young, Joanne P. ; Buchanan, Daniel ; Thomas, Duncan C. ; Bishop, D. Timothy ; Lindor, Noralane Morey ; Thibodeau, Stephen N ; Potter, John D. ; Goode, Ellen L. / Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22. In: PLoS One. 2012 ; Vol. 7, No. 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.",
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T1 - Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

AU - Cicek, Mine

AU - Cunningham, Julie M

AU - Fridley, Brooke L.

AU - Serie, Daniel J.

AU - Bamlet, William R.

AU - Diergaarde, Brenda

AU - Haile, Robert W.

AU - Le Marchand, Loic

AU - Krontiris, Theodore G.

AU - Younghusband, H. Banfield

AU - Gallinger, Steven

AU - Newcomb, Polly A.

AU - Hopper, John L.

AU - Jenkins, Mark A.

AU - Casey, Graham

AU - Schumacher, Fredrick

AU - Chen, Zhu

AU - DeRycke, Melissa S.

AU - Templeton, Allyson S.

AU - Winship, Ingrid

AU - Green, Roger C.

AU - Green, Jane S.

AU - Macrae, Finlay A.

AU - Parry, Susan

AU - Young, Graeme P.

AU - Young, Joanne P.

AU - Buchanan, Daniel

AU - Thomas, Duncan C.

AU - Bishop, D. Timothy

AU - Lindor, Noralane Morey

AU - Thibodeau, Stephen N

AU - Potter, John D.

AU - Goode, Ellen L

PY - 2012/5/31

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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.

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