Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis

Nicola Whiffin, Fay J. Hosking, Susan M. Farrington, Claire Palles, Sara E. Dobbins, Lina Zgaga, Amy Lloyd, Ben Kinnersley, Maggie Gorman, Albert Tenesa, Peter Broderick, Yufei Wang, Ella Barclay, Caroline Hayward, Lynn Martin, Daniel D. Buchanan, Aung Ko Win, John Hopper, Mark Jenkins, Noralane Morey LindorPolly A. Newcomb, Steve Gallinger, David Conti, Fred Schumacher, Graham Casey, Tao Liu, Harry Campbell, Annika Lindblom, Richard S. Houlston, Ian P. Tomlinson, Malcolm G. Dunlop

Research output: Contribution to journalArticle

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Abstract

To identify common variants influencing colorectal cancer (CRC) risk, we performed a meta-analysis of five genome-wide association studies, comprising 5626 cases and 7817 controls of European descent. We conducted replication of top ranked single nucleotide polymorphisms (SNPs) in additional series totalling 14 037 cases and 15 937 controls, identifying a new CRC risk locus at 10q24.2 [rs1035209; odds ratio (OR) = 1.13, P = 4.54 × 10-11]. We also performed meta-analysis of our studies, with previously published data, of several recently purported CRC risk loci. We failed to find convincing evidence for a previously reported genomewide association at rs11903757 (2q32.3). Of the three additional loci for which evidence of an association in Europeans has been previously described we failed to show an association between rs59336 (12q24.21) and CRC risk. However, for the other two SNPs, our analyses demonstrated new, formally significant associations with CRC. These are rs3217810 intronic in CCND2 (12p13.32; OR = 1.19, P = 2.16 3 10-10) and rs10911251 near LAMC1 (1q25.3; OR = 1.09, P = 1.75 × 10-8). Additionally, we found some evidence to support a relationship between, rs647161, rs2423297 and rs10774214 and CRC risk originally identified in East Asians in our European datasets. Our findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CRC.

Original languageEnglish (US)
Article numberddu177
Pages (from-to)4729-4737
Number of pages9
JournalHuman Molecular Genetics
Volume23
Issue number17
DOIs
StatePublished - 2014

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Meta-Analysis
Colorectal Neoplasms
Genome
Odds Ratio
Single Nucleotide Polymorphism
Genome-Wide Association Study
Genetic Predisposition to Disease

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Whiffin, N., Hosking, F. J., Farrington, S. M., Palles, C., Dobbins, S. E., Zgaga, L., ... Dunlop, M. G. (2014). Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. Human Molecular Genetics, 23(17), 4729-4737. [ddu177]. https://doi.org/10.1093/hmg/ddu177

Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. / Whiffin, Nicola; Hosking, Fay J.; Farrington, Susan M.; Palles, Claire; Dobbins, Sara E.; Zgaga, Lina; Lloyd, Amy; Kinnersley, Ben; Gorman, Maggie; Tenesa, Albert; Broderick, Peter; Wang, Yufei; Barclay, Ella; Hayward, Caroline; Martin, Lynn; Buchanan, Daniel D.; Win, Aung Ko; Hopper, John; Jenkins, Mark; Lindor, Noralane Morey; Newcomb, Polly A.; Gallinger, Steve; Conti, David; Schumacher, Fred; Casey, Graham; Liu, Tao; Campbell, Harry; Lindblom, Annika; Houlston, Richard S.; Tomlinson, Ian P.; Dunlop, Malcolm G.

In: Human Molecular Genetics, Vol. 23, No. 17, ddu177, 2014, p. 4729-4737.

Research output: Contribution to journalArticle

Whiffin, N, Hosking, FJ, Farrington, SM, Palles, C, Dobbins, SE, Zgaga, L, Lloyd, A, Kinnersley, B, Gorman, M, Tenesa, A, Broderick, P, Wang, Y, Barclay, E, Hayward, C, Martin, L, Buchanan, DD, Win, AK, Hopper, J, Jenkins, M, Lindor, NM, Newcomb, PA, Gallinger, S, Conti, D, Schumacher, F, Casey, G, Liu, T, Campbell, H, Lindblom, A, Houlston, RS, Tomlinson, IP & Dunlop, MG 2014, 'Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis', Human Molecular Genetics, vol. 23, no. 17, ddu177, pp. 4729-4737. https://doi.org/10.1093/hmg/ddu177
Whiffin N, Hosking FJ, Farrington SM, Palles C, Dobbins SE, Zgaga L et al. Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. Human Molecular Genetics. 2014;23(17):4729-4737. ddu177. https://doi.org/10.1093/hmg/ddu177
Whiffin, Nicola ; Hosking, Fay J. ; Farrington, Susan M. ; Palles, Claire ; Dobbins, Sara E. ; Zgaga, Lina ; Lloyd, Amy ; Kinnersley, Ben ; Gorman, Maggie ; Tenesa, Albert ; Broderick, Peter ; Wang, Yufei ; Barclay, Ella ; Hayward, Caroline ; Martin, Lynn ; Buchanan, Daniel D. ; Win, Aung Ko ; Hopper, John ; Jenkins, Mark ; Lindor, Noralane Morey ; Newcomb, Polly A. ; Gallinger, Steve ; Conti, David ; Schumacher, Fred ; Casey, Graham ; Liu, Tao ; Campbell, Harry ; Lindblom, Annika ; Houlston, Richard S. ; Tomlinson, Ian P. ; Dunlop, Malcolm G. / Identification of susceptibility loci for colorectal cancer in a genome-wide meta-analysis. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 17. pp. 4729-4737.
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AU - Dobbins, Sara E.

AU - Zgaga, Lina

AU - Lloyd, Amy

AU - Kinnersley, Ben

AU - Gorman, Maggie

AU - Tenesa, Albert

AU - Broderick, Peter

AU - Wang, Yufei

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AU - Hayward, Caroline

AU - Martin, Lynn

AU - Buchanan, Daniel D.

AU - Win, Aung Ko

AU - Hopper, John

AU - Jenkins, Mark

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AU - Newcomb, Polly A.

AU - Gallinger, Steve

AU - Conti, David

AU - Schumacher, Fred

AU - Casey, Graham

AU - Liu, Tao

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