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Hum Mol Genet. 2014 Sep 1;23(17):4729-37. doi: 10.1093/hmg/ddu177. Epub 2014 Apr 15.

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

Author information

1
Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
2
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.
3
Wellcome Trust Centre for Human Genetics, Oxford, UK.
4
The Roslin Institute, University of Edinburgh, Easter Bush, Roslin EH25 9RG, UK.
5
Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK.
6
Cancer and Population Studies Group, Queensland Institute of Medical Research, Queensland, Australia.
7
Centre for Molecular, Environmental, Genetic and Analytic Epidemiology, The University of Melbourne, Victoria, Australia.
8
Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, USA.
9
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
10
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
11
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
12
Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
13
Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG, UK.
14
Molecular and Population Genetics, Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK richard.houlston@icr.ac.uk iant@well.ox.ac.uk malcolm.dunlop@igmm.ed.ac.uk.
15
The Roslin Institute, University of Edinburgh, Easter Bush, Roslin EH25 9RG, UK richard.houlston@icr.ac.uk iant@well.ox.ac.uk malcolm.dunlop@igmm.ed.ac.uk.
16
Colon Cancer Genetics Group, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK richard.houlston@icr.ac.uk iant@well.ox.ac.uk malcolm.dunlop@igmm.ed.ac.uk.

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 genome-wide 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 × 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.

PMID:
24737748
PMCID:
PMC4133584
DOI:
10.1093/hmg/ddu177
[Indexed for MEDLINE]
Free PMC Article

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