Format

Send to

Choose Destination
Int J Cancer. 2018 Feb 1;142(3):540-546. doi: 10.1002/ijc.31076. Epub 2017 Oct 12.

Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci.

Author information

1
Department of Medical and Clinical Genetics, Medicum, University of Helsinki, Helsinki, Finland.
2
Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
3
HUNT Research Centre, Department of Public Health, Norwegian University of Science and Technology (NTNU), Levanger, Norway.
4
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
5
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
6
Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
7
Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
8
Estonian Genome Center, University of Tartu, Tartu, Estonia.
9
National Institute for Health and Welfare, Helsinki, Finland.
10
Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.
11
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
12
Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Helsinki, Finland.
13
Faculty of Social Sciences, University of Tampere, Tampere, Finland.
14
National Institute for Health & Welfare, Helsinki, Finland.
15
Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA.
16
Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA.
17
Department of Neurology, Massachusetts General Hospital, Boston, MA.
18
Department of Surgery, Abdominal Center, Helsinki University Hospital, Helsinki, Finland.
19
Department of Pathology, Central Finland Central Hospital, Jyväskylä, Finland.
20
Department of Surgery, Jyväskylä Central Hospital, University of Eastern Finland, Jyväskylä, Finland.
21
Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
22
Wellcome Trust Centre for Human Genetics and NIHR Comprehensive Biomedical Research Centre, Oxford, United Kingdom.
23
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
24
Colon Cancer Genetics Group, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom.
25
The Roslin Institute, University of Edinburgh, Easter Bush, Roslin, United Kingdom.
26
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.
27
Division of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, United Kingdom.
28
CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, United Kingdom.
29
MRC Clinical Trials Unit, , Aviation House, London, United Kingdom.
30
Oxford Cancer Centre, Department of Oncology, University of Oxford, Churchill Hospital, Oxford, United Kingdom.
31
Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom.
32
Colorectal Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Melbourne, VIC, Australia.
33
Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, VIC, Australia.
34
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA.
35
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
36
Department of Preventive Medicine, University of Southern California, Los Angeles, CA.
37
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH.
38
Center for Public Health Genomics, University of Virginia, Charlottesville, VA.

Abstract

Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p = 2.08 × 10-4 ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p = 1.50 × 10-9 ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate < 0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.

KEYWORDS:

colorectal cancer; genetic predisposition to disease; genome-wide association study; single-nucleotide polymorphism

PMID:
28960316
PMCID:
PMC6383773
DOI:
10.1002/ijc.31076
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center