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Sci Rep. 2015 Dec 1;5:17369. doi: 10.1038/srep17369.

Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1.

Author information

1
Molecular and Population Genetics Laboratory, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
2
Centre for Cancer Genetic Epidemiology, Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.
3
The Molecular Cancer Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
4
Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Victoria, Australia.
5
Centre for Epidemiology and Biostatistics, The University of Melbourne, Victoria, Australia.
6
Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, USA.
7
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
8
Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
9
Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
10
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
11
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
12
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
13
London School of Hygiene and Tropical Medicine, London, UK.
14
Sheffield Cancer Research Centre, Department of Oncology, University of Sheffield, Sheffield, UK.
15
Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, UK and 17 Division of Breast Cancer Research, Institute of Cancer Research, London, UK.
16
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
17
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
18
Department of Oncology, KU Leuven, Belgium.
19
University of California at Los Angeles, Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, Los Angeles, CA, USA.
20
Department of Gynecology and Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
21
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
22
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart, University of Tuebingen, Germany.
23
Department of Clinical Science, Center for Cancer Biomarkers, University of Bergen, Norway.
24
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo, Norway; The K.G. Jebsen Center for Breast Cancer Research, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Clinical Molecular Oncology, Division of Medicine, Akershus University Hospital, Ahus, Norway.
25
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
26
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
27
Grupo de investigación Citogenética, Filogenia y Evolución de Poblaciones, Universidad del Tolima, Ibagué, Tolima, Colombia.
28
Departamento de Antropologia Biologica, Facultad de Humanidades, UDELAR, Magallanes 1577, CP 11200, Montevideo, Uruguay.
29
Universidade de Santiago de Compostel, R/ San Francisco s/n 15782, Santiago de Compostela, Spain.
30
Genetic Predisposition to Colorectal Cancer Group, Gastrointestinal &Pancreatic Oncology Team, IDIBAPS/CIBERehd/Hospital Clínic, Centre Esther Koplowitz (CEK), Rosselló 153 planta 4, 08036 Barcelona, Spain.
31
Universidad Autónoma De Nuevo León, Pedro de Alba s/n, San Nicolás de Los Garza, Nuevo León, Mexico.
32
Hospital A.C. Camargo, São Paulo, Brazil.
33
Department of Genetics and IPO-Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO-Porto), Porto, Portugal, and Biomedical Sciences Institute (ICBAS), University of Porto, Porto, Portugal.
34
School of Medicine and Public Health, University of Newcastle, NSW, Australia.
35
Hunter Medical Research Institute, John Hunter Hospital, Newcastle, NSW, Australia.
36
Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, NSW, Australia.
37
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Mayo Clinic, Rochester, MN, USA.
38
Department of Biostatistics, University of Kansas Medical Center, Kansas City, KS, USA.
39
Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Norway.
40
Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
41
Department of Gynaecology, Jena University Hospital - Friedrich Schiller University, Jena, Germany.
42
Hannover Medical School, Clinics of Gynaecology and Obstetrics, Hannover, Germany.
43
Hannover Medical School, Gynaecology Research Unit, Hannover, Germany.
44
Division of Gynaecological Oncology, University Hospital Leuven, Leuven, Belgium.
45
Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
46
Department of Obstetrics and Gynecology, Division of Tumor Genetics, Technical University of Munich, Munich, Germany.
47
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospitals, KU Leuven, University of Leuven, 3000, Belgium.
48
Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O.Box 3354, Riyadh11211, Saudi Arabia.
49
Institute of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.
50
Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey SM2 5NG, UK.
51
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.
52
The Roslin Institute, University of Edinburgh, Easter Bush, Roslin, EH25 9RG, UK.
53
Centre for Population Health Sciences, University of Edinburgh, Edinburgh, EH8 9AG, UK.
54
Stanford Cancer Institute, Lorry Lokey Building/SIM 1, 265 Campus Drive, Ste G2103, Stanford, CA 94305-5456, USA.
55
Department of Cancer Genetics, St. George's University of London, London SW17 0RE, UK.
56
Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, USA.
57
Oxford NIHR Comprehensive Biomedical Research Centre, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.

Abstract

High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10(-9)) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10(-8)), with the alleles showing opposite effects on the risks of the two cancers.

PMID:
26621817
PMCID:
PMC4664893
DOI:
10.1038/srep17369
[Indexed for MEDLINE]
Free PMC Article

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