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Nat Genet. 2015 Aug;47(8):911-6. doi: 10.1038/ng.3341. Epub 2015 Jun 22.

Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.

Author information

1
Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, Maryland, USA.
2
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
3
1] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [2] Department of Biology, University of Pisa, Pisa, Italy.
4
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA.
5
Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario, Canada.
6
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
7
Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
8
Department of Population Health, QIMR Berghofer Medical Research Institute, Kelvin Grove,Queensland, Australia.
9
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
10
International Agency for Research on Cancer (IARC), Lyon, France.
11
Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, US Department of Health and Human Services, Bethesda, Maryland, USA.
12
Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
13
Laboratory for Experimental Oncology and Radiobiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
14
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany.
15
1] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. [2] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. [3] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [4] Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
16
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
17
Digestive and Liver Disease Unit, 'Sapienza' University of Rome, Rome, Italy.
18
Università Vita Salute San Raffaele and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy.
19
1] Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada. [2] Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
20
1] Cancer Care Ontario, University of Toronto, Toronto, Ontario, Canada. [2] Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
21
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and Medical Faculty Masaryk University, Brno, Czech Republic.
22
1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
23
Department of Surgery, Unit of Experimental Surgical Pathology, University Hospital of Pisa, Pisa, Italy.
24
Department of Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Athens, Greece.
25
Department of Radiation Oncology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
26
Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
27
Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
28
Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
29
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
30
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
31
Department of Biology, Section of Genetics, University of Pisa, Pisa, Italy.
32
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA.
33
Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.
34
Department of Oncology, Azienda USL 1 Massa Carrara, Massa Carrara, Italy.
35
Laboratory of Toxicogenomics, Institute of Public Health, Prague, Czech Republic.
36
National Institute for Health Research (NIHR) Pancreas Biomedical Research Unit, Liverpool Clinical Trials Unit and Cancer Research UK Clinical Trials Unit, Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
37
Department of Surgery, Gastroenterology and Oncology, University of Padua, Padua, Italy.
38
Pancreas Unit, Department of Digestive Diseases, Sant'Orsola-Malpighi Hospital, Bologna, Italy.
39
ARC-NET-Centre for Applied Research on Cancer, University and Hospital Trust of Verona, Verona, Italy.
40
Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, US National Institutes of Health, Rockville, Maryland, USA.
41
Department of General Surgery, University Hospital Heidelberg, Heidelberg, Germany.
42
Division of Gastroenterology and Research Laboratory, IRCCS Scientific Institute and Regional General Hospital 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy.
43
Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
44
Department of Molecular Biology of Cancer, Institute of Experimental Medicine, Academy of Sciences, Prague, Czech Republic.
45
1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
46
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.
47
1] Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA. [2] Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

Abstract

Pancreatic cancer is the fourth leading cause of cancer death in the developed world. Both inherited high-penetrance mutations in BRCA2 (ref. 2), ATM, PALB2 (ref. 4), BRCA1 (ref. 5), STK11 (ref. 6), CDKN2A and mismatch-repair genes and low-penetrance loci are associated with increased risk. To identify new risk loci, we performed a genome-wide association study on 9,925 pancreatic cancer cases and 11,569 controls, including 4,164 newly genotyped cases and 3,792 controls in 9 studies from North America, Central Europe and Australia. We identified three newly associated regions: 17q25.1 (LINC00673, rs11655237, odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.19-1.34, P = 1.42 × 10(-14)), 7p13 (SUGCT, rs17688601, OR = 0.88, 95% CI = 0.84-0.92, P = 1.41 × 10(-8)) and 3q29 (TP63, rs9854771, OR = 0.89, 95% CI = 0.85-0.93, P = 2.35 × 10(-8)). We detected significant association at 2p13.3 (ETAA1, rs1486134, OR = 1.14, 95% CI = 1.09-1.19, P = 3.36 × 10(-9)), a region with previous suggestive evidence in Han Chinese. We replicated previously reported associations at 9q34.2 (ABO), 13q22.1 (KLF5), 5p15.33 (TERT and CLPTM1), 13q12.2 (PDX1), 1q32.1 (NR5A2), 7q32.3 (LINC-PINT), 16q23.1 (BCAR1) and 22q12.1 (ZNRF3). Our study identifies new loci associated with pancreatic cancer risk.

PMID:
26098869
PMCID:
PMC4520746
DOI:
10.1038/ng.3341
[Indexed for MEDLINE]
Free PMC Article

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