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Carcinogenesis. 2014 Aug;35(8):1737-44. doi: 10.1093/carcin/bgu064. Epub 2014 Mar 24.

Genome-wide interaction study of smoking and bladder cancer risk.

Author information

1
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA, Institute for Cancer Research, London, UK, Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain, Municipal Institute of Medical Research, Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, National School of Public Health, Athens, Greece, Maine Cancer Registry, Augusta, ME, USA, Spanish National Cancer Research Centre (CNIO), Madrid, Spain, Vermont Cancer Registry, Burlington, VT, USA, Center for Genomics Research, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD, USA, Information Management Services, Inc., Rockville, MD, USA, Imperial College London, London, UK, Department of Preventive Medicine and Department of Obstetrics & Gynecology, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA, Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA, USA, Department of Urology, Assistance Publique-Hôpitaux de Paris, Tenon Hospital, Paris, France, Centre de Recherche sur les Pathologies Prostatiques, Paris, France, Institut national de la sante et de la recherche medicale, U946, Foundation Jean Dausset Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France, Centre National de la Receherche Scientifique, UMR8200, Institut Gustave-Roussy, Villejuif, France, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy, National Institute for Public Health and the Environment (RIVM), Biltho
2
Institute for Cancer Research, London, UK.
3
Epidemiology Research Program, American Cancer Society, Atlanta, GA, USA.
4
Maine Cancer Registry, Augusta, ME, USA.
5
Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
6
Vermont Cancer Registry, Burlington, VT, USA.
7
Center for Genomics Research, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD, USA.
8
Information Management Services, Inc., Rockville, MD, USA.
9
Imperial College London, London, UK.
10
Department of Preventive Medicine and Department of Obstetrics & Gynecology, Keck School of Medicine of USC, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
11
Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA, USA.
12
Department of Urology, Assistance Publique-Hôpitaux de Paris, Tenon Hospital, Paris, France, Centre de Recherche sur les Pathologies Prostatiques, Paris, France.
13
Institut national de la sante et de la recherche medicale, U946, Foundation Jean Dausset Centre d'Etude du Polymorphisme Humain (CEPH), Paris, France, Centre National de la Receherche Scientifique, UMR8200, Institut Gustave-Roussy, Villejuif, France.
14
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
15
Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy.
16
Imperial College London, London, UK, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands, Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands.
17
Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
18
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
19
CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, Public Health Division of Gipuzkoa, BioDonostia Research Institute, Health Department of Basque Region, San Sebastian, Spain.
20
Cancer Epidemiology Unit, University of Oxford, Oxford, UK.
21
Danish Cancer Society Research Center, Copenhagen, Denmark.
22
International Agency for Research on Cancer, Lyon, France.
23
DKFZ, Heidelberg, Germany.
24
Genomic Medicine Group, Galician Foundation of Genomic Medicine, Complejo Hospitalario Universitario de Santiago, Servicio Galego de Saude (SERGAS), Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.
25
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
26
UPMC Univ Paris 06, GRC n°5,ONCOTYPE-URO, Paris, France.
27
Department of Urology, Assistance Publique-Hôpitaux de Paris, Tenon Hospital, Paris, France, Centre de Recherche sur les Pathologies Prostatiques, Paris, France, UPMC Univ Paris 06, GRC n°5,ONCOTYPE-URO, Paris, France.
28
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
29
Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, MA, USA.
30
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
31
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA, Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA.
32
Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Padova, Italy;
33
Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
34
New Hampshire Department of Health and Human Services, Concord, NH, USA and.
35
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.

Abstract

Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10(-) (5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 × 10(-) (7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 × 10(-) (7)). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.

PMID:
24662972
PMCID:
PMC4123644
DOI:
10.1093/carcin/bgu064
[Indexed for MEDLINE]
Free PMC Article

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