Annals of Oncology Advance Access published online on May 11, 2007
Annals of Oncology, doi:10.1093/annonc/mdm109
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© 2007 European Society for Medical Oncology
Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers
1 Imperial College London, London, UK, and University of Torino, Italy
2 Institute for Scientific Interchange Foundation, Turin, Italy
3 Genetics Research Institute, Milano, Italy
4 International Agency for Research on Cancer, Lyon, France
5 Department of Oncology, University of Cambridge, Cambridge, UK
6 Cancer Risk Factor Branch, Molecular Biology Laboratory, CSPO-Scientific Institute of Tuscany, Florence, Italy
7 Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy
8 Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark, and Department of Epidemiology and Social Medicine, Institute of Public Health, University of Aarhus, Aarhus, Denmark
9 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
10 Institut National de la Santé et de la Recherche Médicale, ERI 20, EA 4045, and Institut Gustave Roussy, Villejuif, France
11 Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany
12 German Institute of Human Nutrition, Potsdam-Rehbücke, Germany
13 Department of Hygiene and Epidemiology, Medical School, University of Athens, Greece
14 Molecular and Nutritional Epidemiology Unit, CSPO-Scientific Institute of Tuscany Region, Florence, Italy
15 Environmental Epidemiology Unit, National Cancer Institute, Milan, Italy
16 Ragusa Cancer Registry, Sicily, Italy
17 Department of Clinical and Experimental Medicine, University Federico II, Naples, Italy
18 Centre of Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands
19 Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
20 Institute of Community Medicine, University of Tromso, Norway
21 Department of Epidemiology, Catalan Institute of Oncology, Consejería de Sanidad y Servicios Sociales, Barcelona, Spain
22 Andalusian School of Public Health, Granada, Spain
23 Department of Public Health of Guipuzkoa, San Sebastian, Spain
24 Public Health Institute, Navarra, Spain
25 Department of Epidemiology, Murcia Health Council, Murcia, Spain
26 Dirección General de Salud Pública, Consejería de Salud y Servicios Sanitarios Asturias, Oviedo, Spain
27 Malmö Diet and Cancer Study, Lund University, Malmö, Sweden
28 Department of Nutritional Research, University of Umeå, Sweden
29 MRC Dunn Human Nutrition Unit, Cambridge, UK
30 Cancer Research UK Epidemiology Unit, University of Oxford, UK
31 IFC-National Research Council, Pisa, Italy
32 Imperial College London, London, UK
33 Department of Epidemiology and Social Medicine (KO) and Environmental and Occupational Medicine (HA), Institude of Public Health, University of Aarhus, Aarhus, Denmark
* Correspondence to: P. Vineis, Department of Epidemiology and Public Health, Norfolk Place, Imperial College London, London W2 1PG, UK. Tel: +44-20-75943372; Fax: +44-20-75943196; E-mail: p.vineis{at}mperial.ac.uk
Background: We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene–environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia).
Patients and methods: The study has been conducted as a nested case–control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase II metabolizing genes and methylenetetrahydrofolate reductase (MTHFR).
Results: The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00–2.56]; CYP1A1 and leukemia (2.22, 1.33–3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27–0.84; homozygotes); MnSOD and leukemia (1.91, 1.08–3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73–37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63–15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.
bladder cancer, leukemia, lung cancer, metabolic genes, nonsmokers
Received for publication September 21, 2006. Revision received February 22, 2007. Accepted for publication February 22, 2007.
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