Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers

P. Vineis, F. Veglia, S. Garte, C. Malaveille, G. Matullo, A. Dunning, M. Peluso, L. Airoldi, K. Overvad, O. Raaschou-Nielsen, F. Clavel-Chapelon, J. P. Linseisen, R. Kaaks, H. Boeing, A. Trichopoulou, D. Palli, P. Crosignani, R. Tumino, S. Panico, H. B. Bueno-De-MesquitaP. H. Peeters, E. Lund, C. A. Gonzalez, C. Martinez, M. Dorronsoro, A. Barricarte, C. Navarro, J. R. Quiros, G. Berglund, B. Jarvholm, N. E. Day, T. J. Key, R. Saracci, E. Riboli, H. Autrup

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1230-1242
Number of pages13
JournalAnnals of Oncology
Volume18
Issue number7
DOIs
Publication statusPublished - Jul 2007

Keywords

  • Bladder cancer
  • Leukemia
  • Lung cancer
  • Metabolic genes
  • Nonsmokers

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Vineis, P., Veglia, F., Garte, S., Malaveille, C., Matullo, G., Dunning, A., Peluso, M., Airoldi, L., Overvad, K., Raaschou-Nielsen, O., Clavel-Chapelon, F., Linseisen, J. P., Kaaks, R., Boeing, H., Trichopoulou, A., Palli, D., Crosignani, P., Tumino, R., Panico, S., ... Autrup, H. (2007). Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers. Annals of Oncology, 18(7), 1230-1242. https://doi.org/10.1093/annonc/mdm109