Genetic susceptibility according to three metabolic pathways in cancers of the lung and bladder and in myeloid leukemias in nonsmokers
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 JP., Kaaks R., Boeing H., Trichopoulou A., Palli D., Crosignani P., Tumino R., Panico S., Bueno-De-Mesquita HB., Peeters PH., Lund E., Gonzalez CA., Martinez C., Dorronsoro M., Barricarte A., Navarro C., Quiros JR., Berglund G., Jarvholm B., Day NE., Key TJ., Saracci R., Riboli E., Autrup H.
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. © 2007 European Society for Medical Oncology.