1. Development of lung cancer before the age of 50: the role of xenobiotic metabolizing genes
- Author
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Ilaria Bellini, Lenka Foretova, Stefano Landi, Jolanta Lissowska, Federica Gemignani, Vladimir Bencko, Valerie Gaborieau, David Zaridze, Rayjean J. Hung, Janet Hall, Dana Mates, Neonilia Szeszenia-Dabrowska, Federico Canzian, Peter Rudnai, Roberto Barale, Vladimir Janout, Paul Brennan, Lydie Gioia-Patricola, Eleonora Fabianova, Paolo Boffetta, Gemignani, F., Landi, S., Szeszenia-Dabrowska, N., Zaridze, D., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Foretova, L., Janout, V., Bencko, V., Gaborieau, V., Gioia-Patricola, L., Bellini, I., Barale, R., Canzian, F., Hall, J., Boffetta, P., Hung, R.J., and Brennan, P.
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Adult ,Male ,Cancer Research ,Lung Neoplasms ,Development lung cancer before age of 50 role xenobiotic metabolizing gene ,Single-nucleotide polymorphism ,EPHX1 ,Biology ,medicine.disease_cause ,Polymorphism, Single Nucleotide ,Xenobiotics ,medicine ,Humans ,Age of Onset ,Lung cancer ,CYP2A6 ,Oligonucleotide Array Sequence Analysis ,Genetics ,Haplotype ,Heterozygote advantage ,General Medicine ,Middle Aged ,medicine.disease ,Metabolic Detoxication, Phase II ,Phenotype ,Haplotypes ,Case-Control Studies ,Methylenetetrahydrofolate reductase ,biology.protein ,Female ,Metabolic Detoxication, Phase I ,Carcinogenesis - Abstract
The role of genes coding for xenobiotic metabolizing enzymes (XMEs) and the risk of lung cancer is unclear. Under the assumption that these genes may be more important among people having a diagnosis of lung cancer at younger ages, we have investigated the role of single-nucleotide polymorphisms (SNPs) within phase I and phase II XME genes, and also genes involved in the metabolism of nucleic acids in a series of young onset patients and matched controls. We genotyped 299 lung cancer cases diagnosed before the age of 50 and 317 controls, from six countries of Central and Eastern Europe, by use of an oligonucleotide microarray and arrayed primer extension technique for 45 SNPs in 15 phase I XME genes, 46 SNPs in 17 phase II genes and 9 SNPs in 4 genes related to metabolism of nucleic acids. Heterozygote carriers of SNPs in CYP1A2 1545T>C, -164C>A and -740T>G; CYP2A6 -47A>C; MDR1 3435T>C; NAT1 1088T>A and 1095A>C; GSTA2 S112T; GSTM3 V224I and MTHFR A222V had altered risk of developing lung cancer. Phenotypes reconstructed after haplotype analyses showed that the carriers of the combined NAT1 fast+ NAT2 fast phenotypes were at lower risk when compared with those with the combined NAT1 slow + NAT2 slow acetylator phenotypes. Finally, extensive EPHX1 metabolizers showed an increased risk as compared with the poor metabolizers. © The Author 2007. Published by Oxford University Press. All rights reserved.
- Published
- 2007
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