title: Development of lung cancer before the age of 50: the role of xenobiotic metabolizing genes.
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.
authors.affiliation: Genetics, Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
authors.forename: Neonilia
authors.initials: N
authors.lastname: Szeszenia-Dabrowska
authors.forename: David
authors.initials: D
authors.lastname: Zaridze
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lissowska
authors.forename: Peter
authors.initials: P
authors.lastname: Rudnai
authors.forename: Eleonora
authors.initials: E
authors.lastname: Fabianova
authors.forename: Dana
authors.initials: D
authors.lastname: Mates
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Janout
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bencko
authors.forename: Valérie
authors.initials: V
authors.lastname: Gaborieau
authors.forename: Lydie
authors.initials: L
authors.lastname: Gioia-Patricola
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bellini
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Janet
authors.initials: J
authors.lastname: Hall
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Rayjean J
authors.initials: RJ
authors.lastname: Hung
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
mesh_terms: D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D050216:Metabolic Detoxication, Phase I / Q000235:genetics*; D050217:Metabolic Detoxication, Phase II / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D015262:Xenobiotics