TY - JOUR
T1 - Development of lung cancer before the age of 50
T2 - The role of xenobiotic metabolizing genes
AU - Gemignani, Federica
AU - Landi, Stefano
AU - Szeszenia-Dabrowska, Neonilia
AU - Zaridze, David
AU - Lissowska, Jolanta
AU - Rudnai, Peter
AU - Fabianova, Eleonora
AU - Mates, Dana
AU - Foretova, Lenka
AU - Janout, Vladimir
AU - Bencko, Vladimir
AU - Gaborieau, Valérie
AU - Gioia-Patricola, Lydie
AU - Bellini, Ilaria
AU - Barale, Roberto
AU - Canzian, Federico
AU - Hall, Janet
AU - Boffetta, Paolo
AU - Hung, Rayjean J.
AU - Brennan, Paul
PY - 2007/6
Y1 - 2007/6
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/34447301791
U2 - 10.1093/carcin/bgm021
DO - 10.1093/carcin/bgm021
M3 - Article
C2 - 17259654
AN - SCOPUS:34447301791
SN - 0143-3334
VL - 28
SP - 1287
EP - 1293
JO - Carcinogenesis
JF - Carcinogenesis
IS - 6
ER -