title: DNA repair and cell cycle control genes and the risk of young-onset lung cancer.
abstract: Exposure to tobacco smoke and to mutagenic xenobiotics can cause various types of DNA damage in lung cells, which, if not corrected by DNA repair systems, may lead to deregulation of the cell cycle and, ultimately, to cancer. Genetic variation could thus be an important factor in determining susceptibility to tobacco-induced lung cancer with genetic susceptibility playing a larger role in young-onset cases compared with that in the general population. We have therefore studied 102 single-nucleotide polymorphisms (SNP) in 34 key DNA repair and cell cycle control genes in 299 lung cancer cases diagnosed before the age of 50 years and 317 controls from six countries of Central and Eastern Europe. We have found no association of lung cancer risk with polymorphisms in genes related to cell cycle control, single-strand/double-strand break repair, or base excision repair. Significant associations (P < 0.05) were found with polymorphisms in genes involved in DNA damage sensing (ATM) and, interestingly, in four genes encoding proteins involved in mismatch repair (LIG1, LIG3, MLH1, and MSH6). The strongest associations were observed with heterozygote carriers of LIG1 -7C>T [odds ratio (OR), 1.73; 95% confidence interval (95% CI), 1.13-2.64] and homozygote carriers of LIG3 rs1052536 (OR, 2.05; 95% CI, 1.25-3.38). Consideration of the relatively large number of markers assessed diminishes the significance of these findings; thus, these SNPs should be considered promising candidates for further investigation in other independent populations.
authors.affiliation: Dip. Biologia-Genetics, University of Pisa, Pisa, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
authors.forename: Federica
authors.initials: F
authors.lastname: Gemignani
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Valérie
authors.initials: V
authors.lastname: Gaborieau
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.forename: Debora
authors.initials: D
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: Lydie
authors.initials: L
authors.lastname: Gioia-Patricola
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; D000367:Age Factors; D016022:Case-Control Studies; D004260:DNA Repair; D005061:Europe, Eastern / Q000453:epidemiology; D005260:Female; D018816:Genes, cdc; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged