DNA repair and cell cycle control genes and the risk of young-onset lung cancer

Stefano Landi, Federica Gemignani, Federico Canzian, Valérie Gaborieau, Roberto Barale, Debora Landi, Neonilia Szeszenia-Dabrowska, David Zaridze, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Lenka Foretova, Vladimir Janout, Vladimir Bencko, Lydie Gioia-Patricola, Janet Hall, Paolo Boffetta, Rayjean J. Hung, Paul Brennan

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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.

Original languageEnglish
Pages (from-to)11062-11069
Number of pages8
JournalCancer Research
Volume66
Issue number22
DOIs
Publication statusPublished - Nov 15 2006

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Landi, S., Gemignani, F., Canzian, F., Gaborieau, V., Barale, R., Landi, D., Szeszenia-Dabrowska, N., Zaridze, D., Lissowska, J., Rudnai, P., Fabianova, E., Mates, D., Foretova, L., Janout, V., Bencko, V., Gioia-Patricola, L., Hall, J., Boffetta, P., Hung, R. J., & Brennan, P. (2006). DNA repair and cell cycle control genes and the risk of young-onset lung cancer. Cancer Research, 66(22), 11062-11069. https://doi.org/10.1158/0008-5472.CAN-06-1039