Carcinogenesis Advance Access originally published online on October 19, 2006
Carcinogenesis 2007 28(3):691-697; doi:10.1093/carcin/bgl199
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Cigarette smoke-induced differential gene expression in blood cells from monozygotic twin pairs
1 Department of Health Risk Analysis and Toxicology, Maastricht University PO Box 616, 6200 MD Maastricht, The Netherlands
2 Department of Population Genetics, Genomics and Bioinformatics Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
*To whom correspondence should be addressed. Tel: +31 43 3881092; Fax: +31 43 3884146; Email: J.vanDelft{at}GRAT.unimaas.nl
Chemical carcinogenesis induced by lifestyle factors like cigarette smoking is a major research area in molecular epidemiology. Gene expression analysis of large numbers of genes simultaneously using microarrays holds the opportunity to study the effects of such an exposure at the genome level yielding more mechanism-based information. Therefore, the aim of our study was to investigate multiple gene expressions in blood, indicative for the effects caused by cigarette smoke. Smoking-discordant monozygotic twin pairs (n = 9) were studied to diminish influences of genetic background. Using a dedicated microarray containing 600 toxicologically relevant genes, we investigated which genes are differentially expressed in smokers compared to non-smokers. We also looked for genes of which the expression changes correlated with DNA adducts, a biomarker of effective dose for exposure to cigarette smoke carcinogens. The mean DNA adduct level in smokers differed significantly from that in non-smokers (mean ± standard error 1.96 ± 0.24 versus 1.17 ± 0.16 adducts per 108 nucleotides, respectively; P = 0.04). The genes of which the expression differed most significantly between smokers and non-smokers are ATF4, MAPK14, SOD2, CYP1B1 and SERPINB2. CYP1B1 and SOD2 can directly be linked to cigarette smoke exposure, whereas the other genes are associated with stress or environmentally induced response. Main functions of the genes influenced by cigarette smoking comprise carcinogen metabolism, oxidative stress response and anti-apoptosis.
Abbreviations: EDTA, ethylenediamine tetraacetic acid; PBMC, peripheral blood mononuclear cells
Received July 26, 2006; revised September 27, 2006; accepted October 7, 2006.
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