N2-ethyldeoxyguanosine as a potential biomarker for assessing effects of alcohol consumption on DNA

Silvia Balbo, Mia Hashibe, Sarolta Gundy, Paul Brennan, Cristina Canova, Lorenzo Simonato, Franco Merletti, Lorenzo Richiardi, Antonio Agudo, Xavier Castellsagué, Ariana Znaor, Renato Talamini, Vladimir Bencko, Ivana Holcátová, Mingyao Wang, Stephen S. Hecht, Paolo Boffetta

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41 Citations (Scopus)

Abstract

Head and neck cancers are causally related to alcohol consumption, but the underlying mechanisms are unclear. Ethanol is metabolized to acetaldehyde, an experimental carcinogen. Quantitation of the major DNA adduct of acetaldehyde, N2-ethylidenedeoxyguanosine, in human tissues could help to elucidate the mechanism of alcohol carcinogenicity. We applied a quantitative method for the analysis of this adduct, measured as the NaBH3CN reduction product N2-ethyldeoxyguanosine (N2-ethyl-dGuo) by liquid chromatography-electrospray ionization-tandem mass spectrometry-selected reaction monitoring, on DNA (0.04 ± 0.03 mg) isolated from blood collected from control subjects recruited from two studies conducted in different areas of Europe between 1999 and 2005. The group selected from the first study (n = 127) included alcohol drinkers and abstainers while the group from the second study (n = 50) included only heavy drinkers. N 2-ethyl-dGuo was detected in all DNA samples. After adjusting for potential confounders, in the first study, drinkers showed a higher level of N2-ethyld-Guo (5,270 ± 8,770 fmol/Mmol dGuo) compared with nondrinkers (2,690 ± 3040 fmol/Mmol dGuo; P = 0.04). A significant trend according to dose was observed in both studies (P = 0.02 and 0.04, respectively). Taking into account the amount of alcohol consumption, adduct levels were higher in younger compared with older subjects (P = 0.01), whereas no differences were observed comparing men with women. These results show the feasibility of quantifying N2-ethyl-dGuo in small-volume blood samples and are consistent with the hypothesis that ethanol contributes to carcinogenesis through DNA adducts formation.

Original languageEnglish
Pages (from-to)3026-3032
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 1 2008

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Balbo, S., Hashibe, M., Gundy, S., Brennan, P., Canova, C., Simonato, L., Merletti, F., Richiardi, L., Agudo, A., Castellsagué, X., Znaor, A., Talamini, R., Bencko, V., Holcátová, I., Wang, M., Hecht, S. S., & Boffetta, P. (2008). N2-ethyldeoxyguanosine as a potential biomarker for assessing effects of alcohol consumption on DNA. Cancer Epidemiology Biomarkers and Prevention, 17(11), 3026-3032. https://doi.org/10.1158/1055-9965.EPI-08-0117