• Assessment of cumulative evidence on genetic associations: interim guidelines.

      Ioannidis, John P.A; Boffetta, Paolo; Little, Julian; O'Brien, Thomas R.; Uitterlinden, Andre G.; Vineis, Paolo; Balding, David J.; Chokkalingam, Anand; Dolan, Siobhan M.; Flanders, W Dana; et al. (Oxford University Press, 2008-02)
      Established guidelines for causal inference in epidemiological studies may be inappropriate for genetic associations. A consensus process was used to develop guidance criteria for assessing cumulative epidemiologic evidence in genetic associations. A proposed semi-quantitative index assigns three levels for the amount of evidence, extent of replication, and protection from bias, and also generates a composite assessment of 'strong', 'moderate' or 'weak' epidemiological credibility. In addition, we discuss how additional input and guidance can be derived from biological data. Future empirical research and consensus development are needed to develop an integrated model for combining epidemiological and biological evidence in the rapidly evolving field of investigation of genetic factors.
    • ECNIS-sponsored workshop on biomarkers of exposure and cancer risk: DNA damage and DNA adduct detection and 6th GUM-32P-postlabelling workshop, German Cancer Research Center, Heidelberg, Germany, 29-30 September 2006.

      Arlt, Volker M.; Frei, Eva; Schmeiser, Heinz H. (Oxford University Press, 2007-01)
      Of all the chemicals classified as carcinogenic to humans by the International Agency for Research on Cancer (IARC), 90% exert their biological effects through binding of their metabolically activated intermediates to DNA forming covalent DNA adducts. As a consequence DNA adducts are generally considered to be causative and directly related to tumour formation. DNA adduct analyses reflect tissue-specific rates of adduct formation and removal, which depend on carcinogen uptake, metabolic activation, DNA repair, adduct instability and tissue turnover and are thus useful markers of carcinogen exposure. The measurement of carcinogen-DNA adduct levels is central to the understanding of chemical carcinogenesis both in animals and humans to determine molecular mechanisms and exposure. Sensitive methods for DNA adduct analysis used to date are based on (32)P-post-labelling, immunoassay, mass spectrometry and laser-induced fluorescence. The aim of this workshop held over 2 days (29-30 September 2006) at the German Cancer Research Center (DKFZ) in Heidelberg, Germany, was to discuss methodological improvements of DNA adduct detection with emphasis on the (32)P-post-labelling procedure as well as new findings achieved by applying the methods to studies on understanding human cancer mechanisms and to elucidate the relationship between adduct formation and human cancer risk.