Mutagenesis Advance Access published online on November 25, 2008
Mutagenesis, doi:10.1093/mutage/gen061
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Environmental exposure measurement in cancer epidemiology
Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, Leeds Institute of Genetics, Health and Therapeutics, LIGHT Laboratories, University of Leeds, Clarendon Way, Leeds LS2 9JT, UK
Environmental exposures, used in the broadest sense of lifestyle, infections, radiation, natural and man-made chemicals and occupation, are a major cause of human cancer. However, the precise contribution of specific risk factors and their interaction, both with each other and with genotype, continues to be difficult to elucidate. This is partially due to limitations in accurately measuring exposure with the subsequent risk of misclassification. One of the primary challenges of molecular cancer epidemiology therefore is to improve exposure assessment. Progress has been made with biomarkers such as carcinogens and their metabolites, DNA and protein adducts and mutations measured in various tissues and body fluids. Nevertheless, much remains to be accomplished in order to establish aetiology and provide the evidence base for public health decisions. This review considers some of the principles behind the application of exposure biomarkers in cancer epidemiology. It also demonstrates how the same biomarkers can contribute both to establishing the biological plausibility of associations between exposure and disease and be valuable endpoints in intervention studies. The potential of new technologies such as transcriptomics, proteomics and metabonomics to provide a step change in environmental exposure assessment is discussed. An increasing recognition of the role of epigenetic changes in carcinogenesis presents a fresh challenge as alterations in DNA methylation, histone modification and microRNA in response to environmental exposures demand a new generation of exposure biomarker. The overall importance of this area of research is brought into sharp relief by the large prospective cohort studies (e.g. UK Biobank) which need accurate exposure measurement in order to shed light on the complex gene:environment interactions underlying common chronic disorders including cancer. It is suggested that a concerted effort is now required, with appropriate funding, to develop and validate the required exposure assessment methodology before these cohorts come to maturity.
To whom correspondence should be addressed. Tel: +44 113 3436601; Fax: +44 113 3436603; Email: c.p.wild{at}leeds.ac.uk
Received on September 9, 2008; revised on October 2, 2008; accepted on October 2, 2008.