Biomarkers of ambient air pollution and lung cancer: a systematic review
- Christiana A Demetriou1,2,
- Ole Raaschou-Nielsen3,
- Steffen Loft4,
- Peter Møller4,
- Roel Vermeulen5,
- Domenico Palli6,
- Marc Chadeau-Hyam1,
- Wei W Xun1,
- Paolo Vineis1
- 1Department of Epidemiology and Biostatistics, Imperial College London, London, UK
- 2Department of Electron Microscopy and Molecular Pathology, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus
- 3Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark
- 4Section of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark
- 5Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands
- 6Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, Florence, Italy
- Correspondence to Christiana A Demetriou Department of Electron Microscopy and Molecular Pathology The Cyprus Institute of Neurology and Genetics PO Box. 23462, 1683 Nicosia Cyprus;
Contributors CAD wrote most sections of the manuscript, reviewed the whole document and is a guarantor; SL wrote the section on oxidative damage, contributed figures, and revised the manuscript critically for intellectual content; PM wrote the section on oxidative damage, contributed figures and revised the manuscript critically for intellectual content; OR-N, RV and MC-H presented ideas, provided critical comments on the conclusions and revised the manuscript critically for intellectual content; WX helped produce the funnel plots and revised the manuscript; PD revised the manuscript critically for intellectual content; and PV made a substantial contribution to the conception and design, and analysis and interpretation of data, revised the entire manuscript and is a guarantor.
- Accepted 10 March 2012
- Published Online First 7 July 2012
The association between ambient air pollution exposure and lung cancer risk has been investigated in prospective studies and the results are generally consistent, indicating that long-term exposure to air pollution may cause lung cancer. Despite the prospective nature and consistent findings of these studies, causality assessment can benefit from biomarker research. In the present systematic review, we assess the contribution of intermediate biomarkers in epidemiological studies, to ascertain whether their measurement reinforces causal reasoning. We have reviewed 524 papers which described the relationships between ambient air pollution and biological markers of dose and early response. The evidence for each marker was evaluated using assessment criteria which rate a group of studies from A (strong) to C (weak) on amount of evidence, replication of findings, and protection from bias. Biomarkers that scored A or B for all three criteria are included here. The markers that fulfilled the inclusion criteria are: 1-hydroxypyrene, DNA adducts, chromosomal aberrations, micronuclei, oxidative damage to nucleobases, and methylation changes. These biomarkers cover the whole spectrum of disease onset and progression from external exposure to tumour formation and some have also been suggested as risk predictors of future cancer, reinforcing causal reasoning. However, methodological issues such as confounding, publication bias and use of surrogate tissues instead of target tissues in studies on these markers are of concern. The identified biological markers have potential to shed light on the pathways of carcinogenesis, thus defining the association more clearly for public health interventions.
- air pollution
- lung cancer
- DNA adducts
- chromosomal aberrations
- DNA methylation
- public health
- air pollution
- free radicals
- hygiene/occupational hygiene
- biological monitoring
- retrospective exposure assessment
- longitudinal studies
- exposure assessment
- dermal exposure
- diesel fumes
- contact dermatitis
- mutation research
- P450 cytochrome enzymes
Additional materials are published online only. To view these files please visit the journal online (http://oem.bmj.com).
Funding This work has been made possible by an EU grant to Dr Bert Brunekreef as part of the ESCAPE (European Study of Cohorts for Air Pollution Effects) project and TRANSPHORM, EU FP7 Grant agreement no. 243406 (start date: 1 June 2008, end date: 31 May 2011; MRC-HPA Centre for Environment and Health, Imperial College London).
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.