Environmental exposure and cancer prevention

Chair: Linda Bauld, University of Stirling, UK
Speaker: John Cherrie, Heriot Watt University, Edinburgh, UK
Speaker: Lion Shahab, University College London, UK
Speaker: Marion MacFarlane, MRC Toxicology Unit, UK

11:00 am-12:30 pm

Room: M2-4

This session will examine environmental exposures that may be relevant to cancer and have so far to date received less attention than other potential risk factors. It will also examine these exposures in contrast to well-established preventable risk factors.

The topics to be covered include: carbon nanotubes; air pollution and alternative nicotine delivery devices (e-cigarettes and heat not burn tobacco).

Use and safety of novel alternative nicotine delivery devices: a role for cancer harm reduction?
Speaker: Lion Shahab
Affiliation: University College London


This presentation will cover latest data from the UK and further afield to evaluate the role that alternative nicotine delivery devices can play in harm reduction. This talk will have a specific focus on e-cigarettes and heat-not-burn devices, their safety, current prevalence of use and impact on smoking cessation.

Air pollution and cancer
Speaker: John Cherrie
Affiliation: Heriot Watt University and the Institute of Occupational Medicine


Air pollution is a risk factor for cancer. Outdoor air pollution is a complex mixture of gases (e.g. NO2, SO2 and O3) and particles (e.g. PM2.5) that arise from a diverse range of sources, including motor vehicles and industrial facilities. An increased risk of lung cancer is consistently seen in epidemiological studies and in animal toxicology and the risk is most clearly associated with exposure to particulate matter. Epidemiological studies have mostly been carried out in Europe and North America where PM2.5 concentrations are typically between around 10 and 30 micro-g/m3; much higher concentrations are seen in emerging economies in Southeast Asia and elsewhere. There is limited evidence that bladder cancer risks are associated with outdoor pollution.  In Europe and North America air pollution levels are steadily decreasing over time as a result of technological developments reducing emissions, but in other parts of the world levels are increasing. There are limited possibilities for reduction in exposure from behavioral interventions. There is uncertainty about the magnitude of the risk and the shape of the exposure-response curve, but a 10 micro-g/m3 in outdoor PM2.5 could result in a reduction in the lung cancer population attributable fraction of between around 3% and 30%

Carbon Nanotubes may pose Asbestos-style Cancer Risk
Speaker: Marion MacFarlane
Affiliation: MRC Toxicology Unit, University of Cambridge


Exposure to asbestos fibres causes pathological changes in the pleural cavity including malignant mesothelioma.  Length-dependent retention of asbestos fibres in the pleural cavity is crucial for disease development.  Chronic inflammation plays a key role in carcinogenesis and epigenetic events, rather than driver mutations, are considered to be major causative factors.  New advanced materials such as carbon nanotubes offer an exciting frontier for innovation but safety is imperative. Prior to understanding the risks posed by exposure to asbestos, it was considered a wonder material with numerous applications yet a tragic legacy arose from its widespread use. Knowledge of the sequence of events from exposure to asbestos to the formation of mesothelioma is vital for identifying any risks posed by new fibres. Certain forms of carbon nanotubes (CNT) are similar to asbestos in terms of their high aspect-ratio and thus may pose an asbestos-like inhalation hazard, however the molecular mechanisms underlying their carcinogenic potential have not been fully explored.

Using a model of direct injection into the pleural cavity, we compared the molecular changes which occur at the mesothelium after exposure to occupationally-relevant concentrations of short/long asbestos fibres and short/long CNT over 20 months. We show a common pro-oncogenic activity of long CNT and long asbestos throughout disease progression. Key molecular events encompass changes in gene expression/signaling pathway activation, oxidative DNA damage, increased mitosis and proliferation.  Instillation of long CNTs into the pleural cavity of mice induces chronic inflammation and pro-oncogenic changes leading to development of mesothelioma, with deletion of p19/Arf and silencing of p16/Ink4a and NF2.  Epigenetic changes induced by pathogenic fibres occur at the pre-neoplastic stage of disease and thus may play a role in progression of pleural inflammatory lesions to malignant mesothelioma.

Our data demonstrate that exposure to long-fibre CNT induces development of pleural mesothelioma, replicating the pathogenesis of human disease and highlighting commonality in the hazard mechanism of long pathogenic fibres at the molecular level. Crucially, our findings reinforce concerns that long-fibre carbon nanotubes (and potentially other high-aspect-ratio fibres) may present the same carcinogenic hazard as asbestos. However, we found that it was only CNTs which were long, thin and bio-persistent (those which aren’t broken down and expelled by the immune system) which posed a hazard. Thus, our findings open up the possibility of more effective/efficient screening of advanced fibres to better identify/mitigate risks and ensure safety.