THEO MURPHY (AUSTRALIA) HIGH FLYERS THINK TANK

Preventative health: Science and technology in the prevention and early detection of disease

University of Sydney (Eastern Avenue Complex), Thursday 6 November 2008

GROUP A: Cancer
Rapporteur: Dr Claire Vajdic

Claire Vajdic obtained a PhD in cancer epidemiology from the University of Sydney in 2002. That year she was awarded a NHMRC postdoctoral fellowship, which she undertook at the National Centre in HIV and Clinical Research, University of New South Wales (UNSW). Since 1996 she has examined the risk factors for cancer, including environmental, infectious and immunological determinants. In 2008 she was awarded a NHMRC Career Development Award, and a Cancer Institute NSW Career Development and Support Fellowship.

Claire conducts a program of public health research examining the relationship between immune dysfunction, infection and the development of cancer. This knowledge is important in advancing our understanding of the causes of cancer, and in developing appropriate preventive strategies and health care for populations. She is quantifying the incidence and risk factors for cancer in children and adults with severe, moderate and mild immune deficiency. While her focus is cancer epidemiology, she actively collaborates with clinicians, immunologists, biomolecular scientists, genetic epidemiologists and histopathologists. She uses established scientific methods as well as novel techniques that capitalise on routinely collected medical statistics. Australia is in a strong position internationally to realise the health benefits achievable through the linkage of existing health datasets. Her research has demonstrated the role of the immune system in the prevention of cancer, and provided an evidence base for the long-term management of patients with immune deficiency.

Our breakout session was quite a lively discussion, and I will endeavour to cover the key issues that we discussed.

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High-throughput genomic, proteomic and metabolic assays are becoming increasingly available and accessible and these technologies have direct application in cancer prevention. The biomolecular profiling of individuals has great potential to contribute to our understanding of cancer predisposition, but its predictive value is strengthened when combined with environmental exposure data. The further development of risk algorithms that combine biomolecular, environmental, demographic, and clinical data presents one of the greatest opportunities for scientific and technological advances in cancer prevention.

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The successful development of such risk algorithms is highly dependent upon effective cross-disciplinary collaboration, and the capacity and infrastructure to build large biospecimen repositories, and to link and analyse large and complex datasets.
Future opportunities for acquiring and possibly combining large, well-characterised cohorts include:

• The systematic compilation of residual biospecimens collected in the course of routine, day-to-day medical practice, for research purposes
  • For example, bloods collected during routine health checks, and excess tissue at the time of surgery
  • Possibly, cord blood and newborn heal prick blood
  • Prospective consent to the use of such tissue for research, including future data linkage, would be essential.
• The collection of biospecimens in addition to data on family history, lifestyle and environment from large cohorts recruited specifically for the purpose (e.g. the 45 and Up Study).
• The targeted study of high-risk population subgroups, with biospecimen and other data collection over a life course, or at a minimum at baseline.

Future opportunities for science and technology to assist in this endeavour include improved and cheaper methods for transporting and storing tissue samples and for the assembly and interrogation of the related databases.

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Substantial evidence now supports the view that variations in the expression of the human genome, particularly through DNA methylation and chromatin remodeling, have a role in the development of cancer. These epigenetic events were highlighted in our discussion because they are potentially reversible, and thus amenable to an intervention. The application of expression microarray technology, which allows the expression of all or most of the genes in the human genome to be analysed simultaneously, has dramatically enhanced the discovery of cancer biomarkers. The recent discovery of the role of small RNAs in governing the epigenetic status of individual genes offers exciting new possibilities in identifying targets for chemoprevention.

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Future opportunities also exist in the application of innovative technology for improving the prospective measurement of an individual's actual cumulative exposure to established cancer risk factors, for example:

• diet (eg capitalising on the widespread availability of mobile telephones and digital cameras to record meals);
• physical activity; and
• sunlight.

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Other promising applications of biomolecular science and technology for cancer prevention include its use in screening and the detection of early, pre­cancerous lesions and other intermediate endpoints. This could enable the targeted management of screen-detected lesions, for example, the identification of lesions that are not clinically relevant and do not require intervention. The biospecimen for such assays would ideally be non- or minimally invasive, for example, a mouth swab or blood sample. The assay might enhance or replace a currently available screening test. All the usual requirements of a screening test must apply, including sensitivity and specificity, cost-effectiveness, and the availability of an effective treatment for the screen-detected lesion or biomarker.

Biological markers also have utility for secondary cancer prevention, such as the classification of the molecular signature of early-stage cancers with respect to their future clinical behavior; for example, one area of need is determining whether some screen-detected cancers behave differently to clinically-presenting cancers. This would enable targeted patient management. The potential for future benefit is vast, particularly for screen-detected breast and prostate cancer. This line of enquiry is a natural extension of the personalised medicine approach that is currently having some success in optimising chemotherapy regimens for cancer patients.

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Prophylactic vaccine development is an area of enormous potential. Over the past 25 years the proportion of all cancers thought to be infection-related has increased from around 5 per cent to close to 20 per cent. The human papillomavirus (HPV) vaccines developed for the prevention of cervical cancer are likely to also reduce the incidence of anal, other anogenital, and oral cancers causally associated with the high-risk HPV types. The development of vaccines against infection with hepatitis C virus, Epstein-Barr virus, and human herpes virus 8 offer great potential for cancer protection globally.

Chemoprevention is the use of agents, both synthetic and naturally occurring such as drugs, vitamins, diet, hormone therapy and other agents, to reduce the risk of cancer. For example, non-steroidal anti-inflammatory drugs are being studied alone and in combination with other agents to see if they reduce the risk of colon cancer for people with a family history of colon polyps or cancer. Selective oestrogen receptor modulators, pharmaceutical agents that block oestrogen's ability to stimulate breast tumour growth, have been shown to reduce the relative risk of breast cancer in high risk women. However, these agents increase the risk for thromboembolic events and endometrial cancer and they have symptomatic side effects. On the basis of consistent epidemiological evidence showing the protective properties of vegetables and fruits, they would appear to offer some of the most promising chemoprevention compounds. There is strong current interest also in the potential chemopreventive properties of green tea.

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Lifestyle and related avenues with potential for the uptake of scientific and technological advances for cancer prevention include:

• strategies to reduce socioeconomic disadvantage;
• compulsory cancer prevention education in schools and broad investment in education at every level;
• the minimisation of carcinogens in the environment;
• the active promotion of 'cancer smart communities', including mandated minimum standards for urban planning and workplace environments, to facilitate healthy lifestyle choices;
• workplace screening and health promotion, possibly with tax incentives for industry;
• complimentary screening and health promotion strategies for those not in the workforce and other disadvantaged and marginalised groups; and
• financial incentives for individuals to reduce their cancer risk profile, for example, listing nicotine replacement therapy on the Pharmaceutical Benefits Scheme.

Finally, there was a plea for funding preventative strategies with a strong evidence base and for implementing them in an equitable way.

Discussion

Question: Christian Gericke, University of Adelaide. I'm not from group A, but I have an additional comment about your last sentence, about doing the things that we have good evidence to do. In theory, I am very much for the evidence-based policy approach. The problem in this field is that there are many things we should do, like food legislation banning advertising of junk food et cetera, where we don't have very good (but not 'level A') evidence such as for individual based approaches. However, we should still do them and gather the evidence at the same time.

Chair: You are suggesting that we should act without evidence?

Christian Gericke: If there is no evidence, yes.