Prevent

Prevention of cancers, as opposed to treatment once cancers have become established, may help to significantly reduce mortality, improve the quality of life, and reduce the socioeconomic burden of these diseases.

In combination with our other work to predict individual cancer risk and understand cancer development, we are researching cancer prevention. Some risk factors for cancer development have already been established, and – on a population level – it is known that halting these influences can reduce the risk of developing cancers: for example, smoking dramatically increases the risk for certain cancers, and cessation will therefore reduce the risk for these cancer types. However, it is not known how effective preventive measures are on an individual level (i.e., not every individual may have the same beneficial response to preventive measures).

Our work in prevention focuses on identifying effective preventive measures, as well as being able to monitor effectiveness on an individual basis.

BRCA PREV/END

In the BRCA PREV/END project, we assessed ways to reduce the risk for high risk breast cancer in BRCA mutation carriers.

Paradoxically, BRCA mutation carriers are virtually the only group of women who have the opportunity to reduce breast and ovarian cancer risk almost entirely. Currently however, the price women pay for this is very high as it requires both a bilateral mastectomy and bilateral salpingo-oophorectomy relatively early on in adult life. Angelina Jolie’s disclosure had an enormous impact and resulted in a dramatic increase in the number of women who opted for risk-reducing surgery. Based on this evidence, it would not be practicable or ethical to conduct primary prevention trials that use cancer incidence as an endpoint in BRCA carriers; in addition, these trials would not only require an extended time in which to run but also be prohibitively expensive. Hence, this requires the development of entirely new concepts in cancer prevention including assessment of efficacy in the tissue-at-risk or, ideally, in samples that can be obtained by non-invasive means.

In order to establish intermediate surrogate endpoint markers, we intend to test in vitro (BRCA PREVENT Pre-Clinical) and in vivo (BRCA PREVENT Trials) whether:

the progesterone antagonist Mifepristone is able to prevent/reverse those epigenetic alterations which have been shown to be triggered by a combination of cell-autonomous and cell non-autonomous factors,
this allows us to identify those women who may be able to reduce their breast and ovarian cancer risk by individualised treatment with Mifepristone.

HEAP

We lead on Work Package 8 of the Human Exposome Assessment Platform (HEAP) project looking at age-related changes to the epigenome.

Previous work from our group and others has shown that ageing significantly alters the epigenome. Many factors during life can alter age-related methylation, including exposure to hormones, lifestyle, diet, or infections.

Our innovative work looks at how certain lifestyle changes influence age-related epigenetic parameters, as well as other factors of biological ageing.

THIS PROJECT HAS RECEIVED FUNDING FROM THE EUROPEAN UNION’S HORIZON 2020 RESEARCH AND INNOVATION PROGRAMME UNDER GRANT AGREEMENT NO 874662.

Lifestyle Studies

We are running 3 studies that will deliver comprehensive datasets relating to the impact of lifestyle interventions (intermittent fasting, exercise, psychosocial interventions and smoking cessation) on the epigenome and multiple additional biological endpoints.

1. TirolGESUND study: exploring the hypothesis that lifestyle interventions [smoking cessation or intermittent fasting (with and without ketogenic supplementation)] can lead to changes in epigenetic test results.
2. LIFE-Tirol study: investigating whether lifestyle interventions with the aim of disease prevention [intermittent fasting and/or exercise and/or stress reduction, relaxation and resilience training] are acceptable to the population of Tyrol.
3. SUN-Tirol study: investigating whether smoking cessation is acceptable to the population of Tyrol and whether the motivation to remain smoke-free is influenced by access to information about changes in an individual’s epigenetic markers.

Watch videos describing our work on cancer prevention

Epigenetic clocks

Our work to monitor the efficacy of cancer prevention is underpinned by the development of new epigenetic clocks. Our clocks accurately predict chronological age and are tissue-specific. Our WID-relative epithelial age (WID-REA) clock specifically captures ageing of epithelial cells that line our organs. We are now exploring how these clocks change after changes in lifestyle such as diet, intermittent fasting, exercise and wellbeing interventions.

Breast cancer prevention with antiprogestins

In the second video, we describe the potential for individualised breast cancer prevention and risk monitoring using antiprogestins and a novel type of epigenetic test, the WID-Breast29, Our findings may be particularly valuable for individuals at the highest risk, for instance BRCA mutation carriers.