MTC 04-01Epigenetics and Cancer Risk

12. Molecular markers
M. Widschwendter 1, L. Bjorge 2, I. Bolt 3, D. Cibula 4, N. Colombo 5, I.D. De Beaufort 3, J. Dillner 6, F. Dudbridge 7, I. Evans 1, N. Harbeck 8, A. Jones 1, N. Pashayan 9, F.G. Rebitschek 10, D. Reisel 1, F. Ripp 11, U. Siebert 12, G. Sroczynski 12, E. Steyerberg 13, K. Sundstrom 14, A.E. Teschendorff 1, Y. Vergouwe 13, B. Wahl 11, O. Wegwarth 10, M. Zikan 4.
1Department of Women’s Cancer, Institute for Women’s Health, University College London, London (United Kingdom), 2Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen and CCBIO, Department of Clinical Science, University of Bergen, Bergen (Norway), 3Department of Medical Ethics and Philosophy of Medicine, Erasmus Medical Center, Rotterdam (Netherlands), 4Department of Gynaecological Oncology, Charles University, Prague (Czech Republic), 5European Institute of Oncology, University Milan, Milan (Italy), 6Department of Laboratory Medicine, Karolinska Institutet and the Karolinska University Laboratory, Karolinska University Hospital, Stockholm (Sweden), 7Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London (United Kingdom), 8Breast Center, Department of Gynaecology and Obstetrics, Ludwig-Maximilians Universität, Munich (Germany), 9Department of Applied Health Research, Institute of Epidemiology and Healthcare, University College London, London (United Kingdom), 10Max Planck Institute for Human Development, Harding Center for Risk Literacy, Berlin (Germany), 11GATC Biotech, Konstanz (Germany), 12Institute of Public Health, Medical Decision Making and Health Technology Assessment, Department of Public Health, Health Services Research and HTA, UMIT-University for Health Sciences, Medical Informatics and Technology, Hall in Tirol (Austria), 13Center for Medical Decision Sciences, Department of Public Health, Erasmus MC, Rotterdam (Netherlands), 14Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden (Sweden)

Background / Objectives

While prevention of most female specific cancers (ovarian, breast, endometrial) has not progressed substantially in recent years, significant progress has been made with cervical cancer due to the accessibility of the cell of origin (cervical smear) and availability of a test for a causal agent (human papilloma virus); together these enable identification of high risk individuals and interventions in order to prevent infection or halt the progression to invasive cancer.

Our FORECEE (Female cancer prediction using cervical omics to individualise screening and prevention) consortium has developed an exciting opportunity to utilise clinically abundant cervical cells in tandem with a multi-omics enabled (genome, epigenome, metagenome) analysis pipeline to understand an individual's risk of developing all female specific cancers and to direct a personalised screening and prevention strategy. Cervical cells — currently collected within cervical cancer screening — provide an ideal window into other female specific cancers because they are (i) an excellent non-invasive source of high quality DNA, (ii) provide a readout for environmental exposure, (iii) are part of the Muellerian tract and (iv) are hormone sensitive, recording (via the epigenome) various hormonal conditions over a lifetime that trigger cancer development. 


Methods

Our consortium comprises a multi¬disciplinary team of experts in clinical oncology, risk-benefit communication, omics technologies, decision analysis, health economics and public health. We will examine the effectiveness of the proposed cervical cell omics analysis method and investigate the legal, social, ethical and behavioural issues related to the implementation of the risk prediction tool, through direct interaction with stakeholder groups with a view to ensuring its rapid translation into clinical practice across Europe.


Results

Conclusion

The FORECEE project is aligned with the novel concept of "P4 Medicine" (predictive, preventive, personalised, and participatory): it aims to develop a risk prediction tool and translate its output into personalised recommendations for screening and prevention of female cancers.


References