Combined Impact of Lifestyle, Dietary and Metabolic Factors on Colorectal Cancer Incidence and Survival in European Populations: Implications for Cancer Risk Assessment and Risk Prediction

• Applicant: Professorin Krasimira Aleksandrova, Ph.D.
• Subject Area: Epidemiology and Medical Biometry/Statistics ; Nutritional Sciences
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 271735519

Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide with almost 55% of the cases occurring in developed countries, such as in Western Europe. Development of risk prediction models for CRC in European men and women is urgently needed to enhance its prevention. The parallel of disease frequency with the level of westernization points to the likely involvement of lifestyle and metabolic factors in the etiology of CRC. Mounting evidence, including data from the European Prospective Investigation into Cancer and Nutrition (EPIC) suggests that behavioral factors such as alcohol, smoking, physical activity, body fatness, and certain dietary and metabolic factors are individually related to a higher CRC risk. While individual roles of these factors have been extensively investigated, little is known about their joint effects. However, in real life it is uncommon that people practice isolated behaviors; therefore a multidimensional data analysis approaches would be more informative for exploring disease etiology, as well as for translating epidemiological findings into meaningful public health messages. With this application, we propose to explore the impact of combinations of lifestyle, dietary and metabolic factors on CRC incidence and survival, and to develop practical public health tools for CRC risk assessment and risk prediction. More concretely, we will use a-priori knowledge on CRC risk factors to compose lifestyle and metabolic biomarker indexes and explore associations of these indexes with CRC incidence and survival. As a further step, we will develop a CRC risk prediction model and evaluate the performance of this model in terms of its calibration, discrimination and accuracy. Finally, we will explore whether newly established biomarker and genetic data potentially improves risk prediction beyond known CRC risk factors. Proposed analyses will be embedded within the EPIC cohort comprising of 519,928 men and women, aged 25-70 years, who provided dietary and lifestyle information, anthropometric measurements and blood samples (1992-2000), and were followed up through September 31, 2010. Over a mean follow-up of 12 years, 4,452 incident CRC cases (2,817 colon, and 1,635 rectal) and 1,107 CRC-specific deaths were identified. The project will utilize the unique study setting of the EPIC cohort, and will profit from its strong design, large number of cases and availability of high-quality epidemiological data on variety of risk factors. The risk prediction model developed within this project could be ultimately used for identifying high risk groups and developing intervention strategies for CRC. Therefore, this project brings promises to be of direct impact for the primary prevention of CRC in clinical practice and public health.

• DFG Programme: Research Grants
• International Connection: France, Netherlands, United Kingdom
• Co-Investigators: Wolfgang Bernigau; Professor Dr. Heiner Boeing; Ellen Kohllsdorf; Dr. Annika Steffen
• Cooperation Partners: H. Bas Bueno-de-Mesquita; Dr. Mazda Jenab; Dr. Teresa Norat; Elio Riboli, Ph.D.; Dr. Isabelle Romieu