DNA damage in blood cells in relation to chemotherapy and nutritional status in colorectal cancer patients.

Diet has a crucial role in protection against colorectal cancer (CRC). Intake of wholegrains, non-starchy-vegetables and fruits, and foods containing dietary fibre reduce the risk, while intake of red- and processed meat, alcoholic drinks and adult body fatness increase the risk of CRC. Such a dietary pattern, which protects against development of CRC, is therefore part of the Norwegian food-based dietary guidelines. Much less is known of the role of the post-diagnostic diet on CRC survivors. The CRC-NORDIET (The Norwegian Dietary Guidelines and Colorectal Survival Study) randomized clinical trial test whether a diet intervention based on the Norwegian dietary guidelines, and a diet rich in antioxidants, will reduce comorbidity and increase survival among colorectal patients after surgery. (Neo-)adjuvant chemotherapy has deleterious effects on muscle tissue resulting in reduced skeletal muscle mass, muscle function and cardiorespiratory fitness, indicating a direct negative effect of chemotherapy on muscle cells. Physical activity is associated with the opposite effect and therefore is a potential effective way to counteract the negative effect of chemotherapy induced impairments in skeletal muscle. A sub-study within the Phys-Can (Physical training and Cancer) consortium, aims to investigate if heavy-load resistance training during (neo-)adjuvant chemotherapy counteracts deleterious effects on skeletal muscle in women diagnosed with breast cancer. DNA damages is major primary causes of cancer but also many other diseases. Nutrition and physical activity?s ability to modulate DNA damage and repair adds a new dimension to the link between diet, exercise, and cancer. Comet assay is a simple and sensitive method to detecting DNA damage and repair at the level of individual cells. This innovation project is a collaboration between the biomedical technology company NorGenoTech, University of Oslo (UiO) and University of Agder (UiA). The project will have access to frozen white blood cells from the CRC-NORDIET study, as well as muscle biopsies from breast cancer patients from the Phys-Can study. The aim of the project will be to study the effect of diet and exercise related to DNA damage and repair in cancer patients. In addition, we will also optimize high throughput comet assay for rapid assessment in cancer patients.

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The randomized controlled trial ‘CRC-NORDIET’ is the first study to test whether dietary intervention in colorectal cancer (CRC) patients after surgery can improve disease-free survival. CRC patients are randomly assigned either to a group receiving intensive encouragement to adopt a diet in accordance with the World Cancer Research Fund (WCRF) recommendations, or to a control group receiving standard care. CRC patients are clinically assessed at baseline, 6 months, 1 year and 3 years, and will be monitored for up to 15 years after diagnosis. Peripheral blood mononuclear cells, buffy coats and plasma are stored frozen at -80°C. They will form the material basis for this PhD project. We will test whether postdiagnostic adherence to WCRF recommendations by CRC patients from the CRC-NORDIET trial improves disease-free survival. The comet assay (single cell gel electrophoresis) will be optimized for an automated high throughput sample processing: for each patient, we will have measures of basal DNA breakage, antioxidant resistance and endogenous oxidative damage. In addition, we will obtain data on individual capacity for DNA repair. These biomarkers taken together are reliable indicators of genome (in)stability. Comparing data from samples taken at different time-points will allow us to assess changes at the individual level, while we will also be able to compare data for the intervention group as a whole with data from the control group. This approach will test the hypothesis that post-diagnostic adherence to the modified diet will decrease endogenous DNA damage, increase resistance to exogenous oxidative damage, and boost DNA repair capacity. In addition, it will be possible to examine links between these biomarkers and the various clinical and biochemical markers that will emerge from the regular clinical assessments.