The appointment of Cornelia Ulrich as professor and head of the Departments of Preventive Oncology at the National Centre for Tumour Diseases and the German Cancer Research Centre, shows that Heidelberg is expanding its research priorities in the prevention and early diagnosis of cancer.
In September 2009, Professor Cornelia Ulrich returned to Germany from the renowned Fred Hutchinson Cancer Research Centre (FHCRC) in Seattle, USA. She took charge of the new Department of Preventive Oncology at the National Centre for Tumour Diseases (NCT), where she is a member of the NCT board of directors and she also heads up the newly established Department of Preventive Oncology at the German Cancer Research Centre (DKFZ) where she holds an excellence professorship.
After completing her undergraduate nutritional science studies at the University of Hohenheim, Ulrich did her master's degree thesis on nutrition at Oregon State University in Corvallis, USA. She did her PhD in the field of epidemiology at the University of Washington in Seattle, and spent ten years at the FHCRC. As part of her professorship in the cancer prevention programme she investigated how the development and prognosis of cancer depends on each individual's genetic makeup. Ulrich has published more than 150 scientific papers and has made a name for herself through her studies on the molecular epidemiology and pharmacogenetics of colorectal carcinoma. Her main focus has been on the folic acid metablism (C1 compounds) and inflammation.
The establishment of the National Centre for Tumour Diseases (NCT), a collaborative project between the German Cancer Research Centre, the University Hospital in Heidelberg, the Thorax Clinic in Heidelberg and German Cancer Aid, was a milestone for Heidelberg as an international leader in the research and treatment of cancers. The idea behind the NCT concept is to transfer research results as quickly and as effectively as possible to patient treatment, by bringing together applied research and clinical application quite literally under one roof. The researchers will move into the new NCT building on the Heidelberg University Hospital campus later this year.
Professor Ulrich was also in charge of coordinating the interdisciplinary ColoCare study at the FHCRC and is now working to further expand the study in collaboration with international colleagues in Heidelberg (NCT, DKFZ, University Hospital) and the Moffitt Cancer Centre in Tampa, Florida. The objective of the study is to identify factors that determine the survival of colorectal cancer patients. This includes hereditary genetic factors as well as tumour characteristics that have an effect on the early diagnosis and the success of therapy, as well as individual factors such as nutrition and sports that have a beneficial effect on human health. The international ColoCare consortium comprises more than thirty professors at three centres – Heidelberg, Seattle and Tampa. The researchers hope to improve colon cancer treatment by adapting the therapy to the requirements of individual patients in order to improve the success rates of treatment outcome at the same time as reducing potential side effects. The study also hopes to identify what patients themselves can do to improve their prognosis and well-being after being diagnosed with colon cancer.In the Department of Preventive Oncology that Cornelia Ulrich is currently setting up, the scientist is also looking into the influence of genetic factors on the pathogenesis of cancer, cancer prognosis and the interactions caused by nutrition and drugs, amongst other things. The objective of the research is to develop concepts for primary and secondary cancer prevention, i.e. the prevention of cancer and the early diagnosis and therapy of cancer prestages. This requires researchers to carry out epidemiological investigations as well as develop innovative, reliable and mass-suitable screening methods.
Folate or folic acid is a precursor of the coenzyme tetrahydrofolic acid (THF). It is an essential vitamin that needs to be taken up with food. THF supplies C1 compounds (especially methyl and formyl groups) and is involved in a large number of metabolic functions, in particular in the synthesis of DNA building blocks and the amino acid methionine. The uptake of insufficient amounts of folic acid can lead to severe damage, for example neural tube defects in unborn children (spina bifida). Pregnant women who tend to have higher folate requirements therefore consume large quantities. The pharmaceutical industry supplies folate as a supplement in functional food (nutraceuticals). In the USA, Canada and Chile, the addition of folate to flour and cereals has been mandatory for over ten years. Australia, Great Britain and other countries are currently debating the mandatory addition of folate to food.The methyl groups of folate are used for the methylation of DNA, which is an important epigenetic mechanism for silencing genes. Methylation also plays a role in tumour development and progression. Cornelia Ulrich carries out pharmacogenetic and epidemiological studies in cooperation with colleagues at the FHCRC and other institutions, focusing on the differences in the folate metabolism and its relation to cancer risk. Cornelia Urlich explains that folic acid has an ambivalent effect, which is referred to as “Janus head” in the literature. On the one hand, there is evidence that the uptake of larger amounts of folic acid reduces the risk of developing colorectal carcinoma (and potentially also other cancers such as breast cancer, cervical and pancreatic carcinomas). The substance seems to exert its effect on the DNA repair system, thereby preventing the accumulation of mutations and genomic instability. On the other hand, folate seems to promote the growth of tumours in cases where early cancer stages (adenomas, in the case of colon carcinoma adenomatous polyps) are already present. It is clear from this evidence that there is a need to investigate the effect of folate in cancer patients. It is seen as extremely worrying that cancer patients often consume large quantities of folate without the knowledge of their doctors. This often includes vitamin tablets, health drinks and food as well as functional food containing vitamin supplements.
In addition, frequently used chemotherapeutics such as methotrexate and 5-fluoruracil have an effect on the enzymes of the folate metabolism, and there is evidence that their effect and toxicity are associated with genetic polymorphisms in the folate metabolism. Given the numerous areas in which folate can play a role (for example the genetics and constitution of cancer patients, tumour characteristics, chemotherapy and food supplements), Ulrich insists that careful prognostic studies on folate and cancer must be carried out as part of an integrated, interdisciplinary approach. Ulrich believes it is necessary to postpone plans to introduce the addition of folate to food in other countries until detailed insights into the potential effect of folic acid on the growth of cancer are obtained. She is sure that healthy, varied food, in particular a lot of fresh vegetables and fruit, can cover the daily folate requirements of 400 µg without the need to take pills and food supplements.
There is also no scientific evidence available on the potential effects of other vitamins and minerals taken by many people as dietary supplements without medical advice. It is not sure whether such supplements are beneficial or harmful for cancer patients or for people in whom standard cancer treatment has been successful. Ulrich systematically investigated the application of vitamins and minerals in the USA as part of the cancer prevention programme at the FHCRC, where she focused particularly on tumour characteristics and socio-democratic factors in order to identify the most persistent problems in this field and initiate studies with the aim of closing existing gaps of knowledge.
Further research projects in which Cornelia Ulrich is currently involved focus on the preventive effect of non-steroidal anti-inflammatory drugs, NSAIDs, such as aspirin or ibuprofen, for example. These drugs, which inhibit cyclooxygenase enzymes (COX) and hence the synthesis of prostaglandin, help to considerably reduce the risk of developing colon cancer. It would appear that they have the same effect in stomach, breast and lung cancer, although no information is currently available on whether this type of treatment provides protection against the development of cancer or the growth of prestages, i.e. primary or secondary prevention. It is possible that the protection offered by NSAIDs may be negated by potential toxic effects on the cardiovascular system. It is likely that genetic factors (polymorphism) also play a part in the different responses of patients to such drugs. Pharmacogenetic investigations are necessary in order to determine the benefit-risk ratio of NSAIDs and in order to put in place chemopreventive measures tailored to the requirements of individual patients.
Another area of research dealt with by Cornelia Ulrich's department focuses on the influence of sport on primary and tertiary (referring to the improvement in the quality of life and prognosis after a person has developed a cancer) cancer prevention. Numerous investigations suggest that sport and physical activity play an important role in the prevention of cancer as well as in the after-treatment of patients. It is also known that sport has positive effects on rehabilitation. Ulrich points out that lack of physical activity and incorrect nutrition not only cause metabolic disease, but also increase cancer risk. Studies show that women who regularly do physical activity, are less likely to develop breast cancer, while overweight postmenopausal women have a significantly higher risk of developing breast cancer. The development of colon, kidney, oesophageal, pancreatic and cervical cancer has also been shown to be closely related to body weight. Ulrich points out that in Germany around 60 per cent of the population are at a greater than normal risk of developing cancer due to being overweight. For such people, weight reduction is an important preventive measure. However, weight loss should not be achieved through radical diets, but should be a result of slow progress: varied, healthy food (especially vegetables) and regular physical activity - about 30 - 60 minutes of light to challenging physical activities five times a week.
Sport reduces the dangerous intra-abdominal fat tissue in the abdomen. Several studies have shown that intra-abdominal fat plays a role in the development of inflammatory processes and is therefore also indirectly of great importance in the development of cancer. There is a high correlation between adiposity, which affects one in four people in Germany, and the presence of C-reactive protein (CRP), which is an important inflammatory parameter in blood. Sport intervention studies have shown that by doing physical training over a period of twelve months, overweight postmenopausal women significantly reduce the intra-abdominal fat tissue and the CRP blood values. Sport has also been shown to affect the hormone metabolism. Doing more sport is linked to lower levels of oestrogen. In addition, sport has also been shown to have a positive effect on immune function, vitamin D levels and DNA repair mechanisms. These aspects are currently being investigated at the DKFZ using gene expression analyses and proteomic methods. The results will be used to make prevention recommendations tailored as closely as possible to the individual requirements of patients.