Title: Rapid, high-throughput immunochemical techniques to measure (adducted protein) biomarkers of heterocyclic amine (HCA) exposure
Funder: World Cancer Research Fund

Abstract: When meat and fish are cooked above 100 degrees centigrade, chemicals are produced called heterocyclic amines (HCAs). When we eat these foods we consume HCAs. To date, it has been difficult to measure how much HCAs are in our bodies because they are quickly changed to other compounds and are not present in blood or urine long enough to be measured. As well as being difficult to measure in the body, they are also difficult to measure in foods because so many aspects of cooking and food preparation can affect the levels of HCAs formed. In laboratory experiments, some of these HCAs have been shown to increase the risk of cancer. Some human studies also suggest a high intake of these HCAs increase a person’s cancer risk, although this is not consistently shown. This lack of consistency may be due in part to the difficulties in measuring HCAs in both food and body fluids. Therefore, we need a method of measuring HCAs in the body which can overcome these difficulties. A proportion of HCAs when consumed will become attached to DNA and protein in our bodies. This binding produces another compound called an adduct. These adducts have been shown in previous research to be a key compound in the development of cancer. Thus HCA adducts (of either DNA or protein) may be a good reflection of how much HCAs have been consumed in the diet but these adducts also remain in the blood for a long enough time to be measured. To date, methods have been developed to measure HCA protein adducts but they are expensive. By developing a more cost-effective method more blood samples could be analysed (including stored samples from studies which have collected other useful data on dietary intake and lifestyle factors that could also be related to cancer risk). This would help scientists to more fully understand what aspects of our diets and lifestyle affect HCA levels in the body and therefore develop guidelines that may reduce cancer risk. The aims of this study are: 1.To develop a cost-effective method for measuring HCA protein adducts (using antibodies and biosensors) 2.To test the validity of this new method by carefully measuring HCA dietary intakes in healthy volunteers and comparing these levels to HCA adduct levels 3.To further test the validity of this method we will identify human participants from the first study (aim 2 above) with the highest (group 1) and lowest (Group 2) HCA intakes and assign them to a low HCA diet (in the case of Group 1) and a high HCA diet (in the case of Group 2) for 6 weeks. The resulting change in HCA adduct levels will be then be measured.4.Using stored blood samples from 2000 adolescents, HCA adducts will be measured. There is already a lot of information collected on their diet, lifestyle and health status. All of this data will be analysed to investigate if HCA adducts levels are related to what the adolescents eat (ie. their total dietary pattern).


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS