Grant: Operating Grant: CCS Innovation Grants

The Problem: The Canadian Cancer Society, as well as other health agencies emphasize the importance of a healthy lifestyle for cancer prevention. About one-third of cancers can be prevented by maintaining a healthy weight, eating a diet rich in fruits and vegetables, being physically active and limiting alcohol consumption. However, in Canada the rates of overweight and obesity remain high, consumption of fruit and vegetables has declined, less than 15% of adults meet physical activity recommendations and 80% consume alcohol. A large survey of adults found nearly 50% felt “it seems like almost everything causes cancer” and a recent study suggested the majority of cancers are due to “bad luck”. An understanding of mechanisms linking preventative behaviour and cancer is critically needed to move the field forward. Metabolomics is the study of chemical fingerprints that cellular processes leave behind, specifically endogenous and exogenous small molecule profiles. New technology such as nuclear magnetic resonance (NMR) provides robust, high throughput, quantitative measure of hundreds of unique metabolites. Hypothesis: There will be distinct metabolic profiles associated with preventive behaviours: healthy weight, fruit and vegetable consumption, physical activity and alcohol consumption. Further, metabolic profiles will differ between individuals who engage in multiple versus single or no preventive behaviours. Overall Study Aim: To use metabolomics to characterize metabolic profiles of lifestyle-related preventive behaviours in adults. Aim 1: Metabolite profiles will be characterized for each lifestyle-related preventive behaviour: healthy weight, consumption of at least 5 fruit and vegetables per day, no more than 2 alcoholic drinks (men) or 1 (women) and at least 30 minutes of moderate-to-vigorous activity on 5 days of the week. Aim 2: Metabolites will be compared between people according to the number of preventive behaviours they engage in. Aim 3: To determine the relevance of metabolites identified in aims 1 and 2 to cancer development. Methods: 1,200 adults without a history of cancer will be selected from the BC Generations Project (BCGP), a study of men and women aged 35-69 from across British Columbia. Between 2009 and 2014 nearly 12,000 adults completed questionnaires, had physical measurements and provided blood samples. The amount and type of physical activity was assessed from validated surveys. Adiposity measures include measured height and weight, waist circumference and % body fat from bioelectrical impedance. The number of fruits and vegetables and alcoholic drinks typically consumed were selfreported. A high-throughput, automated assay will quantitatively measure metabolites in stored plasma including metabolites from the following classes: lipids, organic acids, organoheterocyclic, organooxygen and nucleosides. The human metabolome database (HMD) contains data on ~49,000 metabolites including origin, biofunction, metabolic and disease pathways and associated disorders and diseases. Metabolites identified in aims 1 and 2 will be referenced with the HMD and prior literature to determine relevance to cancer. Significance: With the aging population, the burden of cancer in Canada will increase exponentially. There is thus a clear and immediate need for prevention to control cancer. These results may identify new biomarkers correlated with preventive behaviours that are potentially relevant for biological processes leading to cancer development. This can help guide future targeted studies that consider these metabolites as mediators or targets that impact cancer. Studying adults in the BCGP provides unique opportunities to develop findings due to linkage to provincial health registries and national data from other cohorts of the Canadian Partnership for Tomorrow Project, which could be used to validate our