Identifying metabolic features of colorectal cancer liability using Mendelian randomization.

Background: Recognizing the early signs of cancer risk is vital for informing prevention, early detection, and survival. Methods: To investigate whether changes in circulating metabolites characterise the early stages of colorectal cancer (CRC) development, we examined associations between a genetic risk score (GRS) associated with CRC liability (72 single nucleotide polymorphisms) and 231 circulating metabolites measured by nuclear magnetic resonance spectroscopy in the Avon Longitudinal Study of Parents and Children (N=6,221). Linear regression models were applied to examine associations between genetic liability to colorectal cancer and circulating metabolites measured in the same individuals at age 8, 16, 18 and 25 years. Results: The GRS for CRC was associated with up to 28% of the circulating metabolites at FDR-P<0.05 across all time points, particularly with higher fatty acids and very-low- and low-density lipoprotein subclass lipids. Two-sample reverse Mendelian randomization (MR) analyses investigating CRC liability (52,775 cases, 45,940 controls) and metabolites measured in a random subset of UK Biobank participants (N=118,466, median age 58y) revealed broadly consistent effect estimates with the GRS analysis. In conventional (forward) MR analyses, genetically predicted polyunsaturated fatty acid concentrations were most strongly associated with higher CRC risk. Conclusions: These analyses suggest that higher genetic liability to CRC can cause early alterations in systemic metabolism, and suggest that fatty acids may play an important role in CRC development. Funding: This work was supported by the Elizabeth Blackwell Institute for Health Research, University of Bristol, the Wellcome Trust, the Medical Research Council, Diabetes UK, the University of Bristol NIHR Biomedical Research Centre, and Cancer Research UK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work used the computational facilities of the Advanced Computing Research Centre, University of Bristol - http://www.bristol.ac.uk/acrc/.

Health behavior change benefits: Perspectives of Latinos with serious mental illness.

The objective of this study was to explore the perceived benefits of engaging in health behavior change from the viewpoint of overweight and obese Latinos with severe mental illness (SMI) enrolled in the U.S. Qualitative, semistructured interviews were conducted with 20 obese Latinos with SMI who were enrolled in a randomized trial evaluating the effectiveness of a motivational health promotion intervention adapted for persons with SMI. Overweight and obese Latino participants believed that engaging in health behavior change would have both physical and mental health benefits, including chronic disease management, changes in weight and body composition, and increased self-esteem. Interventions that explicitly link physical activity and healthy eating to improvements in mental health and well-being may motivate Latinos with SMI to adopt health behavior change.

Perspectives of Overweight Latinos with Serious Mental Illness on Barriers and Facilitators to Health Behavior Change.

Serious mental illness (SMI) and Latino ethnicity can produce a compounded health disparity, placing individuals at particularly high risk for excess morbidity and premature mortality. Culturally sensitive strategies are needed to improve health behaviors, including exercise and healthy eating within this population. The purpose of this qualitative study was to explore facilitators, barriers, and preferences for health behavior change among Latinos with SMI. Semi-structured interviews were conducted with 20 Latinos with SMI who were enrolled in a randomized trial evaluating the effectiveness of a motivational health promotion intervention, In SHAPE. The interviews explored perceived facilitators and barriers to health behavior change, focusing on the role of family, and exercise preferences. The primary facilitator identified by participants was having someone (either professional or significant other) to hold them accountable for engaging in healthy behaviors. A major barrier to making lasting health behavior change was cultural influences on food. Participants preferred aerobic exercises set to music that kept their minds occupied in contrast to strenuous activities such as weight lifting. This exploratory research provides insight into the perspectives, experiences, and preferences of Latinos with SMI participating in a health promotion intervention. Findings will be used to inform future health promotion efforts adapted to meet the needs of an ethnically diverse, underserved community.