Trevor Dummer

Background: Certain diabetes medications have been linked to reduced risk of breast, colorectal, and pancreatic cancers, although findings are inconclusive, reflecting limitations in the methodology of previous studies. Objective: To evaluate associations between classes, subclasses and individual diabetes medications, and risks of breast, colorectal, and pancreatic cancers. Methods: Using linked administrative health data from the Province of British Columbia, a cohort of over 3 million people aged 35-100 (1996-2019) was constructed. Diabetes medication use was parameterized as binary, continuous, and categorical variables. Duration-response and dose-response associations were determined using cumulative duration and cumulative dose (years receiving the defined daily doses). Medication use was treated as time-varying, with a 1-year lag, over the follow-up period. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between new use of diabetes medications and occurrence of breast, colorectal, and pancreatic cancers. In a subset of participants from the British Columbia Generations Project (BCGP), risk estimates were further adjusted for sociodemographic and lifestyle variables. An active comparator analysis was employed to mitigate confounding by indication. Results: Metformin (HR=1.04, 95%CI=1.04-1.05) and insulin secretagogues (HR=1.02, 95%CI=1.01-1.02), especially gliclazide and glyburide, were found to be linked to an increased risk of colorectal cancer. A higher dose of basal insulin was associated with a higher pancreatic cancer risk (HR=1.05, 95%CI=1.04-1.06). Conversely, ever use of SGLT-2 inhibitors was related to a lower breast cancer risk than never use (HR=0.64, 95%CI=0.48-0.85). Many of these associations persisted after adjusting for sociodemographic and lifestyle factors in the BCGP subset. In the active comparator analysis, similar associations were identified when compared to alternative diabetes medications. Conclusion: Multiple diabetes medications were associated with breast, colorectal, and pancreatic cancer risk, highlighting the possible need to consider long-term health implications of these commonly prescribed medications.

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Background: Health behaviours play a pivotal role in the primary and secondary prevention of colorectal cancer (CRC), and are a modifiable determinant of survivorship in CRC patients. However, adherence to recommended health behaviours, including physical activity and healthy body mass index (BMI) maintenance, is sub-optimal. This dissertation contributes to the understanding of individual-level factors that influence CRC prevention-related behaviours, the impact of a CRC diagnosis on these behaviours, and how these behaviours might be improved in CRC survivors. Methods: Baseline data from the British Columbia Generations Project (BCGP) were used to examine adherence to World Cancer Research Fund (WCRF) recommendations for cancer prevention. These data were also combined with follow-up data, and cancer registry data, to examine longitudinally the impact of a diagnosis of cancer, CRC or otherwise, on a subset of these behaviours. Additionally, a systematic mixed studies review was conducted to synthesize available literature concerning behaviour change interventions in CRC survivors. Results: Overall adherence to WCRF recommendations was relatively high in the BCGP cohort, though it was markedly lower for diet-related behaviours. Some clustering of low adherence with other risk factors for CRC, such as low socioeconomic status, was identified. The longitudinal analysis found CRC was not predictive of significant change in two cancer prevention recommendations regarding alcohol consumption and BMI between baseline and follow-up. The systematic mixed studies review identified tentative evidence that behaviour change interventions can improve CRC survivor health behaviours, and that members of this group have clear preferences regarding intervention content. However, a paucity of available evidence and a tendency towards poor specification of intervention content was common. Conclusion: These results offer novel contributions regarding targets for future interventions and research to improve health behaviours in the general population and in CRC survivors. Further research is needed to ensure the design of any such interventions are grounded in theory and evidence, and informed by patient preferences and contextual considerations.

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Livestock are critical to the livelihood of up to two billion global poor and thus represent an ideal focus for poverty amelioration. For traditional keepers, livestock are: culturally significant, nutritionally important, and serve as “daily currency” and household “savings”. However, they may also increase infectious disease risk, especially via zoonoses which can reduce both human and livestock health and quality of life. Although many studies exist on livestock-dependent communities, including the Maasai and other pastoralists, significant knowledge gaps persist regarding the relationships between traditional livestock-keeping and human wellbeing.This dissertation investigated associations between pastoral livestock and owner health through a series of cross-sectional and longitudinal studies conducted in Olkoroi, a rural Maasai community. The objectives were to: 1) review the literature on connections between livestock health and productivity, and human wealth, health and wellbeing; 2) describe Olkoroi sociodemography and capital; 3) assess local human and livestock disease priorities and livelihood challenges; 4) conduct longitudinal studies of livestock growth, livestock and human infectious disease; 5) measure adult psychological wellbeing; and 6) use the collected data to build predictive models of human wellbeing, herd size, livestock growth, livestock and human infectious disease frequency.I found livestock were the primary livelihood and predicted psychological wellbeing, but 40% of households, primarily female-headed, had insufficient animals to support themselves. Men and women identified similar factors affecting wellbeing but differed in proportional attribution: women uniquely spoke of restrictions on autonomy. Community disease prioritizations were similar to national priorities, however, disease management was inconsistent and causal understanding was low. Households self-rated husbandry practices highly, but felt financial constraints prevented adoption of best practice. Household variables were associated with herd size, but climate was the best predictor of livestock growth, and livestock and human infectious disease: livestock disease prevalence did not predict human disease. My results suggest livestock research must prioritize gender and local context to better understand livestock-human health relationships. Claims about the contribution of livestock to human disease burdens must also be clarified through more consistent research frameworks which allow inter-study comparisons, and more longitudinal studies to better identify causal relationships between exposures and disease incidence.

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