Ash Larnder
Doctor of Philosophy in Population and Public Health (PhD)
Research Topic
The gut microbiome and hormone receptor-positive female breast cancer
G+PS regularly provides virtual sessions that focus on admission requirements and procedures and tips how to improve your application.
These videos contain some general advice from faculty across UBC on finding and reaching out to a potential thesis supervisor.
Dissertations completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest dissertations.
Purpose: Evidence for impacts of antihypertensive medication use on risk of colorectal cancer is mixed. We conducted an epidemiologic study to evaluate associations of five commonly prescribed classes of antihypertensive medications: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics with colorectal cancer risk.Methods: A systematic review and meta-analysis was conducted to appraise and synthesize previous epidemiologic studies of associations between anti-hypertensive medications and colorectal cancer risk. A systematic search for previously published studies was conducted in MEDLINE, Embase, Web of Science, and the Cochrane library (August 2021). Meta-analytic risk ratios (RRs) and corresponding 95% confidence intervals (95% CIs) were calculated using the inverse variance method. To address methodological limitations of previous studies, a population-based retrospective cohort study (n=1,693,297) was conducted using administrative health data captured for people living in the province of British Columbia (BC). Antihypertensive medication use was parameterized as; ever use, cumulative duration of use, and cumulative dose used. A new-user design was applied to minimize the influence of prevalent use of antihypertensive medications. Multivariate, time-varying cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs for associations between medication use and occurrence of colorectal cancer. Results: No significant associations of ACEIs, ARBs, BBs, CCBs or diuretics with colorectal cancer risk were observed in the meta-analysis. In the cohort, 28,460 incident cases of colorectal cancer were identified during the follow-up period (mean=12.9 years). Diuretic use (ever/never) was associated with increased risk of colorectal cancer (HR 1.08, 95% CI 1.04-1.12). However, no associations were observed when cumulative duration and cumulative dose of diuretic use were assessed. No significant associations between any of the other four classes of medications (ever use, cumulative duration and cumulative dose) and colorectal cancer risk were observed.Conclusion: The findings help to clarify associations between the five commonly prescribed classes of antihypertensive medications and colorectal cancer risk, suggesting that these antihypertensive medications are unlikely to influence colorectal cancer risk.
View record
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.
View record
Theses completed in 2010 or later are listed below. Please note that there is a 6-12 month delay to add the latest theses.
Background/Objectives: Demographic, health history, and lifestyle factors have been associated with prognosis of colorectal cancer (CRC), but the mechanisms underlying these associations remain poorly understood. Our primary objective was to explore the association of these factors with expression of two biomarkers in CRC, SPARC and PD-L1, for which lower and higher levels of expression, respectively, have been associated with poorer CRC prognosis. Methods: Participants were drawn from the British Columbia Generations Project (BCGP), who at time of recruitment, provided data on various demographic, health history, and lifestyle factors. Formalin-fixed paraffin-embedded blocks were obtained for 49 incident BCGP CRC cases and used to create tissue microarrays. Slides created from the microarrays were stained with SPARC and PD-L1 antibodies and analyzed to calculate H-scores as measures of expression in both epithelial and non-epithelial tissues. Linear regression analyses were used to evaluate associations between the various factors and ln-transformed H-scores.Results: In CRC tumour epithelium, smoking was associated with a 0.53-fold lower level of SPARC expression (p=0.05); a similar though non-significant, association was observed in non-epithelial tumour tissue. Higher income was associated with a 1.33-fold greater level of SPARC expression in tumor non-epithelial tissue (p=0.04); a similar effect was not observed in tumour epithelium. Higher stage was associated with a 0.74-fold lower level of non-epithelial tumour SPARC expression (p=0.04). A similar non-significant effect was observed in tumour epithelium. PD-L1 expression in tumour epithelium was 2.84-fold greater among females (p=0.005). A similar non-significant effect was observed in tumour non-epithelial tissue. History of CRC screening was statistically significantly associated with 2-fold greater levels of PD-L1 expression in tumour epithelial and non-epithelial tissues (p=0.04). Conclusion: Associations of SPARC expression with smoking, income, and stage, but not PD-L1 expression with biological sex and history of CRC screening, were consistent with the previously established associations of these factors with CRC prognosis. Larger scale studies with prognostic data are needed, but our results suggest that differences in expression of SPARC may contribute to the previously observed impacts of factors on CRC prognosis. However, additional work to understand the role of PD-L1 in CRC prognosis is needed.
View record
Background: Mental health disorders are highly prevalent in the Canadian population and has been associated with cancer risk; however, previous findings in literature are inconsistent (1–4). This study aims to elucidate the relationship between mental health disorders and cancer risk, as well as explore the potential mediating effects of lifestyle behaviours.Methods: A cohort study was conducted with 34,571 participants aged 40-69 years from the province of Quebec. Depression was conceptualized from the PHQ-9, antidepressant use, and either a positive screen from PHQ-9 scores, antidepressant use, or self-report of physician diagnosis. Anxiety was defined using the GAD-7, and co-morbid depression and anxiety was assessed using the PHQ-9 and the GAD-7. Cox proportional hazards regression models were used to investigate the association between mental health exposures and risk of prostate, lung, and all cancers combined. Mediating effects of health behaviours were assessed using Baron and Kenny mediation criteria., then a Quasi-Bayesian/Monte Carlo approximation was used to obtain confidence intervals. Results: For risk of all cancers combined, there was a modest positive association with all mental health exposures, however none reached significance with full adjustment. No relationships reached significance for prostate cancer. There were positive associations between mental health disorders and lung cancer risk, but only anxiety and lung cancer in women was significant with full adjustment (HR = 1.67, 95% CI: 1.01-2.76). Women had consistently higher risk estimates than men for all cancer and lung cancer risk for the majority of exposures. Smoking status mediated the relationship between depression (PHQ-9) and lung cancer, anxiety and lung cancer, and co-morbidity and lung cancer by 27%, 18%, and 26%, respectively in women. In men, smoking status mediated 17% of the relationship between depression (PHQ-9, antidepressant use, or self-report of physician diagnosis) on all cancers. Conclusions: Positive associations were observed between mental health disorders and overall and lung cancer risk, however few relationships reached significance. Risk estimates were generally higher in women than in men, suggesting a differential risk. Smoking status mediated a significant proportion of the relationships between mental health disorders and cancer risk.
View record
Background: The Food Explorers (FE) program was designed and developed for use with kindergarten and grade 1 children. Offered within the classroom setting, the program aims to encourage children to identify and experience a wide variety of foods. The objective of this study was to examine the impact of the program on children’s willingness to try new and familiar foods. Methods: A quasi- experimental pre-post design was employed to evaluate the impact of the program on children’s familiarity and willingness to try novel and familiar test foods. Children in the FE group participated in food -related classroom activities led by teachers, over 5 months and the control group were taught the standard curriculum. Assessments of familiarity and willingness to try foods was completed at baseline and after 5 months in both groups. Parent-perceived food neophobia was also assessed using a validated scale at both times. Open-ended questions were used to assess parent and teacher experience with the program. Results: Analyses were conducted with 194 children (FE group, n=102 and control group, n=92). Knowledge of familiar foods increased over time in both groups and a significant group by time interaction was observed with 2 test foods (out of 10) at follow-up, indicating increased knowledge in the FE group, compared to the control group. Willingness to try the test foods, measured as food preference scores significantly increased for five novel foods in the FE group compared to the control group. No significant difference was observed in parent-perceived food neophobia scores between groups. Parents indicated positive experiences with respect to their children’s willingness to try new foods at home. Positive experiences were also noted by the teachers.Conclusion: While there is some evidence to suggest that the FE program may positively impact food knowledge and willingness to try new foods in kindergarten and grade 1 children, limitations of the study and implementation of the FE program warrant consideration when considering the impact of the program. The findings of the study provide valuable information on barriers for implementation of the FE program in classrooms and will inform future evaluations of the program.
View record
Background: Cancer survivors may be motivated to change their diet for weight management and improved survival. However, dietary behaviours and obesity are influenced by a range of individual-level and environmental factors rather than simply individual choices. This study aims to understand the diet quality of cancer survivors and its association with obesity and neighbourhood environment in comparison to non-cancer controls.Methods: A cross-sectional study was conducted with 19,973 participants aged 35 to 69 years from Atlantic Canada. A healthy eating index (HEI) was used to evaluate diet quality using dietary intake collected from a food frequency questionnaire. Obesity was assessed using anthropometric and bio-impedance measures. Neighbourhood environment data were derived from the Canadian dissemination-area-level census data. Multivariable multi-level models were used to investigate HEI and its association with obesity in cancer survivors compared to non-cancer controls. The associations between neighbourhood deprivation, population density and HEI were also explored. Results: Cancer survivors (n = 1930) had a higher mean HEI than non-cancer controls (mean difference: 0.45, 95% CI [0.07, 0.84]). Body mass index, waist circumference, waist-to-hip ratio, body fat percentage, and fat-free mass index were not associated with HEI, while trunk fat percentage had a weak positive association with HEI (0.45, 95% CI [0.08, 0.83]). The diet-obesity relationship did not significantly differ by cancer status. Mean HEI was lower in the most compared to the least socially deprived neighbourhoods (-0.56, 95% CI [-0.88, -0.25]), and in the most compared to the least dense neighbourhoods (-0.39, 95% CI [-0.77, -0.01]), but was not associated with material deprivation. Associations between diet quality, material deprivation and population density significantly differed by urbanicity. In rural areas, diet quality decreased with increasing material deprivation and decreasing population density, while the reverse was true for urban areas. Conclusion: Cancer survivors had a slightly better diet quality than non-cancer controls, but both groups are in need of dietary improvement. Diet was not associated with obesity measures in the cancer and non-cancer groups but was associated with neighbourhood deprivation and population density with evidence of urban-rural differences, suggesting the complexity of dietary behaviour and the need for multi-level interventions.
View record
If this is your researcher profile you can log in to the Faculty & Staff portal to update your details and provide recruitment preferences.