Approved Research Projects

2021 Approved Projects

2020 Approved Projects

Microbes are small organisms such as bacteria that can live within and on the human body. These groups of microbes have been shown to play important roles in maintaining human health. Some microbes that can inhabit the body can cause disruptions that contribute to the development of chronic diseases such as cancer. One area these microbes reside is within the human oral cavity where they have been linked with certain types of cancer. However, there is currently a lack of studies that have examined the community of oral microbes in a large group of individuals that have gone on to develop cancer. Identifying microbes that are predictive of future cancer development could aid in the discovery of new risk factors for cancer development. To address this, we will study the role of oral microbes in the development of specific types of cancer using a large Canadian cohort known as the Canadian Partnership for Tomorrow’s Health (CanPath). At baseline, before cancer development, participants donated saliva samples and provided detailed information about their health status, physical measures, and lifestyle choices. Since then a subset of these individuals have developed some form of cancer. With the oral saliva sample, we can use DNA sequencing approaches along with machine learning and statistical models to study the microbes that reside within our bodies. By comparing samples from individuals that have developed cancer to healthy controls, we will attempt to detect unique microbial features that are associated to the development of certain types of cancer. The results of this study will provide important information about the usefulness of accessing oral microbes as possible way to forecast individuals at a higher risk of developing cancer.
Colorectal cancer (CRC) is the third most common cancer in Canada and is responsible for the second most cancer-related deaths. Despite a decrease in the incidence of CRC among older age groups, an increase in the incidence of CRC for adults under the age of 50 has been observed in Canada and the United States, but the reasons for this remain unclear. Adults under the age of 50 diagnosed with CRC tend to have poorer survival because they are not routinely screened, thus are often diagnosed with advanced-stage of cancer. CRC in older adults has been studied extensively, but comparatively, little is known about risk factors for young-onset CRC. The Canadian Partnership for Tomorrow’s Health (CanPATH) is Canada’s largest population cohort study that was developed to explore relationships between lifestyle, genetic, and environmental factors and chronic disease outcomes. In this project, we will use data from two sub-cohorts in CPTP (Alberta’s Tomorrow Project and Ontario’s Health Study) to examine risk factors of young-onset CRC (< 50 years of age). Results generated in this project will improve our understanding of CRC risk factors in younger adults, leading to improved prevention strategies for young adults at elevated risk of CRC.
Breast cancer is the most common type of cancer that occurs among females and a leading cause of deaths worldwide. Several studies suggest the involvement of viruses in the development of breast cancer and these include a group of viruses known as betaretroviruses. Retroviruses are made up of RNA and with the help of an enzyme, called reverse transcriptase, have their RNA transcribed into DNA which is then integrated into the DNA of the infected cells to make copies of themselves. To establish Human Betoretrovirus (HBRV) as a potential causative agent of breast cancer, infection must be observed before the development of the disease. By using serum samples of patients who donated their blood samples before developing breast cancers, our study aims to determine whether these patients had the evidence of HBRV infection before developing breast cancer.
Breast cancer is the most common cancer and second leading cause of cancer death in Canadian women. A woman faces a one in eight chance of developing the disease in her lifetime. Currently, most provinces in Canada recommend that women aged 50 to 74 have a mammogram every 2 to 3 years. Risk stratified screening seeks to maximize the benefits and reduce harms of screening, by screening women based on their estimated risk of disease. Risk predication tools like the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) are used to estimate a women’s risk of breast cancer. The risk of breast cancer varies by geographical region, as does the distribution of lifestyle/hormonal risk factors. Understanding this information is important for accurate risk predication in specific populations. Our first objective is to customize BOADICEA to the Canadian context using CanPath data (with supplemental data from individual cohorts including ATP). Our second objective is to assess whether BOADICEA accurately predicts breast cancer risk in Canadian women. This information can then be used to improve breast cancer screening programs.

2019 Approved Projects

Cancer is the most common cause of death in Canada. In the past several decades, epidemiological investigations have been very successful in identifying risk factors for caner. About 70 years ago, the establishment of the association between smoking and lung cancer has resulted in mounting research evidence that has led to policy change in reducing population level cancer burden. Lack of physical activity is the second leading risk factor for cancer in Canada, and 150 minutes of moderate-to-vigorous intensity physical activity has been recommended to the general population for health promotion and cancer prevention. However, physical activity can be carried out in four distinct domains: household, transport, occupational, and leisure-time, for which no recommendation is available specific to occupational group. Previous cancer prevention research on occupational physical activity has primarily focused on occupational sitting, pointing to the heightened cancer risk due to lack of physical activity at work. Very recently, a few studies (mostly European-based) reported a detrimental impact of heavy occupational physical activity on cardiovascular outcomes, suggesting a health paradox between occupational and leisure-time physical activity. Occupational activity that involves heavy physical work can be demanding and long-lasting, often with limited recovery time. Physical activity at leisure time, on the other hand, is usually carried out voluntarily, in shorter bouts (less than a couple of hours), and with sufficient recovery. Given the different characteristics of occupational and leisure time physical activity, it is possible that they induce different physiological responses in the human body, thus leading to contrasting health consequences. Little is known on the paradoxical cancer risk in relation to occupational and leisure-time physical activity. This is primarily due to the physical activity assessment used in many cancer risk investigations, which frequently studied leisure-time physical activity alone. Although there is no existing data in Manitoba as of yet, utilizing data from Alberta’s Tomorrow Project, we aim, for the first time, to exam the joint impact of occupational and leisure-time physical activity on cancer risk in a large cohort of more than 30,000 individuals. Supported by the full spectrum detailed assessment of domain-specific physical activity, we will also assess other endpoints including diabetes and cardiovascular disease. Such information are particularly useful to 1) develop specific guidelines for workplace physical activity, 2) facilitate epidemiological study design among Manitoba workers on the physical activity paradox (particularly within the newly launched Manitoba Tomorrow Project), 3) and to plan and evaluate strategies to prevent cancer specific among specific occupational groups.
The Canadian Cancer Society estimates that 25,000 new breast cancer (BC) cases will be diagnosed in Canada in 2015, with 2300 of them in Alberta. While people cannot control many of the factors contributing to cancer (eg, genetics), they can potentially control many Health and Life Style (HLS) factors -- such as exercise, weight, alcohol consumption, etc -- which collectively are believed to contribute significantly. By modifying these factors, women might be able to delay, or even prevent, the onset of BC. To understand risk factors and indicators for onset of breast cancer, Machine Learning “survival prediction” tools will be used to learn, from ATP data of women (both healthy women and those with BC), to predict the “time to BC onset” for a woman who is currently BC-free. Many of the existing prediction models, such as the Gail model, include mostly non-modifiable risk factors. Therefore, this project aims to develop a new personalized prediction model for breast cancer that can provide an understanding of the impact of modifiable risk factors on the onset of breast cancer. The magnitude of the impact can be shown as modifiable risk factors are increased, reduced or eliminated from a person’s lifestyle.
Alberta’s Tomorrow Project (ATP) is a longitudinal cohort study that has been following the health of 55,000 Albertans since the year 2000. ATP is aiming to understand what factors are associated with the development of cancer and chronic diseases in a representative Albertan population. In a study of this size and duration, participants being lost during follow-up procedures is a normal occurrence. Loss-to-follow-up happens for a variety of reasons – participants may simply no longer be interested in responding to requests for data, they may have moved, become ill, or potentially passed away, among other reasons. Our goal is to understand the demographics of participants that still remain actively engaged in the cohort and those that are not, as well as to understand characteristics that may be associated with becoming lost to follow up. Descriptive statistics will be run to understand the sociodemographic, lifestyle, and disease states of individuals who remain actively engaged in the cohort. These same characteristics will be included in statistical models to see what characteristics are most strongly associated with loss-to-follow-up. This information will be used internally at ATP to develop targeted strategies to re-engage individuals who are lost-to-follow-up, or to potentially recruit new participants if a certain subgroup is disproportionately lost and unable to be re-engaged. This knowledge will also be published and shared with other longitudinal studies to help them to understand which characteristics are associated with loss-to-follow-up and allow them to include this knowledge in their planning.
The objective of our ‘CAnadian Network for Advanced Interdisciplinary Methods for comparative effectiveness research’(CAN-AIM) team is to enhance the validity and accuracy of Canadian research on real-life comparative effectiveness and safety of drugs. Comparative effectiveness research is the direct comparison of existing therapies in order to understand which treatment works best for which patients, and, additionally, which treatments pose the greatest potential harms. To do so we are responding to queries on the drug safety and efficacy of medications on conditions such as hypertension, diabetes, rheumatoid arthritis, rheumatic diseases and inflammatory bowel disease, and cancer. Our specific mandate is to use a combined approach, with both clinical cohort data and administrative data, to produce timely answers to these questions, using prospectively collected data. In order to facilitate this, we are working with the provincial directors of British Columbia, Alberta, Ontario, Quebec, and the Atlantic provinces contributing to the Canadian Partnership for Tomorrow Project (CPT).
In Canada, 1 in 2 people will be diagnosed with cancer during their lifetime, with lung and prostate cancer being two of the most common cancers diagnosed. Many of these cancers may be prevented through lifestyle changes, including changes to diet and physical activity levels. However, the link between lifestyle and cancer is poorly understood. Only age, race and family history are well-known risk factors for prostate cancer and little is known about modifiable risk factors for lung cancer beyond smoking. The project aims to carry out a series of studies to identify the lifestyle, environmental, and genetic factors that may increase the risk that a person will be diagnosed with lung or prostate cancer. Using data from the Canadian Partnership for Tomorrow Project, we aim to investigate known and potentially new risk factors for prostate and lung cancer collected from physical measurements, questionnaires, and blood samples, including medical history, lifestyle (diet, body size, sleep, physical activity), and environmental factors (e.g. exposure to toxins). Cancer development was determined over 9 years, during which time more than 800 lung and prostate cancers were diagnosed. People who were diagnosed with cancer will be matched with a person of the same age, sex, race, and family history of cancer for comparison. Statistical modeling will be used to identify new risk factors that may help identify people who are at risk of developing cancer. This information will inform the design of interventions to prevent these cancers in the future and improve the health of Canadians.
The global prevalence of major chronic diseases poses significant risk for individual health, growing economic burden to families and the healthcare systems, and mounting national challenges for cost-effective and sustainable utilization of finite healthcare resources. Reliable determination of potential prospective healthcare cost is a key step for appropriate management and planning of finite healthcare resources. Prospective healthcare cost can be assessed indirectly by a combined approach of predicting future clinical outcomes and assessing the current state of incident-based healthcare cost. Probability-based risk prediction has been adopted in healthcare to predict future clinical outcomes. The performance of disease risk prediction models in the literature varies, due to many factors such as source population, demographic, genetics, etc. In order for results from risk prediction models to be used to support decision-making in the area of individualized medicine and healthcare utilization, the models will have to be properly validated. To increase the performance of the risk prediction models, many challenges will have to be addressed. Among these challenges, representative and reliable datasets would be the primary consideration. The Canadian Partnership for Tomorrow Project (CPTP) is Canada’s largest prospective population cohort with over 300,000 cancer-free participants at enrollment. The large sample size in this cohort with a longitudinal data structure forms an ideal platform for developing risk prediction models in the Canadian population for major chronic diseases, such as cancer, cardiovascular disease, and type 2 diabetes. In addition, linkage with health administrative data makes it possible to perform healthcare cost analysis based on the health outcome predictions and service utilization. Machine learning (ML) will be applied to build the prediction model and 10-fold cross validation will be employed for model validation. The validated model-based cost analysis can then provide evidence to inform decision making, such as healthcare resource allocation and underscore the importance of resourcing for population-level disease prevention efforts. With the algorithm proposed in this study, we can also directly assess the impact of these adherence behaviors on healthcare costs.
Population level interventions, such as those that involve designing and developing health supportive built environments, are needed to reduce the incidence of modifiable chronic health conditions including clinical risk factors for cardiovascular disease. However, the extent to which the neighbourhood built environment, and in particular walkability, translate into better cardiovascular health for residents remains unknown. The primary objective of this study is to determine the extent to which the neighbourhood built environment is associated with cardiovascular-related clinical and physical risk factors (blood glucose, cholesterol, blood pressure, and weight status) in adults. The findings from this study have the potential to inform urban planning policy and public health interventions.

2018 Approved Projects

There is substantial evidence that cardiovascular disease (CVD), including angina, heart attack, and stroke, are associated with smoking. Several studies have shown an accumulation of cardiovascular risk factors in smokers, indicating a higher susceptibility to CVD (Jenei et al 2000; Gikas et al 2016; Haddad et al 2016). Physical activity, on the other hand, contributes to primary and secondary prevention of several chronic disease, including CVD (Physical Activity Guidelines Committee (2008); U.S. Department of Health and Human Services (1996)), and is associated with a reduced risk of CVD death and all-cause mortality (Wartburton et al 2006).

The independent and opposing effects of tobacco smoking and physical activity on CVD risk are well documented but it is of interest to determine if physical activity mitigates the impact of smoking on CVD risk. In this study, we hypothesize that the increased risk of CVD events in smokers compared to non-smokers is lower at increasing amounts of physical activity compared to low physical activity levels. For example, greater physical activity levels could potentially reduce the increased risk of CVD events in smokers compared to non-smokers from 60% to only 30%.

A limited number of studies have assessed the interaction effect between physical activity and smoking status on CVD risk (Teramoto et al 2015; Linke et al 2009; Lee et al 2001 ). However, these studies have focused on leisure time physical activity, exercise capacity and energy expenditure respectively, which do not capture all domains of physical activity. Moreover, most of these studies only used specific people in a population which limits generalizability.

In this study we propose a unique, multi-component comprehensive approach that has not been utilized before in a single study to further explore the interaction effect between physical activity and smoking status on CVD event risk among men and women in Alberta’s Tomorrow Project (ATP). Aside from including interaction in statistical analysis, the proposed research will consider all four domains of physical activity: occupation, transportation, household and leisure/recreational, as well as pack years of smoking (“pack years” defined as number of packs per day for a certain period of time).

The aim of this study is to investigate the influence of physical activity on the association between smoking status and CVD risk among participants in Alberta’s Tomorrow Project (ATP) who are free of CVD at baseline but develop CVD during the course of follow-up.

The objectives of the study are to determine the following in ATP cohort participants:

Whether the added risk of CVD events in smokers -compared to non-smokers- is lower at increasing amounts of physical activity compared to low physical activity levels. We also propose an exploratory study to evaluate the use of 2 different physical activity instruments: Past-Year Total Physical Activity Questionnaire (PYTPAQ) and International Physical Activity Questionnaire (IPAQ), to assess changes in physical activity. This information would be used to inform the development of subsequent analysis investigating how changes in physical activity and smoking over time influence CVD risk.

Breast cancer is the most commonly diagnosed cancer among Canadian women, accounting for over 25% of cancers. High dietary consumption of fish, containing the omega-3 long chain polyunsaturated fatty acids (n-3 LCPUFA), have been associated with a reduced incidence of BC. However these findings have not been translated into recommendations, and one of the issues cited is that there is a lack of direct measures of n-3 LCPUFA fatty acid status.

The overall goal is to use data and samples from Alberta’s Tomorrow Project (ATP) and BC Generations Project (BGP) to identify the association between n-3 LCPUFA in the diet and in the blood and breast cancer risk.

Detailed dietary information is available from 16,782 ATP women and was completed prior to diagnosis of breast cancer (n=461 cases); detailed diet information is not available from BGP participants. In this sub-sample of ATP participants, we will investigate the association between reported dietary intake of n-3 LCPUFA and risk of breast cancer. To assess the relationship between plasma n-3 LCPUFA status and the risk of breast cancer, we will use a nested case-control study design, while controlling for other factors that modulate breast cancer risk. There are 394 participants in the ATP and BCGP cohorts who were diagnosed with breast cancer after donation of plasma sample. We will identify 2 age-matched controls for each woman with breast cancer matched from the cohort where the case was identified (n=1182 total of 788 women control women). Using a banked plasma sample, plasma PL fatty acid concentration and relative composition will be measured by isolating the lipids, separating the PL by thin layer chromatography and determining the fatty acid composition using gas liquid chromatography (see attached documentation Kaplan et al. 2012).

Modifying the built environment is a population health intervention that can shape physical activity levels. Systematic reviews find consistent positive associations between physical activity and neighbourhood “walkability” (determined from built characteristics such as land use mix, street connectivity, and residential density). Importantly, our understanding regarding the relationship of the built environment and physical activity is derived mainly from cross-sectional studies that are unable to provide evidence regarding the temporality of the relationship. This study will examine the extent to which changes in neighbourhood walkability, due to a participant’s residential relocation, impact their walking undertaken for different purposes. Specifically, we will: 1) estimate the effect of a change in neighbourhood walkability on transportation and recreational walking and 2) assess the extent to which the researcher-defined geographical area of the neighbourhood impacts the estimated associations. We will use existing data from Alberta’s Tomorrow Project. Our sample will include participants who completed two sets of surveys assessing physical activity, perceived neighbourhood walkability, sociodemographic, and health characteristics. We will geocode each participant’s household address and use Geographical Information Systems to estimate 400m and 1600m walksheds (i.e., polygons). Using spatial data, we will create a “walkability” index for each walkshed. Participants will be allocated to either a quasiintervention or a control group according to their relocation status and change in walkability (move resulted in higher walkability; move resulted in lower walkability; move resulted in no change in walkability, or no relocation). To adjust for group differences in the covariates, propensity scores estimated from a multinomial model predicting group membership, will be used as sampling weights in generalized linear models estimating group differences in walking change scores. In addition to the longitudinal analysis, we will also undertake cross-sectional analysis to estimate linear and nonlinear associations between the walkability and self-reported built characteristics and walking. This natural experiment will provide important causal evidence about the relationships between walkability and walking and provide evidence for planners and policymakers for creating pedestrian supportive neighbourhoods.

Solar ultraviolet radiation (UVR) is a ubiquitous exposure that can be both beneficial and detrimental to cancer initiation depending on the magnitude and type of exposure. The causal relationship between exposure to UVR and melanoma and non-melanoma skin cancers (basal and squamous cell carcinoma [NMSC]) is established. Melanoma is typically associated with intense intermittent periods of sun exposure, while NMSC tends to develop from chronic sun exposure. A certain level of sun exposure is potentially protective for some other cancer sites through the production of vitamin D. However, a strong body of evidence supports an association of the occurrence of NMSC with elevated risk for developing other cancers (particularly hematologic malignancies), providing some evidence of a potential relationship between chronic sun exposure and risk for other cancers sites. The assessment of risk associated with ambient UVR, time spent in the sun, and sun behavior habits (sunburn and sunbathing) with non-cutaneous site specific cancer development remains limited in large longitudinal studies. The objectives of the approved study are to use data collected by the Albert’s Tomorrow Project (ATP), the Ontario Health Study (OHS), and CARTaGENE from over 245,000 participants to: (1) investigate whether there is a U shape relationship of sun exposure with the risk of developing hematologic malignancies; (2) whether there is a synergistic interaction between ambient UVR and personal sun exposure on the risk of developing hematologic malignancies; and (3) explore the relationship of exposure to ultraviolet radiation with the risk of other non-cutaneous cancer sites. These estimates will be derived using Cox proportional hazard’s regression controlling for potential confounders. The study will combine questionnaire and cancer registry data to provide cancer risk estimates associated with different patterns of UVR exposure. Results from the study could provide clarity on the beneficial and detrimental types of UVR exposure for site specific cancer development.

Despite evidence that many cancers are preventable by adherence to a healthy lifestyle (not smoking, consuming alcohol responsibly, engaging in regular physical activity, maintaining a healthy body weight and eating a healthy diet), the prevalence of these modifiable risk factors remains high among Canadians and is strongly socioeconomically patterned. Studying socioeconomic inequalities in relation to cancer risk factors or outcomes is challenging since socioeconomic status (SES) is a complex and multidimensional concept that encompasses many aspects. Existing individual-level SES indices are scarce and dated, and primarily rely on an average score approach using a limited set of indicators (education, income, occupation) rather than newer variable reduction techniques based on an expanded set of SES aspects.

The overarching aim of the proposed study is to construct and validate individual-level SES indices by incorporating a larger set of economic, social and demographic factors.

Our specific objectives are to:

  1. Construct an individual-level SES index based on a standard set of indicators (education, income, occupation) using a traditional average score approach;
  2. Construct an individual-level SES index based on an expanded set of indicators (education, income, occupation, employment status, work schedule, marital status, family structure) using a variable reduction technique;
  3. Validate the derived SES indices by examining their association with smoking: one of the key risk factors for cancer.

The objectives will be addressed in Alberta’s Tomorrow Project (ATP) study, a prospective cohort of 31,072 Albertan adults aged 35-69 years with no prior personal history of cancer other than non-melanoma skin cancer. Data from 26,518 participants that completed the Core Questionnaire will be included in analyses. SES will be based on educational attainment, annual household income adequacy, occupational prestige, employment status, work schedule, marital status and family structure. Data analyses will include construction of an average score SES index using Statistics Canada’s methodology (Objective 1), a data-derived SES index using principal component analysis (Objective 2), and assessment of their association with smoking (pack-years), using regression modeling (Objective 3).

The ATP infrastructure would benefit from a uniform approach to combine multiple indicators into a single SES index and its application in capturing SES inequalities in cancer risk factors and outcomes.

Three in five Canadians are overweight or obese and an even larger percentage may have potentially harmful levels of body fat. Excess body weight is a strong risk factor several chronic conditions and certain types of cancer including postmenopausal breast and colorectal cancer. However, some studies have found a paradoxical inverse relationship between excess body weight and lung cancer such that being classified as overweight or obese actual protects against the development of lung cancer. Two commonly proposed biological mechanisms explaining how excess body weight increases the risk of cancer are: i) excess body weight results in chronic low-level inflammation, which can eventually result in DNA damage and ii) excess body weight results increased blood levels of insulin and insulin-like growth factor-1, which stimulates the growth and production of cells, leading to tumor development. However, the connection between how modifiable lifestyle factors such as body size are linked to inflammatory processes and insulin resistance remain poorly understood.

Starting in 2000, enrolled over 55,000 participants aged 35–69 years were enrolled in Alberta's Tomorrow Project (ATP) - a population-based prospective cohort study. All participants completed questionnaires that collected detailed information on lifestyle factors, socio-demographics, personal and family health history. Some participants also visited a study center where physical measurements and blood samples were collected. A total of 171, 93 and 47 participants who provided a blood sample have been diagnosed with breast, colorectal, and lung cancer, respectively, during the follow-up period. The primary objective of this study is to investigate the relationship between lifestyle factors (measured via questionnaires), inflammation, insulin resistance (measured via blood biomarkers) and subsequent risk of breast, colorectal and lung cancer within ATP. Results generated in this project will improve our understanding of site-specific cancer risk factors and may lead to improved prevention strategies that promote weight management and identify high-risk individuals.

Breast cancer continues to be the most commonly diagnosed cancer among Canadian women. Despite a decrease in the number of breast cancer diagnoses in older women in the past 25 years, diagnoses among women under the age of 50 have increased. The Canadian Cancer Society estimates that 17% of newly diagnosed breast cancer cases will be in women under the age of 50 in 2017. Young women diagnosed with breast cancer tend to have poorer survival because they are not routinely screened, thus they are often diagnosed with advanced-stage cancer. Breast cancer in older women has been studied extensively, but comparatively, little is known about the risk factors for young-onset breast cancer. Inherited genetic mutations play a role, but generally, only account for 5-10% of young-onset cases, suggesting lifestyle or environmental factors may contribute to the development of young-onset breast cancer. In particular, the role of obesity requires clarification since recent studies have suggested a decreased breast cancer risk associated with obesity in younger women.

The Canadian Partnership for Tomorrow Project (CPTP) is Canada’s largest population cohort study that was developed to explore relationships between lifestyle, genetic, and environmental factors and chronic disease outcomes. In this project, we will use data from three sub-cohorts in CPTP (BC Generations Project, Alberta’s Tomorrow Project and Ontario Health Study) to examine the risk factors of young-onset breast cancers in those less than 50 years of age. Results generated in this project will improve our understanding of breast cancer risk factors in younger women, leading to improved prevention strategies in young women at elevated risk of breast cancer.

Rare cancers make up approximately 25-35% of new cancer cases in Canada annually. However, research on this group of cancers receives little scientific attention and fiscal support, relative to common cancers. Because of this, the magnitude of the societal burden attributable to rare cancers is poorly defined, limiting progress in improving patient outcomes. Analysis of data from the Alberta Tomorrow Project (ATP) will make up a component of a project aiming to identify strategies for improving the efficiency of surveillance and etiologic research on rare cancers in Canada. Analysis of data from the ATP will be used assess the feasibility of using this cohort and the pan-Canadian counterpart, the Canadian Partnership for Tomorrow Project (CPTP), for research assessing risk factors for selected rare cancers. Data from this cohort, linked with cancer diagnosis data compiled in the Alberta Cancer Registry (ACR), this project will address the following aims:

  1. Compare self-reported data on cancer diagnoses with data compiled in the ACR to measure the level of agreement between these methods of measuring the occurrence of cancer in the population and subsequently the validity of self-reported cancer diagnosis data;
  2. Estimate the effects of health and lifestyle behaviors and participant characteristics on the risk of developing each of the following cancers: esophageal, stomach and brain.

Worldwide, colorectal cancer is the third most common cancer. Men are more likely to develop colorectal cancer than women. Different environmental, lifestyle and biologic factors may explain this difference. Also, research is uncovering the role of estrogen, a hormone that promotes the development and maintenance of female characteristics, in preventing colorectal cancer in women.

Less is known of the role of hormones in the development of colorectal cancer in men. Similar to the evidence in women, there is support that the proper functioning of sex hormones may prevent colorectal cancer in men. Endocrine disruptors are chemicals that interferes with the proper functioning of sex hormones. We are exposed to these chemicals in the environment and in diet; however, workers in certain sectors are highly exposed to endocrine disruptors.

In this research, we will examine whether exposure to endocrine disruptors in the workplace increases the risk of colorectal cancer. Our research will be based within participants of the Canadian Parternship for Tomorrow Project. This study included men and women who have shared information on their health, lifestyle, environment and behaviours. Our research will include all men and women who were newly diagnosed with colorectal cancer since 2009. For comparison, we will select a sub-group of people, who have not had cancer at the beginning of the study. The interview asked detailed questions on the longest-held job for all participants. Using this information, we will determine whether exposure to endocrine disruptors at the longest held job was probable or not. We will compare the number of colorectal cancer cases among participants who were probably exposed to endocrine disruptors to those who were never exposed. This study offers a valuable opportunity to examine, in a short time frame and at low cost, whether endocrine disruptors play an important role in colorectal cancer risk.

We have developed risk prediction models for breast cancer using the UK Biobank female cohort and ovarian cancer using the Ovarian Cancer Association Consortium (OCAC). These risk models are based on Caucasian populations.

The models aim to address risk factors including genetic and lifestyle factors. The latter has public health implications in that these factors can be modified leading to cancer prevention. To develop the models, we applied statistical approach and carried out essential checks to ensure the validity of the models. The models yield reasonable accuracy (ability to discriminate between those with and those without the outcome) and are well calibrated (the agreement between observed outcomes and predictions). We are now seeking data from the Alberta’s Tomorrow Project (ATP) female cohort to test if our models obtain similar accuracy and good level agreement between females with and without outcome of interest.

2017 Approved Projects

Differences in individual, health system and clinical factors, such as awareness of cancer, health habits, diagnostic delay, screening, stage, comorbidity and access to care, are all potential explanations of differences observed within Canada in cancer survival and mortality. Predictive models designed to support decision making following cancer diagnosis often account for diverse patient risk factors. However, few tools for predicting cancer outcomes include information that may influence probability of early detection such as co-morbidity, family history, lifestyle risk factors, access to screening, or occupational history.

This project will explore patient and system factors associated with stage of cancer at diagnosis, using data from Alberta’s Tomorrow Project (ATP). Nearly 2500 ATP participants have been diagnosed with cancer since joining ATP. Linkage of ATP data with administrative databases will provide screening information at multiple time points, as well as diagnostic information.

The specific aims are to:

  1. Develop multivariable regression models using ordinal logistic regression to identify independent and synergistic factors associated with cancer stage at diagnosis;
  2. Explore reductions in stage at diagnosis that may be possible by modifying these identified factors (individual and health care system) in simulation studies; and
  3. Validate the models using data from the BC Generations Project.

The comprehensive modeling of factors associated with incident cancers in ATP will provide information simply not attainable in other provincial databases. Validation of Alberta results with B.C. data will ensure the methodology performs as expected, while providing additional support for translating the findings into cancer screening practices in Alberta and beyond. Using a simplistic framework of delayed stage at diagnosis, we will identify factors that can be used by screening programs to identify individuals who may benefit from individualized screening practices or from targeted prevention messages, thereby increasing the proportion of cases diagnosed at earlier stages.

A growing body of literature exists exploring the relationship between lifestyle factors, such as diet and exercise, and cancer risk. Fruit and vegetable consumption may be protective against the development of oral cavity, pharynx, larynx, esophagus, stomach and lung (fruit only) cancer. A recent study suggested that approximately 2% of new cancer cases in Alberta in 2010, representing around 290 cases, could be attributed to insufficient fruit and vegetable consumption1. Physical activity has also been linked to decreased risk of cancer. A meta-analysis found that cancer risk was reduced in people who engaged in the highest levels of leisure time physical activity2. Despite growing research into how diet and physical activity influence the development of cancer, limited research exists as to whether lifestyle factors prior to a cancer diagnosis may influence treatment outcomes after a cancer diagnosis.

Some research exists as to how diet and exercise affect cancer recurrence. However, the majority of these studies examined diet and exercise near or after the diagnosis of cancer. One retrospective study showed that higher levels of physical activity one year prior to diagnosis with breast cancer resulted in slightly better hazard ratios for overall survival. In addition, physical activity following diagnosis was found to slow progression of cancer and reduce the risk of secondary life threatening disease. It is plausible that in addition to reducing primary cancer risk, a history of exercise long before a cancer diagnosis could potentially lead to improved disease outcomes in patients newly diagnosed with cancer.

Through linking data from Alberta’s Tomorrow Project (ATP) with data from the Cancer Measurement Outcomes Research and Evaluation (C-MORE) group in Alberta, the relationship between lifestyle factors in the years prior to diagnosis and outcomes following treatment can be assessed.

Lung cancer is the leading cause of cancer death in Canada and around the world. Early detection and treatment of lung cancer through screening seem to be the most promising strategy to reduce lung cancer mortality. The Canadian Task Force on Preventative Health Care (CTF) has recently published recommendations in favour of low-dose computed tomography (LDCT) screening for high risk individuals as defined in the National Lung Screening Trial (NLST) (i.e., ever smokers aged 55 to 74 years, ≥30 pack-years of smoking and <15 years since quitting). Nevertheless, a risk prediction model based on Prostate, Lung, Colorectal and Ovarian Cancer Screening (PLCO) data has been developed and suggested that use of an accurate risk prediction model for selecting individual for lung cancer screening is more efficient than applying the NLST criteria. Therefore, we aim to validate this lung cancer risk prediction model and compare its performance vs. NLST criteria in a Canadian population to inform optimal inclusion criteria for a clinical screening program using Alberta’s Tomorrow Project (ATP) dataset.

Background: Epidemiological findings suggest that red and processed meat consumption is positively related to cancer risk and there is an important socioeconomic gradient in following a healthy diet among Canadians. Researchers have only recently begun to examine the presence of interactions between different food items and their relation to cancer risk. These observations underscore the importance of research aimed at understanding the role of simultaneous exposure to the key food items recommended for cancer prevention in order to optimize future prevention efforts to reduce cancer burden. Elucidating how socioeconomic status (SES) confers risk for cancer will inform inequalities in cancer incidence.

Study Aim: The aim of the proposed study is to examine the co-occurrence of adverse intakes of red and processed meat, vegetables and fruit, and fiber, and its impact on cancer incidence and SES inequalities in cancer risk in a large prospective cohort study.

Methods: This study will utilize data from Alberta’s Tomorrow Project a large ongoing prospective cohort of 55,000 Albertan adults aged 35-69. Dietary intake of red and processed meat, vegetables and fruit, and fiber was assessed through a past-year food frequency questionnaire. We will construct a measure of co-occurrence by summing different consumption levels (e.g., high/medium/low) of the estimated mean daily intakes of nutrients and food group servings, including the number of servings or daily intake for red and processed meat, vegetables and fruit, and fiber. Measures of socioeconomic status will be based on education level, annual household income and working status. Cancer incidence will be determined using cancer registry linkage data. Data analyses will be adjusted for gender, physical activity, weight status, current and past smoking, alcohol use, cancer screening tests, first degree family history of cancer and chronic disease, and personal history of chronic disease.

Significance: Results will provide new knowledge about the potential synergies of dietary intakes of red and processed meat, vegetables and fruit, and fiber for the development of cancer risk, and gain insights into SES disparities in this relationship.

Being physically active have been shown to reduce the risk of some cancers. There are different types of physical activity, including activity at work and recreational activities. Participation in recreational activities has been shown to reduce lung cancer risk. However, the role of physical activity at work in affecting the development of lung cancer is not well-established. In fact, some studies have found that people who have physically demanding jobs also have a higher risk of lung cancer. As people spend many hours at work and some jobs are very physically demanding, new studies are needed to fully understand the role of physical activity at work on lung cancer development. In this research, we will examine how lung cancer risk is associated with physical activity levels at work. Our research will be based on the Canadian Partnership for Tomorrow Project (CPTP). Our research will include all men and women who were newly diagnosed with lung cancer since CPTP began. For comparison, we will also select a subgroup of people, who did not have a cancer at the beginning of the study. The interview asked detailed questions on the longest-held job for all participants. Using this information, we will compare activity levels in the longest-held job between those who were diagnosed with lung cancer and those who remained cancer-free. This study offers a valuable opportunity to examine, in a short time frame and at low cost, whether physical activity at work plays an important role in lung cancer development. The role of physical activity (PA) at work in affecting the development of lung cancer is not well established. As people spend many hours at work and some jobs are very physically demanding, new studies are needed to fully understand the role of PA at work on lung cancer development. AIMS: To investigate the relationship between occupational PA levels and lung cancer risk. We will also explore potential effect modification by occupational lung carcinogens.

METHODOLOGY: This research will be conducted among individuals enrolled in the Canadian Partnership for Tomorrow Project (CPTP) using a case-cohort design. Cases will include all participants with an incident diagnosis of lung cancer during a follow-up period from baseline to 2016 (estimated N=1280). A sub-cohort of 5120 individuals will be randomly sampled from the entire CPTP cohort at baseline. All participants with a history of cancer (other than non-melanoma skin cancer) at baseline will be excluded. At baseline, participants of CPTP provided detailed information on their longest-held job, including job title, industry, and age at which the job started/ended. To assign metabolic equivalent of tasks (MET) to the longest-held job, we will use data generated by our team on the energy expenditures associated with almost 3600 job titles. Exposure to occupational lung carcinogen in the longest-held job will be determined by linkage with the Canadian job exposure matrix. A weighted Cox proportional hazards regression model will be used to estimate adjusted hazard ratios and 95% confidence intervals for the associations between occupational PA in the longest-held job and lung cancer risk, separately for men and women. We will also explore analyses considering the main histological types of lung cancer. Potential effect modification by exposure to occupational carcinogens will be analyzed through the inclusion of specified multiplicative interactions.

2016 Approved Projects

Individuals of South Asian origin (from the following countries: India, Pakistan, Bangladesh, Sri Lanka and Nepal) represent the majority of the immigrant population in Canada. Acculturation of dietary practices and adaptation of locally available foods in the diets may be challenging for many new immigrants. Further, South Asians are at risk of early onset cardio vascular diseases (CVD), pre-diabetes and type 2 diabetes (T2D). Lifestyle choices and dietary intake are modifiable risk factors that can alter the risk of developing chronic diseases, however there is limited data examining dietary practices of South Asian in North American or Canadian contest. Thus, the objective of the present study is to describe the dietary patterns among people of South Asian origin and their risk for developing metabolic syndrome and chronic diseases such as CVD and T2D. We will conduct a cross-sectional investigation of data collected from South Asians participating in the “Alberta Tomorrow Project” (ATP). Assuming that ATP recruitment was representative of the Alberta population, and based on South Asians comprising 4% of the Canadian population, we estimate ~1000 South Asians would have participated in this study. The study aims for this project are as follows: 1. Assess dietary intake and alcohol consumption of South Asian population. 2. Compare dietary intake of South Asian population to the Healthy Eating Index score as a means of assessing adherence to dietary recommendations made in “Eating Well with Canada’s Food Guide”. 3. Compare dietary intake of South Asian population to the Alberta Diet Score as a means of assessing acculturation to a dietary pattern typical of the Prairie Provinces. 4. Assess metabolic disease risk based on the eating patterns of South Asian population. Results from this study will help inform and prepare targeted intervention programs to improve dietary and lifestyle choices within these communities.

Physical activity has well-established links in the prevention and management of a number of chronic conditions, including cancer and in particular, cancers of the breast, colon and endometrium. Reductions in risk by as much as 20-40%for certain chronic diseases have been shown in adults with the greatest level of physical activity compared to sedentary individuals. Increased sedentary behavior has also been strongly associated with the risk of many chronic health conditions, especially diabetes, obesity and cancer. This relation has been found to be independent of physical activity and is strongest for colon, breast and bladder cancers. Lastly, excess body weight/obesity has been associated with cancer risk, particularly for cancers of the endometrium, gallbladder and kidney in women and cancers of the esophagus, colon and thyroid in men. The objectives of the proposed study are to use data collected by the Alberta’s Tomorrow Project (ATP) from over 50,000 participants to: (1) derive cancer risk estimates associated with physical activity (intensity, frequency and duration), sedentary behaviors, excessive body weight/obesity and stress; (2) determine how additional covariates, such as sociodemographic characteristics, influence the prevalence of physical activity, sedentary behaviors, obesity, stress, tobacco smoking and adverse health outcomes, especially cancer; and (3) assess the joint effects of exposures, as well as the mediation/relationships between exposures. These estimates will be derived using Cox regression, path analysis and structural equation modelling. The proposed study will combine questionnaire and cancer registry data provided by ATP participants to provide accurate and reportable estimates of physical activity, sedentary behavior and excess weight/obesity as they relate to cancer risk outcomes in the adult Albertan population. Results from this study will support the development of approaches to better assess the relationship between cancer risk and these lifestyle factors in human populations.

Between 2000 and 2015, Alberta’s Tomorrow Project (ATP) enrolled ~50,000 adults aged 35-69y into a prospective cohort established to support future studies in cancer and chronic disease etiology.

In Phase I (2000-2008), participants completed general health and lifestyle, diet and physical activity questionnaires, and gave consent for linkage with administrative databases. Pilot studies investigating the feasibility of blood collection from a geographically dispersed cohort were undertaken. A manuscript describing this period is currently in press (Robson et al. 2016).

In Fall 2007, the Canadian Partnership Against Cancer called for a proposal to develop a cohort of up to 300,000 adults across Canada. At that time, several cohorts (such as ATP) were already underway, and thus it was decided that a pan-Canadian cohort (called the Canadian Partnership for Tomorrow Project, CPTP) could be created by leveraging existing infrastructure and additional funding sources. The joining of ATP to the CPTP initiative is described as Phase II.

For Phase II of ATP (2009-2015), recruitment to the CPTP protocol in Alberta was accomplished in two ways. First, existing ‘active’ Alberta’s Tomorrow Project participants enrolled between 2000 and 2009 (n=31,213) were invited to re-consent to the pan-Canadian protocol; 15,872 (51%) accepted, and, of these, 10,212 people (63% women) attended a study centre to provide biospecimens for banking. The second approach was to recruit new participants using various strategies; 24,321 additional participants were enrolled, and 84% of those attended a study centre for physical measurements and biospecimen donation.

The purpose of the present study is to describe methods for recruitment and to characterize the participants who were enrolled in Phase II. We will summarize and describe Phase II participants based on sociodemographic characteristics and health-related characteristics. In addition, we will compare and contrast ATP participants who consented and those who chose not to consent to the CPTP protocol.

Tobacco use and exposure have notable implications for disease, disability and death (WHO, 2008). Strong and consistent epidemiologic evidence exists that tobacco smoking and exposure causes cancers and other chronic diseases (Jha et al., 2009). Additionally, changes to tobacco legislation have been shown to impact use and exposure prevalence at a population level and may have implications for disease trajectories (Who, 2008).

The proportion of incident cancer cases and chronic diseases attributable to active and passive tobacco exposure in Alberta has been previously examined using data from the 2000-2007 Canadian Community Health Survey (CCHS) (Poirier et al., 2015). However, CCHS is limited in its ability to examine changes in the same sample over time. Alberta’s Tomorrow Project (ATP) is in a unique capacity to overcome this limitation.

The Alberta provincial government introduced the Tobacco Reduction Act on January 1, 2008 which comprehensively banned smoking in all workplaces and public places (including within a five meter range of any air intake, door, or window) throughout the province (Alberta Provincial Government, 2007). Moreover, it prohibited the sale of tobacco products in all post-secondary institutions, healthcare facilities, and stores containing pharmacies. The purpose of these legislative changes was to influence the sale and use of tobacco products, and consequently, exposure. There is a dearth of studies to date that have deliniated the impact of legislative changes on smoking use and exposure prevalence within the same individuals over time.

Alberta’s Tomorrow Project (ATP) captured smoking status and second hand smoke exposure prevalence in participants at enrollment (2000-2008) and follow-up (2009-2015). This study is in a unique capacity to evaluate the possible impact and implications of 2008 tobacco legislative changes for both active and passive tobacco exposure as well as chronic disease occurrence over a period of time within the same sample of individuals in the province of Alberta, Canada.

This project will estimate the prevalence of active (current or former smoker) and passive (second-hand smoke) tobacco exposure in Albertan adults (aged 35-69 years old) enrolled in phase I of the ATP cohort. Changes on tobacco use, exposure, chronic disease occurrence and quitting behaviors have been captured at enrollment and follow-up from self-report questionnaires. The data will be used to determine the potential impact of the 2008 legislation on tobacco use and exposure prevalence at a population health level, much like a natural intervention, in order to determine possible implications on chronic disease occurrence and trajectory. Quitting behaviours at the 2008 follow-up will also be used to assess cessation intentions and resulting changes in current users at follow-up. Finally, we will identify the socio-demographic factors associated with these exposures and evaluate how these rates change over time within individuals.

The objectives of this study are to determine the:

  1. prevalence of and changes in smoking use and second-hand smoke exposure prevalence of ATP cohort participants before (2000-2007) and after (2009-2015) the 2008 tobacco legislative changes took effect in Alberta
  2. prevalence of intentions to quit tobacco smoking at Survey 2008, rationale for quitting and smoking status outcome at follow-up
  3. change in chronic disease incidence from enrollment to follow-up and relating these to tobacco use and exposure

To our knowledge, these will be one of the first estimates within the same sample of individuals to determine the possible impact and implications of 2008 tobacco legislative changes for both active and passive tobacco exposure as well as chronic disease in the province of Alberta, Canada.

It is well established that dietary measurements are prone to error. Accounting for misreporting error (either underreporting or overreporting both energy intake and food items) is an important step towards understanding and clarifying the potential role diet plays in disease outcomes. The gold standard for assessing misreporting is the measurement of energy balance using doubly labeled water. However, the high expense of this technique makes it unrealistic for use in large cohorts; therefore, alternative statistical methods are available to identify individuals who misreport. The Goldberg method identifies misreporters based on cut-offs between the ratio of energy intake and basal metabolic rate compared to physical activity level (PAL). However, the PAL needs to be assumed in order to use the Goldberg method. In contrast, the updated McCrory method only uses PAL to select the appropriate prediction equation to calculate the estimated energy requirement (EER). The EER is then compared to energy intake as a cut-off in the McCrory method. Depending on which method is used, there could be a different group of individuals identified.

Additionally, the choice of misreporting method could have implications for dietary pattern analysis. The associations between dietary patterns identified and disease outcomes such as cancer could be vastly different whether or not inaccurate data is included in the analysis. Dietary components such as glycemic load are likely to be influenced by the inclusion of misreported data in the analysis. Therefore, associations between glycemic load and cancer risk may have different results if misreported data is present. This project will address the following objectives:

  1. Identify energy intake misreporters in ATP using a comparison of the Goldberg and updated McCrory methods.
  2. Determine the influence of misreported energy intake on dietary patterns identified in ATP.
  3. Determine the relationship between dietary patterns, glycemic load, and both the risk of overall cancer as well as particular sites including breast and colorectal.

Background: Screening for cancer is a secondary prevention strategy that relies on early detection to identify and halt the pathological development of disease in asymptomatic individuals who are at risk of disease. Religion and spirituality (R/S) may encourage or discourage people from undergoing screening for disease, while perceived susceptibility (PS) – whether an individual feels they are personally vulnerable to a health-related condition or disease – has been shown to be associated with cancer screening uptake.

Overall Objective: We propose to use data from the Health and Lifestyle Questionnaire (HLQ), Survey 2004, Survey 2008, Update Health and Lifestyle Questionnaire (UHLQ), and Core Questionnaire (Core) from the Alberta Tomorrow Project (ATP) to address the following research questions:

  1. What is the association between R/S at baseline and the incidence of sigmoidoscopy, colonoscopy, prostate specific antigen (PSA), Pap, and mammography screening tests in the ATP?
  2. Is PS to developing cervical, breast, prostate, and colorectal cancer associated with the incidence of PSA, Pap, mammography, sigmoidoscopy, and colonoscopy screening tests in ATP? Does an individual’s PS of developing cancer differ across diseases? Does an individual’s incidence of screening differ between screening tests?

Methods: We will include ATP participants of any age who report being free of chronic conditions at their baseline interviews and who have at least one follow-up interview. We will explore the data descriptively using histograms and bar charts. We will summarize normally distributed continuous variables as means and standard deviations, non-normally-distributed continuous variables as medians and interquartile ranges, and categorical variables as frequencies (n/%). To examine the association between the exposure variables (R/S or PS) and incident screening at follow-up, we will build a series of multivariable logistic regression models for each of the screening tests of interest.

Lung cancer is the primary cause of cancer mortality. Its presentation at late stages is one of the main factors responsible for the overall poor survival of patients with this disease. Approximately 75% of non-small cell lung cancer (NSCLC) cases are presented at an incurable stage. Micro-ribonucleic acids (miRNAs), non-protein-coding RNA strands, are promising candidates for cancer biomarkers due to them being expressed in a tissue-specific manner. Dysregulation of miRNAs can lead to carcinogenesis as they may function as tumor suppressors or promoters. Using miRNAs would allow us to screen for cancer using body fluid-based tests that are minimally-invasive, relatively low-cost and easily repeatable. There is a high false positive rate with CT screening for lung cancer, and this leads to patient anxiety and unnecessary tests. Circulating biomarkers are attractive for cancer screening since they are body fluid-based tests that are minimally-invasive, relatively low-cost and easily repeatable. In our previous work a miRNA panel was developed and has demonstrated good sensitivity and specificity in early stage lung cancer studies when measured in sputum and bronchial washing with RT-PCR and cluster analysis of miRNA profiling. RT-PCR is used as a standard method to detect miRNA. We hypothesize that miRNA profiling collected from blood plasma can be used for future detection of early stage NSCLC. To do this, we propose a case control study of clinical stage I/II NSCLC, matched with healthy controls. Inclusion of 70 cases and 110 controls matched for age, gender, and smoking history will allow statistical significance, which is recommended for such studies. We also want to characterize the hypothesis that after surgical resection of the cancer tissue, miRNA levels will change. To do this, we will compare miRNA levels from plasma before and after surgery. This can lead to development of future screening for recurrence of cancer.

2015 Approved Projects

Over the past two decades, several organizations have published series of recommendations and guidelines that provide strategies for cancer risk reduction based on modifiable behaviors and lifestyle factors. Although fine details of the recommendations differ, many focus on the broad themes of achieving and maintaining a body size within the normal range for body mass index (BMI), being physically active, consuming low amounts of alcohol (if consumed at all), avoiding exposure to tobacco, consuming diets that are predominantly plant-based and/or relatively high in fruits and vegetables, and participating in screening programs. Similar types of recommendations exist for reducing risks of cardiovascular disease and type II diabetes.

Currently there is a dearth of comprehensive population-based prevalence data for modifiable cancer and chronic disease risk factors in Alberta, and across Canada as a whole. We propose to describe the prevalence of a series of risk factors (physical inactivity, overweight and obesity, diet related risk factors, alcohol use, and tobacco use) reported by adults enrolled in Alberta’s Tomorrow Project (n=31,157). We will also describe the extent to which participants comply with cancer screening guidelines.

Alberta’s Tomorrow Project used the method of Random Digit Dialing to recruit approximately 30,000 participants across Alberta between 2000-2009. Only people within the ages of 35 and 69 years with no history of cancer were recruited.

The study will provide the descriptive analyses of exposure distribution of cancer and chronic disease risk factors in the ATP population upon enrollment in the cohort. Data concerning time and energy expended in domains of recreation, transportation, household and occupation, the distribution of BMI, waist circumference and waist/hip ratios reported by participants, reported intakes of vegetables, fruits, whole grains, red meat, energy and macronutrients (including sources) and self-reported alcohol and tobacco exposure will be described by sex, age category and other demographic variables.

Analyses of these data will be the first step in helping identify priority areas for the development and implementation of comprehensive cancer and chronic disease risk reduction strategies in Alberta, and potentially across Canada. They may also help inform other projects that aim to calculate up to date population attributable risks/fractions for cancer and chronic disease associated with the prevalence of modifiable risk factors.

The aim of the current study is to identify breast cancer susceptibility alleles in populations. Breast cancer prediction models have used single nucleotide polymorphisms or SNPs and currently also use copy number variations (CNVs). The true test of the models is to assess for positive predictive value by comparing any potential “outliers” from the controls who may have been diagnosed with breast cancer since their initial enrolment in Alberta’s Tomorrow Project (ATP). Currently, the models simply show in a confusion matrix, cases and controls that are not assigned to proper bins. Access to the refined data from ATP will help to improvise the models. True applicability of the findings rests on improvising the models so that they will have selectivity and specificity for the potential population screening to identify those at risk for breast cancer, long before the actual diagnoses; thus enabling prophylactic interventional modalities to reduce the burden of disease for individuals and the societal burden in terms of health care dollars.

2014 Approved Projects

Limited research has focused on estimating population attributable fractions/risks (PARs) for modifiable risk factors and cancer in Alberta. Information concerning the fraction of cancer attributable to individual risk factors is essential for both developing and implementing population-based cancer prevention strategies.

The objectives of this project are to: 1) estimate the prevalence of exposures to modifiable risk factors consistently associated with cancer for the Alberta adult population; and 2) estimate the number of incident cases of cancer per year attributable to these factors among Albertans.

Three types of data are required for the estimation of PARs including the magnitude of the risk association between individual exposures and cancer sites, estimates of the population prevalence of individual exposures, and the site specific cancer incidence data. Estimates of risk for each exposure and cancer site of interest will be extracted from a review of reports from international collaborative groups/panels and the current published peer-reviewed literature in PubMed. Data on the prevalence of individual exposures of interest will be obtained through: 1) results from Statistics Canada surveys; 2) publicly available government databases; 3)published peer-reviewed literature; and 4)consultation with relevant experts. Data on cancer incidence in 2012 will be acquired from the Alberta Cancer Registry.

The proportion of cancers at a given cancer site that can be attributed to an individual exposure, will primarily be estimated for both Alberta as a whole and for individual Alberta Health Services zones using the formula given by Levin: PAR = (Pe x (RR-1))/(1 – (Pe x (RR-1))). Here Pe represents the population prevalence of a given exposure and RR represents the relative risk of cancer at a specified site for the given exposure.

These estimates will provide a greater understanding about the main causes of cancer in Alberta and will be useful in informing future cancer prevention efforts.

2013 Approved Projects

Anthropometric measurements are used as estimates of excess adiposity and are routinely used in epidemiological studies. Excess adipose tissue is associated with an increased risk of cardiovascular diseases (CVD), hypertension, diabetes and some cancers. Individuals who are overweight or obese have a higher chance of disease risk and even premature death. There exists gender differences in the performance of anthropometric measurements in assessing adiposity. These differences in measurement performance can directly impact the assessment of obesity related disease risk and prevalence in men and women.

The purpose of the project is to examine the performance of various anthropometric measures to assess adiposity and to determine if these results are consistent in both men and women. Specific aims are: i) To describe the consistency with which various measures (BMI, BAI, waist circumference, hip circumference, waist to hip ratio, and waist to height ratio) estimate the prevalence of excess adiposity, ii) To estimate the relation between these measurements (BMI, BAI, waist circumference, hip circumference, waist to hip ratio, and waist to height ratio) and self-reported hypertension, and iii) To determine if there are gender differences in this relation.

A descriptive study approach of self-reported data from approximately 30,000 participants who have completed the Health and Lifestyle Questionnaire, along with the self- reported physical measures will be analyzed using SAS (version 9.1). The various anthropometric measures will be compared across different BMI categories and stratified by gender. The correlation between will also be studied and presented in a correlation matrix. The relation between anthropometric measures and high blood pressure will be studied using logistic regression.

Currently, the PSA test helps to identify men that are likely to have prostate cancer. However, infection, trauma, and benign prostatic hyperplasia (BPH) are all causes of elevated serum PSA, significantly confounding PSA as a cancer biomarker. An improved test could significantly decrease the number of unnecessary biopsies. The present study aims to develop, validate and translate novel tools to improve prostate cancer testing, to determine the aggressiveness of prostate cancer and to improve our prediction of the onset of metastasis in prostate cancer patients. This study will also help us to identify prognostic biomarkers to differentiate more dangerous vs. less dangerous prostate cancer. This important information could help patients and their physicians choose treatment options for an improved outcome and better quality of life.

This will be a study of biofluid samples from prostate cancer patients that have donated their specimens to different biobanks in North America and Australia to evaluate the utility of novel biomarkers to diagnose and predict biochemical recurrence and-or metastasis in patients with prostate cancer. Associated clinical data related to diagnosis, treatment, outcome will be used to associate with results from the research tests. Samples from subjects without prostate cancer are required to serve as controls.

To achieve this, our team will focus on the validation of Cancer Microparticle (CMP)-based tests to diagnose prostate cancer, to predict biochemical recurrence and/or metastasis, and to identify novel markers for prostate cancer. For these studies, plasma, urine and/or semen samples from patients with confirmed prostate cancer and normal controls will be utilized first in retrospective analyses, using biospecimens from different centres across North America and Australia. Later, when APCaRI biobank is established, we will also use prospectively collected biospecimens from prostate cancer patients that donate their samples.

The Alberta Inflammatory Bowel Disease (IBD) Consortium is a team of clinicians and scientists performing large-scale clinical outcome and pathogenetic studies in IBD – particularly focusing on gene, microbe, and environment interactions. The goal of the Consortium is to generate new knowledge through research that will assist in our understanding of the determinants and causes of IBD. With an already established framework of patient recruitment and sample analysis, our attention turns to retrospective patient cohorts to help find genetic, environmental, microbial, and serological factors that contribute to Crohn’s disease (CD) and ulcerative colitis (UC). In this proposal, we will identify Albertans living with IBD and focus on identifying gene-environment-microbe-serology interactions as predictors of disease phenotype, prognosis, and drug response in patients with IBD.

The results of such studies have the potential for primary, secondary, and tertiary prevention of IBD. This will not only better the quality of life of those who are susceptible to IBD and the 15,000 Albertans living with chronic IBD, but it will generate relief to Alberta Health Services as early detection and targeted intervention can alleviate much of the pressure on the health care system. By identifying gene-environment interactions in IBD, steps can be taken to prevent initial development of IBD and reduce morbidity by educating the public of risk factors, implementing screening programs for high-risk populations, and providing prompt early diagnosis and treatment.

Hypothesis: WCRF and the AICR published guidelines on food and nutrition, physical activity, body composition and other modifiable risk factors that may affect the risk of developing cancer and other chronic diseases. We hypothesized that increased overall adherence to these cancer-specific recommendations were associated with a reduced subsequent incidence of cancer. Objective: To estimate the association between Tomorrow Project participants’ adherence to cancer prevention guidelines, as recommended by WCRF and AICR, and the subsequent incidence of cancer observed in the Tomorrow Project cohort. Methodology: The project will involve analysis of data collected from participants in Alberta’s Tomorrow Project. The baseline data (from three baseline questionnaires: Health and Lifestyle Questionnaire (HLQ), Diet History Questionnaire (DHQ) and Past Year Total Physical Activity Questionnaire (PYTPAQ)) were collected over the span of 9 years from 2001 to 2009. Cancer diagnoses in the follow up period will be obtained via a combination of participants’ self report and linkage with the data from the Alberta Cancer Registry.

The final study sample will exclude the following participants: participants who were recruited as ‘second in household’ in the first recruitment wave, participants outside the 35-69 year age range at the time of completing the HLQ, pregnant women, participants with a body mass index (BMI) <18.5kg/m2, participants who reported having history of cancer prior to enrolment, participants not living in Alberta at the time of enrolment, participants who reported implausible energy intakes, and participants with extreme dietary energy intake or total energy expenditure (using the interquartile range method). The project will involve manipulation of the HLQ, DHQ and PYTPAQ datasets to create variables according to the cancer prevention guidelines. Preparation of the datasets and statistical analyses (e.g. descriptive statistics, chi-square tests, logistic regression models, and Cox proportional hazards model) will be conducted at Holy Cross (Calgary) by the Statistical Associate using the SAS software.

2012 Approved Projects

Cancer screening increases the chance of survival and reduces morbidity associated with certain cancers. This study aims to determine the extent of adherence of Alberta Tomorrow Project participants to breast, colorectal, cervix, and prostate cancer screening test guidelines and to identify any patterns of utilization to help developing strategies to improve participation rates. This project will involve analysis of the baseline data from the Health and Lifestyle Questionnaire (HLQ) collected between 2000 and 2009 and Survey 2008, a follow up survey collected between 2008 and 2009. All data is based on self-reported screening status included in HLQ and Survey 2008.

Participants diagnosed with breast, cervix, colorectal or prostate cancer between completing the HLQ and Survey 2008 will be excluded from the analysis of screening patterns at Survey 2008. Utilizing screening tests for each site will be classified as follows: Pap test: within 1 year; 2 to 3 years; more than 3 years; or never screened. Mammography: within 2 years; more than 2 years; or never screened. Fecal Occult Blood Test: within 2 years; more than 2 years; or never screened. Sigmoidoscopy and colonoscopy: within 5 years; never or not within 5 years (on HLQ) and on Survey 2008, within 5 years; or not within 5 years for sigmoidoscopy; and within 10 years; never or not within 10 years for colonoscopy. Overall screening status for colorectal cancer will be determined by combining screening using FOBT and/or endoscopy with up-to-date defined as any of: FOBT within the past 2 years; sigmoidoscopy within the past 5 years; colonoscopy within the past 5 (HLQ) or 10 (Survey 2008) years. PSA: within 2 years; more than 2 years; or never screened. Reason for screening categories classified as screening; family history; or indication.

Patterns of screening for each site will be described based on screening status at HLQ and Survey 2008. This data analysis is descriptive and exploratory and the final categories will depend on the patterns observed in the data. Statistical analysis (e.g. descriptive statistics, chi-square tests, logistic regression models) will be conducted using the SAS software.

Obesity is of major public health concern in Canada. The percentage of Canadians who are overweight or obese has risen dramatically in recent years, mirroring a worldwide phenomenon. Worldwide it is estimated that 25% of all cancer cases are caused by obesity. Specifically, there is convincing evidence that overweight and obesity increase the risk for other chronic diseases, including type 2 diabetes, cardiovascular disease, hypertension and stroke and cancers of the endometrium, breast, colon, esophagus and kidney. The cause of this rapid increase in obesity has been attributed to lifestyle, environmental and cultural factors that have resulted in a shift toward a sedentary lifestyle, with an over consumption of calories and reduced physical activity.

As individuals age there is a tendency to gradually gain weight. This is partially due to increasing age corresponding to a decrease in muscle mass and subsequently metabolism (sarcopenia), lifestyle changes and increasing prevalence of other health conditions that may limit an individual’s ability to exercise. An average annual weight increase of one pound has been commonly reported during middle adulthood. An increase in caloric intake relative to energy expenditure of just 50 to 100 Kcal per day is enough to cause this gradual weight gain. The middle age weight increase may be of importance to cancer prevention as the proportion of the population in the older age categories increases. However, there are relatively few studies which have investigated the factors associated with weight change over time in middle adulthood. To our knowledge there are no studies investigating this topic in Canada. The aim of this study is to investigate weight changes over time associated with increasing age and to explore potential explanatory factors in the Tomorrow Project cohort.