To reduce the incidence and mortality from cancer in British Columbia through a program of innovative cancer research. More specifically, to discover those genetic, environmental and occupational factors and their interactions that define cancer risk and that can inform the development of new strategies for prevention, early detection and treatment.

The overarching theme of this submission is elucidation of the relationship between cancer and the environment. The estimate that 80% of cancers have environmental triggers (Harvard ref) includes factors such as obesity, diet and physical activity levels, which might be considered 'lifestyle factors', nonetheless these factors are modifiable and hence can be considered to be subject to change in individuals' personal environment. Over and above these factors, however, there is no doubt that a substantial proportion of cancers is due to physical, chemical, and workplace exposures.

Recently, advances in molecular biology have opened new windows on individual susceptibility to chronic diseases. Thus it is no longer adequate to attribute disease risk solely to the putative carcinogenic exposures that individuals are subject to. In fact it is clear that exposure and susceptibility work together to determine risk. The interaction between susceptibility and exposure is now thought to be the most fruitful avenue to pursue in exploring the underlying causes of cancer and new avenues for its prevention. Due to its unique strengths, the CCR Research Unit is poised to become a world leader in this important and timely field of investigation.

The Cancer Control Research Program has underway a number of studies designed to examine gene-environment interaction, and this state-of-the-art program is now the principal research sub-theme of this Research Unit.

At the same time that genomics and proteomics have enlarged the scope of research possible on individual susceptibility to chronic disease, another trend has emerged -namely the study of pre-cancerous lesions. Cancer is known to be a disease requiring several steps (Knudson 1971); broadly described as initiation and promotion. Initiation can be broadly defined as the generation of irreversible mutation, in cellular DNA, which are passed on to daughter cells. These cells have undergone the first step in malignant transformation, although at this stage they are far from constituting a frank malignancy. A number of other 'hits' occur, due to exposure to cancer 'promoters' which result in further mutation in the cell. Agents which act as promoters, act over a prolonged period to move the cell or clone of cells toward malignant transformation. Since the process of initiation and promotion may take up to 20 years, there is concern from a treatment point of view about whether the malignant process can be halted at the diagnosis of a frank cancer. From the point of view of etiology, there is also concern-namely that looking at risk factors for frank malignancy may elucidate factors that are not modifiable by public health or other interventions. This has resulted in the development of etiologic programs designed to identify risk factors that predispose to pre-cancerous lesions. Finally, in order to make full use of etiologic information, it must be translated into programs aimed at primary or secondary prevention. In order to do this; trials are necessary to evaluate prevention interventions translated from the etiologic data. The Cancer control Research Program has a number of these trials underway or in the planning stages.

Goals:

The goal of the Cancer Control Research Unit is to leverage the existing program in cancer etiology research into an internationally recognized program of excellence by linking genetic (and serum) biomarker information to our existing high quality program of environmental exposure assessment. The resulting gene-environment studies will position the unit at the forefront of epidemiologic research. Furthermore our program in pre-cancerous lesions and in prevention interventions will allow us to utilize the data gained through our gene-environment studies to lower cancer incidence and mortality in B.C. Build and enhance a research system that sustains vital interdisciplinary connections

Characteristics and uniqueness:

The Cancer Control Research Unit is unique in B.C. in that it is the only group whose mandate is to conduct research in cancer etiology and prevention. The unit has a strong cadre of 8 productive scientists, and has recently formed a strategic alliance with the Michael Smith Genome Sciences Centre. This has allowed us to appoint to our unit as joint faculty members, several world-class genome scientists (Dr. Marco Marra, Dr. Angela Brooks-Wilson). The presence of the BC Cancer Registry, and the Cancer Agency's tumour groups allows us routine access to cancer patients, and a mechanism for communicating new findings and rapidly translating them into prevention and therapeutic initiatives.

Using large population-based studies as a foundation, the unit will continue to improve the infrastructure needed to develop comprehensively documented data and biospecimen resources by cancer site in order to identify new environmental risk factors and susceptibility genes and determine their interaction in cancer causation

1. Biorepository
   Our biospecimen repository consists of cryogenically preserved biological specimens placed in short and long term storage. Cancer sites currently stored include non-Hodgkin's lymphoma, ovarian, prostate, oral, ???? Each specimen is linked to extensive documentation on environmental exposures, lifestyle factor, histological and clinical data. This is the building of a key resource to support gene-environment investigations into the future; enabling us to capitalize on advances in discovery made by this unit and other research groups and to take advantage of unanticipated opportunities.
2. Comprehensive Database of Environmental Exposure Data
3. Cancer Registry
   Case identification, source of population histologic and clinical parameters
4. High Throughput Assays for Human Population Genomic Studies
   Will validate relevant biomarkers and candidate susceptibility genes

The Cancer Control Research Unit began to evolve into a unit positioned for study of gene-environment interaction by incorporating biologic markers into its studies some time ago (when?), however in the last 2 years scientists have initiated several large studies. These include a study of pre-cancerous oral lesions, oral cancer, non-Hodgkin's lymphoma, melanoma and ovarian cancer. Recently CIHR has funded another 4-year study of prostate cancer. These studies have required the hire of a part-time laboratory assistant and the equipping of a blood lab and tissue culture lab. Currently we are borrowing human resources for specimen processing from other research groups. Full evolution of the unit will require both increased lab space and facilities and increased laboratory personnel. The increased lab space and equipment will be taken care of with our move into the new cancer research centre now under construction. This request for infrastructure support will help with the human and other resources required.