Marie-Elise Parent

Quebec Research Program for Prostate Cancer Prevention

Funded by the GRePEC Environment-Cancer Program, a partnership between the Cancer Research Society, the Quebec Government and the Fonds de recherche du Québec-Santé ($4.7M). This vast research program builds on data collected as part of the Case-control study of environmental, occupational, lifestyle factors and genetic susceptibility biomarkers in the etiology of prostate cancer funded by the Canadian Cancer Society Research Institute ($1.9M).

Prostate cancer continues to be the most frequently occurring cancer among Canadian men. Each year, about 24,000 Canadian men are diagnosed with this cancer and 4,100 die from it. Although prostate cancer has a very good prognosis, many cancer survivors will have to cope, as a result of their disease or treatment, with lasting side effects seriously impairing their quality of life. The unfavorable circumstances that follow a diagnosis of prostate cancer clearly highlight the need to find ways to prevent this disease; this, in turn, means identifying modifiable risk factors. Efforts to elucidate the risk factors for prostate cancer have met with little success to date. The only established risk factors are the age, the ancestry and a family history of the disease. The temporal and geographic distributions of prostate cancer provide compelling evidence that its etiology involves environmental influences. Occupational agents and lifestyle represent potential environmental risk factors that are both promising and under-studied. Moreover, susceptibility genes are at the cutting edge of prostate cancer research.

In the context of a population-based case-control study carried out in Montreal, we have recruited 2,000 incident cases of prostate cancer and 2,000 controls from the general population. Interviews have been carried out to explore the role of some 300 substances encountered in the workplace. Other occupational factors under scrutiny include night work and stress at work. Moreover, we are assessing the role of several lifestyle factors for which more evidence needs to be accrued, i.e., physical activity (occupational, household, recreational), sexual habits, lifetime body size and abdominal obesity, baldness patterns, smoking, and alcohol. We are also assessing the role of exposures in the residential environment of study subjects. DNA samples have allowed us to carry out genome-wise association study and we plan to assess the role of relevant genetic polymorphisms (mainly carcinogen metabolizing and hormone-related genes); these may influence susceptibility to prostate cancer either alone, or in combination with occupational or lifestyle risk factors. This research infrastructure, perhaps the largest of its kind in the world, represents a unique and long-range research effort into prostate cancer prevention. Statistical analyses of data are on-going.

Case-control study of occupational risk factors for lung cancer

Funded by the Canadian Institutes of Health Research ($2.3M)

Lung cancer is the most common malignant neoplasm in Canada. Survival is poor and the main hope is to prevent the onset of the disease by identifying causal factors which are amenable to control measures. Cigarette smoking is the single most important cause of lung cancer, but it has proven difficult to eradicate. Since cancer is a multifactorial disease, the prevention of lung cancer may be more effectively achieved by acting on cofactors of smoking. The most promising arena to search for other risk factors is in the occupational environment where some have already been identified, and many others are under suspicion. It is important to assess the nature of the joint effects between occupational carcinogens and smoking (additive, multiplicative, etc.), as this permits an estimate of the potential benefit to be derived from eliminating either factor, and it elucidates the mechanism of carcinogenesis. The objective of this research is to investigate the role of occupational exposures in the etiology of lung cancer, and for each occupational risk factor identified, to evaluate the interaction with smoking.

Eligible subjects were males and females, aged under 76, resident in the Montreal area, and Canadian citizens. Incident cases (n=1,400) were actively ascertained from the 18 largest hospitals in the area. Controls (n=2,200) were age and sex-stratified and selected from electoral lists. The data collection methods were based on an approach that was developed and extensively used by our research group. This includes: (i) probing interviews with study subjects to obtain a detailed description of each of the subject’s jobs as well as information on smoking and other covariates; and (ii) review of each job description by experts in industrial hygiene for the purpose of inferring possible chemical exposures. This expert-based retrospective exposure assessment provides data on possible occupational exposure to each of about 300 substances.

The statistical analysis of this large and complex data set will describe the associations between lung cancer and the various occupational exposures, taking into account the possible confounding effects of other variables, using unconditional logistic regression. Based on these analyses, there will be a number of statistically suggestive associations. The multiple testing context of this study requires us to adopt a very cautious attitude in interpreting results. Helping to tease out false positives from true positives will be one of the objectives of the analysis. For each substance shown to be associated with lung cancer, the joint effects of occupational variables with smoking will be explored.

Case-control study of cellular phone use and risk of tumors of the brain, parotid gland and acoustic nerve: the Montreal component of an international study

Funded by the Canadian Institutes of Health Research ($505k)

The use of cellular telephones and microwave telecommunications has increased exponentially in the past decade and is forecast to become a dominant technology in telecommunications. As the number of users has increased, concern has been voiced concerning possible health effects from exposure to radio-frequency (RF) emitted by cell phones. The WHO-sponsored International Agency for Research on Cancer (IARC) undertook to coordinate a study on this issue. A protocol was developed, and investigators from 13 countries throughout the world, including Canada, signed on to collaborate. The multi-centric nature of the study required the use of a common research protocol that allows the combination of collected data. However, each partner had the responsibility of developing and conducting its own study, taking into account the local constraints but respecting the main study goals.

In brief, for the entire multi-centric study, four series of case-control studies have been carried out. They focus on tumours thought to have the highest exposure to RF from mobile telephones: brain (glioma and meningioma), parotid gland and acoustic nerve. The study population consists of all persons (men and women) aged 30 to 59 who reside in study regions with cell phone networks. The diagnosis of cases, recruited in 2002-2004 across all hospitals belonging to the study regions, was confirmed histologically or radiologically, and the exact location of the tumours was determined. Controls were selected from the general population, using the electoral roll, and were matched for age, sex, and study region. The history of cell phone use and the information on other risk factors was obtained from a questionnaire administered during an in-person, computer-assisted, interview. A sub-study of the validity of information provided on the use of cell phones was carried out, comparing reported information with available records of network operators. Indexes of RF exposure to the target organs (and associated uncertainties) were derived from the information on phone use, network characteristics and re-analyses of dosimetric experiments. With 6,420 cases and 7,658 controls overall, INTERPHONE is the largest analytical epidemiologic study ever conducted on this subject. Initial analyses have been published and additional statistical analyses are underway.

The etiology of brain tumours is not well understood. In addition to assessing radiation exposures from cellular phones and other sources, the Canadian component of the study has added an assessment of occupational exposures using our expert-based approach. This will provide unique new knowledge about the role of chemical exposures in brain cancer development.