Environmental Epidemiology

 

Guzzo Chair in cancer and environment

Jack Siemiatycki

 

Our objective is to bring as much scientific evidence as possible to bear on the identification and characterization of the causes of cancer. This grant supports the nucleus of a team involved in epidemiologic research on environmental and lifestyle causes of cancer. Several large data bases have been established and are being analysed. New opportunities for setting up relevant data collections are being investigated. We are also vigilant about research opportunities that arise because of some unique exposure circumstances or because of legitimate concerns expressed by citizens, government agencies or other groups.

 

Contents:

1. Occupational and selected non-occupational risk factors for lung cancer: analysis of a case-control study in Montréal
2. INTEROCC - Occupational exposure to EMF in different frequency bands and selected chemical exposures in relation to risk of glioma and meningioma
3. SYNERGY - Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer: Montreal Component
4. Occupational and Lifestyle factors in etiology of prostate cancer, and establishing a platform for studying susceptibility biomarkers
5. New survival analytic methods for time-dependent exposures in case-control studies, with applications to cancer
6. To develop and validate multivariable lung cancer incidence and prevalence models.
7. A computer-based tool to help assess health risk posed by exposure to chemicals through the skin
8. GENESIS PRAXY: GENdEr and Sex DetermInantS of Cardiovascular Disease: From Bench to Beyond PRemature Acute Coronary SYndrome.
9. Effect modification of gene-mediated susceptibility to myocardial infarction by sex and other conventional coronary risk factors.
10. Investigating the role of the built environment in the development and maintenance of excess weight in a cohort of children at risk for obesity
11. Gene-environment interaction study of postmenopausal breast cancer

 

Jack Siemiatycki (PI); Parent M.-É., Rousseau M.-C., Abrahamowicz M., Leffondré K., Case B., Krewski D

Canadian Institutes of Health Research (CIHR)

 

A large case-control study of lung cancer was conducted in Montreal between 1996 and 2000. The methodology was built on a ground-breaking multi-cancer study conducted by Jack Siemiatycki earlier in his career. The key innovative aspect involves obtaining a detailed occupational history from all participants which is subsequently evaluated by a team of industrial hygienists and chemists. Their task is to infer likelihood of exposure to a list of nearly 300 chemicals for each study participant for each job held. This grant will allow us to conduct multiple parallel sets of analyses that will elucidate the relationship between lung cancer and hundreds of occupational chemicals and other classes of variables such as alcohol consumption, smoking behaviour home heating, ethnicity and others.

 

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INTEROCC - Occupational exposure to EMF in different frequency bands and selected chemical exposures in relation to risk of glioma and meningioma

 

Elisabeth Cardis (PI); Jack Siemiatycki; Marie-Elise Parent

 

National Institutes of Health (NIH)

 

The current project aims to exploit the information on occupational exposures collected within the INTERPHONE study, a multi-national case-control study of the possible association between use of cellular telephones and cancer risk. It has two specific substantive aims:

(1)   To evaluate the possible association between occupational exposure to EMF in different frequency bands and tumors of the brain and central nervous system (specifically, glioma and meningioma).

(2)   To evaluate the possible association between selected occupational chemical exposures and tumors of the brain and central nervous system (specifically, glioma and meningioma).

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SYNERGY - Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer: Montreal Component

 

Anita Koushik(PI), Jack Siemiatycki; Michel Gérin; Jérôme Lavoué·; Marie-Elise Parent·; Kurt Straif·; Paolo Boffetta·; Ann Olsson

 

German Statutory Accident Insurance (DGUV)

 

At a given job or during their occupational history many workers are exposed to more than just one carcinogen. The synergistic effects of these carcinogens on the development of lung cancer are largely unknown. This gap in knowledge impedes more efficient primary prevention and fair compensation of diseased workers. Within the last decade, several epidemiological studies have been conducted on risk factors for the development of lung cancer. In 2006 funds were obtained to set up the SYNERGY project involving eight European centres and coordinated by the International Agency for Research on Cancer. The data from a Montreal lung cancer study (1,200 cases and 1,400 controls ) will be included in this pooled analysis of European lung cancer studies, to assess the risk of lung cancer in workers exposed to more than one occupational lung carcinogen.

 

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Marie-Elise Parent (PI); Jack Siemiatycki; Mark Goldberg; Chokkalingam A., Aprikian A., Saad F., Karakiewicz P

 

National Cancer Institute of Canada (NCIC)/Canadian Cancer Society

 

Prostate cancer continues to be the most frequently occurring cancer among Canadian men and it is anticipated that its overall incidence will continue to rise. Although prostate cancer is referred to as a cancer with a very good prognosis, many cancer survivors will have to cope, as a result of their disease or treatment, with lasting side effects impairing seriously their quality of life. The unfavourable circumstances following prostate cancer diagnoses therefore clearly highlight the need to find ways to prevent this disease which, in turn, means identifying modifiable risk factors.

Efforts to elucidate the risk factors for prostate cancer have met with little success to date. The descriptive epidemiology provides compelling evidence that its etiology involves environmental influences. Occupational agents and lifestyle represent potential risk factors that are both promising and under-studied. Moreover, susceptibility genes are at the cutting edge of prostate cancer research. In this study, we are exploring, using expert-based exposure assessment, the role of some 100 occupational substances under particular suspicion, including several hormone modulators. In addition, we are assessing the role of several lifestyle characteristics for which more evidence needs to be accrued.

 

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Karen Leffondré (PI); Jack Siemiatycki

 

National Cancer Institute of Canada (NCIC)

 

This project aims to develop new methods of survival analysis for assessing the impact of time-dependent covariates in case-control studies, and to apply them to several real-life date sets.

To develop and validate multivariable lung cancer incidence and prevalence models.

Igor Karp (PI); Jack Siemiatycki

 

National Cancer Institute of Canada (NCIC)

 

Lung cancer is the most common fatal cancer in Canada. Despite the incontrovertibly strong association between tobacco smoking and lung cancer, there is still wide variability in risk among smokers. We are proposing to create a multivariable risk assessment tool that would allow estimation of lung cancer risk as a function of several risk indicators. To this end, we plan to use the data from two case-control studies that have been carried out in Montreal by Dr Jack Siemiatycki. The set of candidate risk indicators (selected from the study database, comprising hundreds of variables) will include those representing tobacco smoking history (both first-hand and environmental), age, sex, occupational exposures (in particular, selected dusts and fumes), history of hay fever and respiratory illnesses (emphysema, chronic bronchitis), and some others. The model development will entail several methodological challenges - notably, the fact that the source database is based on case-control design and that the control series was matched to the case series (according to age and sex); the need for transition to multivariable prevalence function from a corresponding multivariable incidence function. The developed statistical models will be subjected to cross-validation and external validation so as to assess and correct for potential model overfitting. The models' predictive performance will be assessed according to several measures of goodness-of-fit and discriminatory ability. The knowledge derived from this study can be applied to the scientific practice of lung cancer risk assessment, diagnosis, and prevention.

 

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A computer-based tool to help assess health risk posed by exposure to chemicals through the skin

 

Jérôme Lavoué (PI)

 

Agence française de sécurité sanitaire de l'environnement et du travail (AFSSET)

Few tools are available to help occupational health practitioners in assessing potential risk posed by exposure to chemicals through the skin. The 'skin notation' system, currently proposed by many organizations that set occupational exposure limits, simply flag chemicals with a potential for skin absorption and subsequent toxic effects. The rationale behind the attribution of skin notations has been assessed as often vague or based on variable information. This project aims at creating a computer-based tool providing in a transparent way all relevant information about toxicity and potential for cutaneous absorption. It will also include a risk index based on estimation of the percutaneous absorption rate with QSAR models and uncertainty analysis using Monte Carlo methods.

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GENESIS PRAXY: GENdEr and Sex DetermInantS of Cardiovascular Disease: From Bench to Beyond PRemature Acute Coronary SYndrome.

Igor Karp

 

Why do some people suffer an acute coronary syndrome (ACS) early in their life? Why are men more commonly affected than women? Why do you women loose their biological advantage and present with ACS at a young age? What are the medical and psychosocial impacts of premature ACS?· Answers to these questions are needed because the clinical, psychosocial, and economic impact of ACS at young age is enormous. Aside from the fact that the ACS can be fatal and manifest in sudden death, even non-fatal ACS morbidity represents considerable loss of years of productive life. While numerous studies have tried to address these issues and described sex differences in various aspects of ACS, the interpretation of these findings has been challenging and the evidence is still conflicting especially in the young ACS patients. A major reason has been that female ACS patients tend to be older and suffer from more co-morbid illnesses; therefore, valid women-men comparisons are challenging, even with the use of multivariate analytic methods. Restriction of a study of sex differences to a younger population will render women and men more comparable in terms of co-morbidities.

The importance of premature ACS and considerable gaps in current knowledge on the sex differences led the multi-disciplinary, pan-Canadian research group making up the GENESIS (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond) team to embark on this large scale project.· The GENESIS team is a much-wanted outcome of the Interdisciplinary Capacity Enhancement (ICE) team program launched by the CIHR and other research agencies such as the Heart and Stroke Foundation. GENESIS will conduct a multi-center, interdisciplinary, epidemiologic study, the GENESIS PRAXY (PRemature Acute Coronary SYndrome), to explore sex differences and their determinants in several important aspects of premature ACS.· Such a network will be instrumental in conducting a large prospective cohort study with the objectives to identify and explain sex differences in:· 1) prognosis, medical and psychosocial outcomes after premature ACS; 2) access to and patterns of health care utilization after premature ACS and 3) clinical presentation of premature ACS. Potential determinants (behavioral, environmental, psychosocial, clinical, biological of presentation and of health care utilization and outcomes after premature ACS and their interaction with sex will be the focus of this investigation.

 

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Igor Karp

 

Many of the putative genetic associations with ACS could be false positive as a result of multiple testing and publication bias. Thus, results from previous studies on the role of genes in the etiology of ACS need to be independently replicated. Further, little is known about the potential interactions between the susceptibility genes and sex, as well as with other conventional coronary risk factors.

We will use a case-only design. We have access to frozen blood samples and detailed data collected on 1000 subjects admitted to ten Quebec hospitals with ACS (including both acute myocardial infarction and unstable angina). These patients will serve as the case series. Detailed questionnaires will be administered to the control patients, and blood samples will be collected among them. The candidate genes will be selected based on the following criteria: (i) the gene's product biological function suggests that its polymorphism(s) could play a role in susceptibility to ACS; (ii) a significant association with ACS in humans has been previously reported in the literature for certain polymorphisms(s) of the gene; (iii) the prevalence of the homozygous genotype for the minor allele is expected to be at least 5%. Genotyping will be performed at the Genome Quebec and McGill University Innovation Centre (Montreal). Logistic regression models will be fitted to test the associations between each genotype and sex among the cases only. The derived risk ratios (RR) will provide the estimates of the multiplicative interaction factor. Analogous models will be fitted to estimate the multiplicative interactions of each polymorphism with diabetes and smoking.

 

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Tracie Barnett (PI); Anita Koushik

 

Canadian Institutes for Health Research (CIHR)

 

The overarching aim is to identify characteristics of residential and school environments that most strongly influence adiposity, fitness, and related behaviours (physical activity, sedentary behaviour, dietary behaviour) in children at risk of obesity due to their parental history. Outcomes are already being assessed at baseline and 2 year follow-up as part of the QUALITY study, a population-based cohort study investigating the natural history of excess weight in children aged 8-10 years. Funding to investigate aspects of residential and neighborhood environments has recently been obtained; the purpose of the current proposal is to collect complementary data on school environments. In this study, attributes of school features and policies will be assessed, and the extent to which these influence weight status, and behaviours that influence weight status, will be examined. We will also examine how these primary relationships are affected by child's gender, attitudes, and beliefs; parental modeling and support of healthy behaviours; and neighbourhood social environment. It has become urgent to address the current pediatric obesity crisis; in partnership with community, schoolboard, and public health representatives, this study will identify health promotion targets designed to create healthy school environments that support healthy choices.

 

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Mark Goldberg (PI); Simard J., Durocher F., Labrèche F., Parent M.-É., Langholz B., Sinnett D.

 

Quebec Breast Cancer Foundation

 

Female breast cancer is a major public health concern in the industrialised world.· It is the most commonly diagnosed malignancy among Canadian women, and it accounts for about 30 percent of all new cases of cancer.· About one in nine Canadian women is expected to develop breast cancer in her lifetime and one in 25 women is expected to die from the disease.· It is the second most common cause of death from cancer, accounting in 1999 for an estimated 18% of all cancer deaths among Canadian women.

 

We and others have postulated that exposures to certain chemical and physical agents may increase the risk of developing breast cancer, including organic solvents, pesticides, polycyclic aromatic hydrocarbons (PAH), and extremely low-frequency magnetic fields (EMF) and light-at-night. Common genetic polymorphisms of low penetrance such as those that code for the cytochrome P450 Phase I oxidizing enzymes (the family of CYP genes) and Phase II detoxifying or conjugating enzymes (e.g., glutathione s-transferase (GST) and n-acetyl transferase (NAT)) are recently drawing researchers' interest. Cytochrome P450 enzymes are important factors in steroidogenesis and in detoxifying environmental chemicals such as PAHs and benzo(a)pyrene.· Research in gene-environment interactions in breast cancer is in its infancy, with only a handful of high quality studies having been completed.

The objective of the present proposal is to determine whether common polymorphisms for selected genes (e.g., CYPs, GSTs) and selected steroids circulating in the blood combined with lifestyle/demographic characteristics (e.g., alcohol, physical activity, reproductive factors, body size, hormonal replacement therapy, exposure to light-at-night and shift work) are associated with the incidence of postmenopausal breast cancer.

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Anita Koushik (PI), Jack Siemiatycki, Michal Abrahamowicz, Anne-Marie Mes-Masson, Diane Provencher, Edgard Delvin, Marie-Pierre Dubé

 

Ovarian cancer is the fifth leading cause of cancer death among Canadian women and ranks as the most lethal of the gynecological malignancies. The high case-fatality is a consequence of the advanced stage at which ovarian cancer is usually diagnosed. Unfortunately, early symptoms are vague and not easily recognized. Furthermore, effective measures to screen for early disease currently do not exist. Primary prevention thus offers the most promising approach to reducing the morbidity and mortality associated with this deadly disease. Established preventive factors for ovarian cancer include high parity, long duration of lactation, oral contraceptive use and tubal ligation. However, the ability to modify these reproductive factors is limited. There is suggestive evidence that modifiable factors in the vitamin D pathway (sun exposure, diet) and inflammation pathway (anti-inflammatory medication use, talc use for feminine hygiene) may play a role in ovarian cancer risk, though this research has been limited by small sample sizes, crude exposure measurement and lack of control for important confounders. In this study, we are assessing vitamin D and inflammation exposures, in addition to other lifestyle factors, to identify possible modifiable factors that can contribute to ovarian cancer prevention.