1. An Introductory Lecture to Environmental Epidemiology Part 1. Introductory Examples. Mark S. Goldberg INRS-Institut Armand-Frappier, University of Quebec, and McGill University July 2000

2. The author Dr. Mark Goldberg obtained his MSc in 1985 and his PhD in 1991 from McGill, both degrees in epidemiology and biostatistics. Dr. Goldberg is an associate professor at the INRS-Institut Armand-Frappier, University of Québec, and is adjunct professor at McGill University. He currently holds a health research scientist award from Health Canada.

3. His main interests are in occupational and environmental epidemiology, including cancer in textile manufacturing workers, health effects of exposures from municipal solid waste landfill sites, the relationship between ionizing radiation and cancer and reproductive outcomes, and the connection between tobacco smoking and back pain.

4. Currently, he is conducting research into the short- and long-term effects of air pollution, environmental case-control studies of breast cancer, and a study of waiting times for treatment of breast cancer in Quebec. Dr. Goldberg has published about 40 papers in scientific peer-review journals, is the recipient of research funds from a number of organizations, and sits on a number of scientific review panels.

5. Objectives This is the first in a five-part series of an introductory lecture on environmental epidemiology. The goal of the lecture is to provide the student with a basic understanding of the elements of environmental epidemiology. Throughout the lecture, examples from the literature are used to illustrate the basic methods. It is assumed that the student is familiar with basic epidemiology and with regression techniques.

6. Environmental Epidemiology The study of the determinants of the distributions of disease that are exogenous to and nonessential for the normal functioning of human beings l Adapted from Hertz-Piccioto (in Rothman and Greenland, 1998)

7. Types of Environmental Exposures Point sources Pollution from factories, municipal solid waste sites Line sources EMF exposures from high tension power lines Pollutants from internal combustion engines around motorways

8. Area sources Long-range transport of combustion products from traffic Volatile organic compounds contaminating underground water reservoirs

9. Example: Cancer Rates Near a Solid Waste Landfill Site Ecological Analysis (Goldberg et al., Arch Environ Health 1995;50:417-24) : Landfill site opened in 1968 100,000 persons lived within 2 km of the site In 1993, it contained about 36x10 6 Tons of domestic, commercial, & industrial waste

10. Rates for men and women living in zones around site 1981-1988 Zones defined by 3-character postal codes (fairly large areas) Putative “upwind” and “downwind” zones Putative “unexposed” zone far from the site

11. The “High” zone surrounds the landfill site to about 1 mile. The “High A” zone is downwind and the “High B” zone is upwind; because of the crude geographic identifiers, there is a region directly surrounding the site that is in both sub-zones. The “Medium” zone is further away from the site and exposure was likely to be very limited.

12. Map of the site showing the different exposure zones

13. Poisson regression adjusted for age and year, by sex Reference zones selected from the “unexposed” areas to ensure similarities for: average household income proportion of immigrants proportion first language was French unemployment and poverty rates

14. Matching was not entirely successful, as some key factors were dissimilar (e.g., percentage of persons with an Italian family background)

15. Analytic study (Goldberg et al., Arch Environ Health 1999;54:291-6) Multi-site cancer case-control study of occupation, men, 1979-85 Distance from site and by geographic zones (at time of interview)

16. Logistic regression for each site of cancer, adjusted for occupational and nonoccupational risk factors Age, family income, cigarette smoking, alcohol consumption, ethnicity, place of birth, body mass index, consumption of vitamins, occupational “salubrity”

17. Relative Risks for Cancer

18. Relative Risks for Liver Cancer from the Case-control Analysis

19. Conclusions 1) Slightly different results obtain using different methodologies. Populations were somewhat different, although there was an overlap. 2) The results are inconclusive, except perhaps for liver cancer. Vinyl chloride monomer is one of the constituents of the biogas, and this is an accepted liver carcinogen.

20. 3) Further studies are needed at other landfill sites. Results from such studies may be difficult to generalize if the constituents of the biogas differs and if exposure patterns in populations vary considerably.

21. Another Ecological Example The following example is a complex longitudinal cohort study undertaken for the purposes of determining whether air pollution affects pulmonary function. The analysis presented here is for mortality and the comparison is between six cities in the US. As in the preceding case-control study, this study can be viewed as an ecological study standardized for personal risk factors.

22. Example: Harvard Six-cities Study (Dockery et al, NEJM 1993;329:1753-9) Prospective cohort study of about 8,000 subjects selected randomly from 6 US cities with different levels of air pollution Subjects followed every two years and lung function and questionnaires administered periodically Ambient air exposures assessed from special fixed-site monitoring stations (particles, sulfates, gaseous pollutants)

23. Mortality analyses, comparing mean annual levels in each city for years near start of followup Assumed that subjects did not move during followup and that the rank ordering of cities for levels of air pollution was invariant of followup time Stratified Cox proportional hazards models to estimate cause-specific relative risks

24. Mortality rates by level of pollution by city and by pollutant

25. Estimates of Relative Rates of Mortality, Comparing Most Exposed to Least Exposed City This analysis is a Cox regression analysis comparing the most polluted city (Steubenville) to the least polluted city (Portage). The range of exposures for fine particles is about 18.6 µg/m 3. A wide range of key risks factors were included in the statistical model.

27. References Environmental Epidemiology Hertz-Piccioto, I. “Environmental Epidemiology”, in Rothman and Greenland: Modern Epidemiology, Second edition, Lippincott-Raven Publishers, 1998, Philadelphia, Chapter 28, pages 555-583.