Extended Follow-Up and Spatial Analysis of the American Cancer Society Study Linking Particulate Air Pollution and Mortality

EPA Grant Number: R832347C140
Subproject: this is subproject number 140 , established and managed by the Center Director under grant R832347
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Health Effects Institute (2005 — 2010)
Center Director: Greenbaum, Daniel S.
Title: Extended Follow-Up and Spatial Analysis of the American Cancer Society Study Linking Particulate Air Pollution and Mortality
Investigators: Krewski, Daniel
Institution: Health Effects Institute , Desert Research Institue , Michigan State University , University of Medicine and Dentistry of New Jersey , University of Ottawa
EPA Project Officer: Chung, Serena
Project Period: April 1, 2005 through March 31, 2010
RFA: Health Effects Institute (2010) RFA Text |  Recipients Lists
Research Category: Health Effects , Air


The American Cancer Society (ACS) Cancer Prevention Study II (CPS-II), a large ongoing prospective study of mortality in adults initiated in 1982, was one of two U.S. cohort studies central to the 1997 debate on the National Ambient Air Quality Standard (NAAQS) for fine particulate air pollution in the United States. Because of the high importance of the original ACS study in formulating regulations and the controversy generated by the limitations of that study, the U.S. Environmental Protection Agency (U.S. EPA), the Congress, and industry requested that the Health Effects Institute conduct the Particle Epidemiology Reanalysis Project with the objective of independently and rigorously assessing the original data and findings. The results of the Reanalysis Project validated the quality of the original data (which included 7 years of followup), replicated the original results, and tested those results against alternative risk models and analytic approaches.

After the Reanalysis Project, Dr. Arden Pope and colleagues undertook an Updated Analysis of the ACS cohort using an additional 10 years of followup and exposure data. Recent advances in statistical modeling were incorporated into these analyses.

As described in Research Report 140, Dr. Daniel Krewski and colleagues, with HEI’s support, conducted an Extended Analysis of the same cohort. This research increases the follow-up period for the ACS cohort to 18 years (1982 to 2000) — 11 years more than the original study. The investigators have produced national estimates of the risks of death from various causes and have extended the range of analyses to include refinements of statistical methods and incorporate sophisticated control of bias and confounding.


The cohort for the current study consists of approximately 360,000 participants residing in areas of the country that have adequate monitoring information on levels of particulate matter with an aerodynamic diameter of 2.5 μm or smaller (PM2.5) for 1980 and about 500,000 participants in areas with adequate information for 2000. The causes of death obtained from death certificates during follow- up that were analyzed included all causes, cardiopulmonary disease (CPD), ischemic heart disease (IHD, reduction of blood supply to the heart, potentially leading to heart attack), lung cancer, and all remaining causes. Data for 44 personal, individual-level covariates, based on participants’ answers to a 1982 enrollment questionnaire, were also used for the analyses. Dr. Krewski’s research team also collected data for seven ecologic (neighborhood- level) covariates, each of which represents local factors known or suspected to influence mortality, such as poverty level, level of education, and unemployment (at both Zip Code and city levels).

Long-term average exposure variables were constructed for PM2.5 from monitoring data for two periods: 1979–1983 and 1999–2000. Similar variables were constructed for long-term exposure to other pollutants of interest from single-year (1980) averages, including total suspended particles, ozone (O3), nitrogen dioxide, and sulfur dioxide (SO2). Exposure was averaged for all monitors within a metropolitan statistical area (MSA) and assigned to participants according to their Zip Code area (ZCA) of residence.

Dr. Krewski’s team chose the standard Cox proportional- hazards model (and a variation to allow for random effects) to calculate hazard ratios for various cause-of-death categories associated with the levels of air pollution exposure in the cohort. They extended the random effects Cox model to accommodate two levels of information for clustering and for ecologic covariates. Three main analyses were conducted: a Nationwide Analysis, Intra-Urban Analyses in the New York City (NYC) and Los Angeles (LA) regions, and an analysis designed to investigate whether critical time windows of exposure to pollutants might have affected mortality in the cohort.

Progress and Final Reports:

  • 2005
  • 2006
  • 2007
  • 2008
  • Final

  • Main Center Abstract and Reports:

    R832347    Health Effects Institute (2005 — 2010)

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R832347C135 Mechanisms of Particulate Matter Toxicity in Neonatal and Young Adult Rat Lungs
    R832347C136 Uptake and Inflammatory Effects of Nanoparticles in a Human Vascular Endothelial Cell Line
    R832347C138 Health Effects of Real-World Exposure to Diesel Exhaust in Persons with Asthma
    R832347C140 Extended Follow-Up and Spatial Analysis of the American Cancer Society Study Linking Particulate Air Pollution and Mortality
    R832347C141 Air Pollution Effects on Ventricular Repolarization
    R832347C143 Measurement and Modeling of Exposure to Selected Air Toxics for Health Effects Studies and Verification by Biomarkers
    R832347C144 Genotoxicity of 1,3-Butadiene and Its Epoxy Intermediates
    R832347C145 Effects of Concentrated Ambient Particles and Diesel Emissions on Rat Airways
    R832347C147 Atmospheric Transformation of Diesel Emissions