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Identifying Environmental Carcinogens Through Epidemiology

By Jeffrey Stumpf
July 2010

Paolo  Boffetta, M.D.
Boffetta, above, has held several academic posts and is currently an adjunct professor in the Department of Epidemiology at the Harvard University School of Public Health. Prior to joining the Tisch Cancer Institute, he served as the head of the Gene-Environment Epidemiology Group at the International Agency for Research on Cancer, a unit of the World Health Organization. (Photo courtesy of Paolo Boffetta)

During his visit to NIEHS June 17, guest lecturer Paolo Boffetta, M.D., deputy director of the Tisch Cancer Institute at the Mount Sinai School of Medicine, explored the topic of "Environmental Cancer Epidemiology: Challenges and Perspectives." Hosted by NIEHS/NTP Director Linda Birnbaum, Ph.D., Boffetta's talk focused on the identification of environmental risk factors that lead to cancer, a challenge that is central to the mission of NIEHS.

As Boffetta (http://www.mssm.edu/profiles/paolo-null-boffetta) Exit NIEHS explained, a growing and aging world population with increasing exposures to environmental risk factors is projected to experience more than twice the number of cancer deaths in the next thirty years. Known risk factors include tobacco, alcohol, chronic infections, poor nutrition, hormonal changes, ionizing and solar radiation, and occupational and environmental factors such as radon decay, tobacco smoke, smoke from burning coal, asbestos, and arsenic in water.

Boffetta referred to a 2000 study in France showing that known carcinogenic risk factors, although important, explain only one-third to one-half of the incidences of cancer. According to Boffetta, carefully designed epidemiological studies can be useful in filling this knowledge gap by identifying novel environmental carcinogens that could explain some of the remaining cancer incidences.

Challenges of cancer epidemiology

Boffetta outlined several disadvantages of epidemiology studies of cancer. He said data is pooled from several studies to obtain large enough data sets needed to identify small effects. Unfortunately, such meta-studies are subject to several biases, including information bias. Also, study design and data collection may vary among different studies.

To illustrate the difficulties of cancer epidemiology, Boffetta pointed to studies of three suspected carcinogens - water-chlorinated by-products, pesticides, and outdoor air pollution. The pooling of data from six independent studies suggests a small correlation between water-chlorinated by-products and bladder cancer. Although early studies in pesticides were promising, the correlation between dichlorodiphenyldichloroethylene (DDE), a breakdown product of the banned pesticide dichlorodiphenyltrichloroethane (DDT) (http://www.atsdr.cdc.gov/tfacts35.html#bookmark02) Exit NIEHS, and breast cancer decreased in more recent studies, possibly due to more limited exposure. Although several researchers have proposed that fine particle outdoor air pollution may pose a potential lung cancer risk, Boffetta said that the available data do not support a definite conclusion.

Duration studies of lung cancer risk due to second-hand smoke have explored the association between increased lung cancer risk and number of years of exposure, but Boffetta said he found only "very weak evidence" in support of this hypothesis. One possible reason, he speculated, could be that people in the study were misclassified as smokers or nonsmokers. Also, the duration of exposure was inaccurate in some cases because the people in the study may not have quit smoking when they reported.

Solution lies in larger studies

In response to the challenges of environmental cancer epidemiology, Boffetta outlined the feasibility study for his newest project. The study will be conducted using a cohort of an estimated 300,000 middle-aged people in Daqing, China, a city whose workforce is primarily involved in oil production.

The goal of the study is to make periodic exposure assessments through biological samples while tracking lifestyle habits and medical conditions. High-risk individuals will be selected for early diagnosis and intervention. Boffetta said he is hopeful that the duration of the study will help in identifying potential carcinogens over an extended period of time. "We plan to be collecting data in three years," he explained, "but the study will hopefully go on for years to come."

Boffetta acknowledged that a large-scale study also has its potential pitfalls. The power of such a study depends to a great extent on the frequency of measuring environmental exposures. If performed infrequently, researchers will not be able to detect acute exposures. As Boffetta observed in response to a question from the audience, epidemiology studies will not determine risk factors in all cancers. Still, he believes that large-scale studies will provide greater support for the characterization of environmental exposures as carcinogens and better identify novel cancer risks.

(Jeffrey Stumpf, Ph.D., is a postdoctoral fellow in the NIEHS Laboratory of Molecular Genetics Mitochondrial DNA Replication Group.)

Audience Response

Boffetta's talk attracted an audience from throughout the Institute, including NIEHS Senior Advisor Chris Portier, Ph.D., who is part of the Institute's global health initiative. Portier was the NIEHS lead on a series of studies published in November 2009 in the medical journal The Lancet on the potential impact of climate change on household energy, transportation, electricity generation and agricultural food production. (see story (http://www.niehs.nih.gov/news/newsletter/2009/december/spotlight-climatechange.cfm))

Asked about his impression of the seminar, Portier said he agrees with Boffetta that believe epidemiological studies can contribute significantly to identifying and quantifying risks from exposure to toxic chemicals. However, these studies still pose challenges. "The difficulty," Portier observed, "is in understanding how these data, in concert with the toxicological evidence, provide evidence of serious human harm."



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