Source: NIEHS

Environmental health seems to have little to do with Los Angeles, a metropolitan area popularly synonymous with smog. Despite much progress, Southern California continues to suffer the worst air pollution in the United States, and the nation's most ethnically diverse region is also among the most heavily industrialized. However, three leading universities in the Los Angeles area have joined forces to study the effects of air pollution and other environmental factors on human health. Faculty from the University of Southern California (USC), the University of California at Los Angeles (UCLA), and the California Institute of Technology (Caltech) make up the Southern California Environmental Health Sciences Center (SCEHSC) personnel. The center comprises five interdisciplinary research cores, four service cores, and a community outreach and education core. Two overarching themes are apparent in the center's research--the epidemiology of environmental effects on human health and gene-environment interactions.

Among inner-city children, especially minority children, asthma is a prevalent problem in southern California. This situation inspired Peters and his colleagues to undertake the Children's Health Study, a 10-year prospective study involving 4,000 children in 12 different communities. The study, now in its sixth year, seeks to determine whether air pollution plays a role in asthma and other respiratory disorders. The study also addresses questions about the potential effects of pollution on lung function. "Since we are looking at growing children, one could presume that the growing lung might be more sensitive to effects of pollution," says Peters.

Another aspect of respiratory effects research is identifying how bioaerosols found in the home, such as dust mites, pollen, and spores, may compound problems associated with pollution. "One is struck by the fact that people worry a lot about air pollution but tend to overlook a large potential problem, namely, bioaerosols," says Edward Avol, a center member and an associate professor of occupational and environmental health at USC. To foster collaborative research on the issue, the SCEHSC held a workshop on bioaerosols in April 1997 that allowed center scientists to explore the topic with key investigators from other universities.

Shared environmental problems have also forged strong links between SCEHSC researchers and their counterparts in Mexico and China. In Mexico City, researchers are collaborating with colleagues at the National Institute of Respiratory Diseases and the National Institute of Public Health on gathering data comparable to that of the Children's Health Study. In Wuhan, China, the center is poised to begin a collaborative study with the Public Health and Anti-epidemic Station that will assess children's risks of developing asthma and other respiratory disorders as a result of air pollution. This research may also help genetic epidemiologists explore the variance in asthma rates between Los Angeles and Wuhan. "Asthma rates, despite the fact that [Wuhan is] a polluted city, seem to be much lower [there] than they are in the United States, and nobody knows quite why. Whether it's the way we diagnose asthma or whether it's genetic is unknown," says Peters.

Owing to the continuing eruption of Hawaii's Kilauea volcano, the largest active crater in the world, the Island of Hawaii suffers a corollary to Los Angeles's smog: a combination of volcanic ash and gases called "vog." Respiratory core members have also been working with researchers in Hawaii to determine the possible relationship between vog and asthma. "There are a lot of anecdotal reports from the community about increased asthma, increased respiratory infections, and increased health problems," says Avol, "but there's not a clear association between the volcanic emissions being present in the area and these respiratory problems." To assess the risk of such problems, center staff are providing training support for air sampling studies by the Hawaii Department of Health, to be followed by an assessment of acute and chronic respiratory health effects.

The SCEHSC adult cancer core focuses on the relationship between cancer and environmental factors, as well as on the gene-environment interactions that may modulate individual responses. "We define environment broadly in our program," says Ronald Ross, a professor of preventive medicine at the USC School of Medicine and director of the adult cancer research core. "To us, environment is everything that's not genetic. We define environment to include dietary factors, exogenous drug exposures, and estrogenic exposures such as oral contraceptives and exogenous hormones, along with the more traditional environmental contaminants."

Another gray day in L.A. Although improving, smog in southern California contributes to a variety of respiratory problems including asthma.

This approach is reflected in projects such as the research being performed by Giske Ursin, an assistant professor of preventive medicine at the USC School of Medicine. In the 1 September 1997 issue of Cancer Research, Ursin and her colleagues published preliminary results of a study suggesting that the risk of breast cancer associated with long-term (more than 4 years) oral contraceptive use may be up to six times higher in women with BRCA gene mutations than in other women.

In addition to hormonal links to cancer, the adult cancer core is also investigating the role of metabolism in cancer. For example, Ross explains that approximately 50-60% of all bladder cancer cases in the United States are linked to cigarette smoking. Tobacco smoke contains arylamines, carcinogenic compounds that are metabolized by enzymes such as N-acetyltransferase and glutathione S-transferase. Ross and his colleagues are investigating whether variations in the genes for these enzymes may explain disparate bladder cancer rates among different racial groups. "We are interested not only in understanding how individual variation of metabolism of smoking-related carcinogens might alter risk of bladder cancer, but [also in] further understanding how population differences in metabolism might explain these discrepancies," states Ross. "Exploring the genes that encode these kinds of enzymes is going to give us serious insights as to why we see extreme differences [in cancer rates] among different populations."

Gene-environment interactions are also investigated in the childhood cancer research core. Jonathan Buckley, a professor of preventive medicine at USC and core director, explains that one of the center's concerns is secondary cancers following treatment of a primary malignancy. There are indications that some children may have a genetic predisposition to develop cancer as a result of chemotherapy or radiation therapy. Other research in the childhood cancer core focuses on environmental contaminants such as polycyclic aromatic hydrocarbons and pesticide residues in household dusts. A recent study of children with brain tumors (See EHP 105[11]:1214-1220) conducted by Susan Preston-Martin, a professor of preventive medicine at the USC School of Medicine, and colleagues found an elevated risk associated with prenatal exposure to flea and tick pesticides, although pinpointing specific chemicals using data from the study was not possible.

Typically, exposure assessment and statistics play supporting roles in epidemiologic research; however, at the SCEHSC, these fields boast separate research cores. "I think this center is unique insofar as exposure assessment constitutes its own research core," says John Froines, chair of environmental health sciences at the UCLA School of Public Health and director of the exposure assessment core. "An important goal is improving exposure assessment methodology, as well as developing better collaborative exchanges with epidemiologists on their investigations," he explains. At the center's outset, Froines and his colleagues were determined to address the need to improve exposure assessment, and founded the Southern California Exposure Assessment Group. This group comprises researchers from several institutions in southern California whose primary interest is exposure assessment. The group meets on an ongoing basis with epidemiologists to develop new research, Froines says. Backed by a grant from the National Institute for Occupational Safety and Health, Froines and his colleagues are currently tackling the issue of multiple chemical exposures. The potential health effects of the many chemicals and allergens present in paved road dust generated by traffic in Los Angeles are being studied by another exposure assessment core member, Glen Cass, a professor of environmental engineering at Caltech.

The SCEHSC statistics core confronts design and analysis issues that arise in epidemiologic research. "I see the field of genetic epidemiology as divided into two subdisciplines," says Duncan Thomas, a professor of biostatistics and genetic epidemiology at USC and director of the statistics core. "Some researchers are concerned with trying to discover genes and others are involved in trying to characterize them from a population perspective." One of the problems in characterization, Thomas explains, is that cohort studies require large numbers of study participants. A case-control study requires fewer people, but because it is subject to various potential biases, may not carry enough statistical weight to allow application to the population at large. A design that Thomas helped develop in the 1970s creates a happy medium. Nested case-control studies use cohorts to define the initial study population, identify cases within the cohort, and draw controls from the same cohort. The center is using this approach with various modifications to study issues such as estimating the effects of genes and environmental exposures within populations.

Playing with fire. The SCEHSC is working with Communities for a Better Environment on environmental justice issues such as the location of manufacturing facilities near playgrounds and schools.
Photo Credit: Communities for a Better Environment, used with permission

Although the SCEHSC has existed for only two years, it has already established strong links to the community. "First, we are trying to understand the environmental health concerns of the community, as they relate to research we might conduct," explains Andrea Hricko, program director of the center. "Then we are helping community groups evaluate the science so that they are on solid footing when they publicly raise community health concerns." To meet this goal, the center offers technical assistance to grassroots community empowerment groups such as Communities for a Better Environment and Mothers of East Los Angeles. Assistance may be as simple as explaining how to use PubMed, the National Library of Medicine's scientific and medical citation search engine, or as technical as assessing soil and air samples for chromium contamination.

Working with schoolchildren is an integral part of the center's outreach efforts, says Hricko. Several scientists in the center have helped to develop curricula for middle school science teachers or have hosted school field trips to center laboratories. "We think that having children become enthusiastic and knowledgeable about how scientists investigate environmental health issues is a critical part of what our center is doing," explains Hricko.

Peters adds that many of the SCEHSC's outreach efforts have evolved from community concerns about the possible links between environmental hazards and cancer, asthma, and other respiratory problems--all areas of expertise in the center. The distinct advantage of the center," notes Peters, "is that different disciplines are brought together to work on complex issues that one investigator could never address alone."