Biography

Dr. Ward received an M.S. in ecology from the University of Tennessee and a Ph.D. in epidemiology from The John Hopkins School of Hygiene and Public Health. Her research focuses on environmental and occupational causes of cancer, with special emphasis on pesticides and nitrates in relation to the etiology of childhood leukemia, non-Hodgkin’s lymphoma, gastrointestinal cancers, and thyroid cancer. She is examining the etiologic role of nitrosamines and their precursors with respect to drinking water and dietary ingestion for cancers of the brain, bladder, colon, pancreas, stomach, esophagus, and thyroid. Dr. Ward is responsible for developmental work using geographic information systems for exposure assessment of environmental contaminants. For this effort, she received a DCEG Intramural Research Award in 1999 and an NIH Merit Award in 2000.

Research Interests

Nitrates, Pesticides and Cancer and Environmental Exposure Assessment

We are using innovative methods such as geographic information systems (GIS) to display and analyze environmental exposure data. Using GIS and remote sensing data, we are participating in interdisciplinary collaborations to develop new methods of exposure assessment for epidemiologic studies of cancer risk in relation to drinking water contaminants and agricultural pesticides.

Nitrates

The endogenous formation of carcinogenic N-nitroso compounds (NOC) can occur following ingestion of nitrate from drinking water. Certain foods are also sources of these agents. Nitrate can also inhibit iodide uptake by the thyroid. Only a limited number of analytic epidemiologic studies have evaluated this exposure issue with respect to diet and drinking water. We conducted case-control studies that found an increased risk of colon and kidney cancer associated with prior exposure to elevated nitrate in drinking water among those who also had lower intakes of vitamin C and higher intakes of red meat, inhibitors and precursors in the endogenous formation of NOC. Increasing intake of dietary nitrite, a major source of which is processed meats, was associated with increased risk of colorectal adenomas, colon, rectum, and pancreas cancers. Additional analytic studies are underway to evaluate further the importance of drinking water and dietary sources of nitrate and nitrite in the etiology of gastrointestinal tumors and thyroid cancer.

To further evaluate the possible role of drinking water nitrate exposure in the development of cancer, we are conducting an ecologic study of cancer incidence in the Platte River Valley of Nebraska and Colorado, an area with some of the highest drinking water nitrate levels in the country. Population exposure via both community water supplies and private wells is being characterized at the block group level. Annual monitoring data is being used to characterize the population exposed to nitrate through community water systems. Through an interdisciplinary collaboration with colleagues in hydrology, engineering and remote sensing, information about land use, fertilizer application rates, the location of livestock feeding operations, soil type, and other factors are being incorporated into a GIS to estimate levels of nitrate in drinking water for the population using private wells.

Pesticides

A feasibility study using remote sensing data and a GIS to estimate indirect exposure to pesticides demonstrated that using available data, accurate historical crop maps could be produced and that these could be linked to pesticide use data to estimate probabilities of indirect exposure to agricultural pesticides. A total of 24% of the study population in an agricultural area of Nebraska were determined to live within 500 meters of crop fields likely to have been treated with pesticides. This was the first study to estimate the prevalence of potential indirect exposure to agricultural pesticides in the general population. A validation study in Iowa found that 58% of residences had crops within 500 m of their home, an intermediate distance for primary drift from aerial and ground applications. Six herbicides used almost exclusively in agriculture were detected in 28% of homes. Increasing acreage of corn and soybean fields within 750 m of homes was associated with significantly elevated odds of detecting agricultural herbicides compared with homes with no crops within 750 m even after accounting for the presence of an occupational exposed worker.

With collaborators in California, we are evaluating agricultural pesticide use near residences as a risk factor for childhood leukemia in an ongoing case-control study. Carpet dust samples have been analyzed for pesticides and other chemicals, and information about the current and historical location of crops near residences was determined. Analyses of persistent organochlorine pesticides and polychlorinated biphenyls in carpet dust samples revealed an increased risk of acute lymphocytic leukemia among children living in homes with higher levels of polychlorinated biphenyls; we observed no significant associations with other persistent organochlorine chemicals such as DDT, DDE, or chlordane. Ongoing analyses are also evaluating concentrations of polycyclic aromatic hydrocarbons and pesticides used in and around the home in relation to risk of leukemia.

Chemicals

Using a GIS, residential proximity to specific industries, hazardous waste sites, and specific chemical releases as reported by the Environmental Protection Agency's Toxic Release Inventory are being evaluated in a multi-center study of non-Hodgkin's lymphoma. Plans are underway to do a similar type of an analysis in a recently completed bladder cancer study in New England.

Keywords

agricultural exposures, bladder cancer, brain cancer, childhood leukemia, drinking water contaminants, environmental carcinogens, exposure assessment, geographic information systems, nitrate, N-nitroso compounds, non-Hodgkin's lymphoma, stomach cancer

Selected Publications

• Ward MH, Colt JS, Metayer C, Gunier RB, Lubin J, Nishioka MG, Reynolds P, Buffler PA. Residential exposure to polychlorinated biphenyls and organochlorine pesticides and risk of childhood leukemia. Environ Health Perspect (in press).
• Shen M, Cozen W, Huang L, Colt J, De Roos AJ, Severson RK, Cerhan JR Bernstein L, Morton LM, Pickle L, Ward MH. Census data and geographic differences between respondents and non-respondents in a case-control study of non-Hodgkin lymphoma. Am J Epidemiol 167:350-361; 2008.
• Ward MH, Cross AJ, Divan H, Nowell-Kadlubar S, Kadlubar F, Sinha R. Processed meat intake, CYP2A6 activity, and risk of colorectal adenomas. Carcinogenesis 28:1210-16; 2007.
• Ward MH, Rusiecki J, Lynch C, Cantor KP. Nitrate in public water supplies and risk of renal cell carcinoma. Cancer Causes Control 18:1141-51;2007.
• Ward MH, Lubin J, Giglierano J, Wolter C, Colt JS, Bekiroglu N, Camann D, Hartge P, Nuckols JR,. Proximity to crops and residential exposure to agricultural herbicides in Iowa. Environ Health Perspect 2006;114:893-7.

Collaborators

DCEG Collaborators

• Michael Alavanja, Dr.P.H.; Dalsu Baris, M.D., Ph.D.; Laura Beane-Freeman; Kenneth P. Cantor, Ph.D.; Joanne Colt, M.P.H.; Barry Graubard, Ph.D., Patricia Hartge, Sc.D.; Sonya Heltshe, Ph.D., Jay Lubin, Ph.D.; Debra Silverman, Sc.D.

Other Scientific Collaborators

• Erin Bell, Ph.D., State University of New York, Albany, NY
• Patricia Buffler, Ph.D., University of California at Berkeley, Berkeley, CA
• James Cerhan, M.D., Ph.D., Mayo Clinic, Rochester, MN
• Anneclaire De Roos, Ph.D., Fred Hutchison Cancer Research Center, Seattle, WA
• James Giglierano, M.S., Iowa Department of Natural Resources, Iowa City, IA
• Robert Gunier, M.S., Northern California Cancer Center, Berkeley, CA
• Lizbeth Lopez Carrillo, Ph.D., National Institute for Public Health, Mexico City, Mexico
• Charles Lynch, M.D., Ph.D., University of Iowa, Iowa City, IA
• Susan Maxwell, Ph.D., U.S. Geologic Survey, Sioux Falls, SD
• Jaymie Meliker, Ph.D., State University of New York, Stonybrook, NY
• Catherine Metayer, Ph.D., University of California, Berkeley, CA
• John Nuckols, Ph.D.; John Reif, D.V.M., Colorado State University, Ft. Collins, CO
• Peggy Reynolds, Ph.D., California Department of Health, Oakland, CA
• Rudy Rull, Ph.D., Northern California Cancer Center, Berkeley, CA
• Peter Weyer, Ph.D., University of Iowa, Iowa City, IA