Biography

Dr. Silverman received a Sc.D. in epidemiology from the Harvard School of Public Health and a Sc.M. in biostatistics from The Johns Hopkins Bloomberg School of Hygiene and Public Health. She joined the NCI as a biostatistician in 1972, and has served as a cancer epidemiologist since 1983. She was appointed an adjunct faculty member in the Department of Family Medicine at Georgetown University School of Medicine in 1984. Dr. Silverman received the PHS Special Recognition Award for research on environmental determinants of bladder and other cancers, the American Occupational Medical Association Merit in Authorship Award for her paper on a job/exposure linkage system, the NIH Merit Award, and the PHS Lucy Minnigerode Award for research on diesel exhaust markers. She was a finalist for the CDC Alice Hamilton Science Award for Occupational Safety and Health for her research on diesel exhaust exposure and lung cancer. Dr. Silverman is an elected member of the American Epidemiological Society and a Fellow of the American College of Epidemiology.

Research Interests

Environmental and Host Determinants of Cancer

Our research involves the design and conduct of epidemiologic investigations to evaluate environmental and host determinants of cancer. We closely monitor new findings from clinical observations, experimental studies, and descriptive and analytic epidemiology for leads as to causes of cancer. My research focuses particularly on the etiology of cancers of the bladder and pancreas and on the carcinogenic effects of diesel exhaust.

Pancreatic Cancer

We are conducting epidemiologic studies to identify risk factors that play a role in the etiology of pancreatic cancer and, in particular, contribute to the high rates experienced by African Americans. Because of the poor prognosis associated with this cancer, many previous case control studies were based largely on interviews with proxy respondents, who often lacked detailed information on relevant environmental exposures. We addressed this shortcoming in a population based, case control study in the United States in which more than 500 cases and 2,100 controls were interviewed directly. Our findings confirmed the causal link between cigarette smoking and risk of pancreatic cancer. Although consumption of alcohol at levels typically consumed within the general population did not appear to be associated with risk, heavy drinking may increase risk. Both African-American men and women had significantly higher risks associated with heavy alcohol drinking than whites. Obesity also increased risk of pancreatic cancer, and appeared to contribute to the higher rates observed among African-Americans, particularly among women. A role for energy balance in pancreatic carcinogenesis was suggested by a significant interaction between body mass index and total caloric intake, which was consistent by race and gender. Diabetes mellitus also increased pancreatic cancer risk, as well as being a possible complication of the tumor. These findings support the key role played by hyperinsulinemia in pancreatic carcinogenesis, particularly among non diabetics with elevated body mass index. An increased risk was also observed among first degree relatives of affected individuals. A link to hereditary non polyposis colon cancer was suggested by elevated risks associated with a family history of cancers of the colon, endometrial, ovary, and breast. We are currently assembling pathologic samples from the histologically confirmed cases of pancreatic cancer, which we will examine for genetic and tumor specific markers. The markers will also be evaluated for associations with data already collected on risk factors.

Bladder Cancer

Bladder cancer is recognized as an occupationally-related tumor. During the past three decades, scores of bladder cancer studies have suggested more than 40 high risk occupations, yet the specific exposures responsible for most of the excess risks remain largely unknown. Suspect occupational bladder carcinogens include diesel exhaust, oil mist, solvents, polycyclic aromatic hydrocarbons, aryl hydrocarbons, asbestos, and aromatic amines and their derivatives, such as methylene bis orthochloroaniline, dichlorobenzidine, orthotoluidine, magenta, auramine, and azo dyes. To clarify the role of these occupational agents, we are using newly developed techniques of exposure assessment in a case control study of bladder cancer in heavily industrialized areas of Spain. The study will also evaluate several non occupational exposures, including cigarette smoking (black vs. blond tobacco), phenacetin containing analgesics, dietary factors, urinary tract infections, urination habits, urinary pH, fluid intake, and air and water pollution. Biologic specimens are being collected, which will be used to examine genetic susceptibility (e.g., CYP1A1, CYP1A2, NAT1, NAT2, GSTM1, DNA repair capacity, and mutagen sensitivity) and tumor markers (e.g., H ras and p53) on risk of bladder cancer, and on their interaction with epidemiologic risk factors.

Carcinogenicity of Diesel Exhaust

Diesel exhaust is a general airborne contaminant that is classified by the International Agency for Research on Cancer as a probable human carcinogen. Exposure is ubiquitous in cities and among commuters who regularly use highways. Occupational exposures are common among transportation workers and operators of diesel powered equipment. Some workers, such as miners who use diesel powered equipment underground, may experience high levels of exposure. Although at least 30 studies have examined lung cancer risk and diesel exhaust, few used quantitative exposure measurements of diesel exhaust directly in their analyses. As a consequence, the risk of lung cancer associated with diesel exhaust is still not well defined. In collaboration with the National Institute for Occupational Safety and Health, we are conducting a retrospective cohort mortality study and nested case control study of lung cancer among non metal miners to estimate lung cancer risk in relation to quantitative measures of exposure to diesel exhaust. Excess mortality from other causes of death will also be evaluated. An intrinsic part of this research effort is an extensive effort to characterize current and historical exposures to diesel exhaust and to develop estimates of personal exposures.

Keywords

alcohol drinking, bladder cancer, cigarette smoking, diesel, dietary factors, energy intake, lung cancer, obesity, occupational epidemiology, pancreatic cancer

Selected Publications

• Silverman DT, et al. "Dietary and nutritional factors and pancreatic cancer: a case control study based on direct interviews." J Natl Cancer Inst 1998; 90:1710-1719.
• Silverman DT, et al. "Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer." Br J Cancer 1999; 80:1830-1837.
• Boffetta P and Silverman, DT. "A meta analysis of bladder cancer and diesel exhaust exposure." Epidemiology 2001; 12:125-130.
• Silverman DT. "Risk factors for pancreatic cancer: A case control study based on direct interviews." Teratog Carcinog Mutagen 2001; 21:7-25.

Collaborators

DCEG Collaborators

• Dalsu Baris, M.D., Ph.D.; Linda Brown, Dr.P.H.; Kenneth Cantor, Ph.D.; Susan Devesa, Ph.D.; Mustafa Dosemeci, Ph.D.; Montserrat Garcia Closas, M.D., Dr.P.H.; Gloria Gridley, M.S.; Robert Hoover, M.D., Sc.D.; Richard Hayes, D.D.S., Ph.D.; Bu Tian Ji, M.D., Dr.P.H.; Nathaniel Rothman, M.D.; Mark Schiffman, M.D.; Patricia Stewart, Ph.D.; Sholom Wacholder, Ph.D.; Shelia Zahm, Sc.D.

Other NIH Collaborators

• Linda Pottern, Ph.D., National Heart, Lung and Blood Institute
• Christine Swanson, Ph.D., Office of Dietary Supplements, Office of the Director, NIH

Other Scientific Collaborators

• Michael Attfield, Ph.D., National Institute for Occupational Safety and Health, Morgantown, WV
• Paolo Boffetta, M.D., International Agency for Research on Cancer, Lyon, France
• Raymond Greenberg, M.D., Medical University of South Carolina, Charleston, SC
• Manolis Kogevinas, M.D.; Nuria Malats, M.D.; Paco Real, M.D., Institut Municipal d'Investigacio Medica, Barcelona, Spain
• Betsey Kohler, M.S., New Jersey State Department of Health, Trenton, NJ
• Jonathan Liff, M.D., Emory University, Atlanta, GA
• Keith Lillemoe, M.D., The Johns Hopkins University School of Medicine, Baltimore, MD
• Ann Schwartz, Ph.D., University of Pittsburgh, Pittsburgh, PA
• Marie Swanson, Ph.D., Michigan State University, East Lansing, MI