Biography

Dr. Wacholder received a Ph.D. in biomathematics from the University of Washington in 1982. Before joining NCI in 1986, he was an Assistant Professor of Epidemiology and Biostatistics at McGill University. Dr. Wacholder was elected a Fellow of the American Statistical Association in 1996. He received the NIH Merit Award in 1992, the NIH Quality of Work Life Award in 1997 for his accomplishments as the Chair of the DCEG Committee of Scientists, and the Roche Epidemiology Prize in 1997. He was awarded the NIH Director's Award in 1998 for fundamental contributions to statistical methods and outstanding collaboration within DCEG, and he received the DCEG Outstanding Mentor Award in 2000.

Research Interests

Our research agenda is driven by study design and interpretation issues facing scientists in DCEG and elsewhere who are trying to understand the causes of cancer and means for its prevention. In addition, much of our independent and collaborative work involves molecular epidemiology, which has become a major research thrust within DCEG. In both substantive and methodological work, research questions being addressed include:

• What is the best study design to apply to a particular class of scientific issues?
• How can elapsed time, cost, and number of subjects in a study be reduced?
• How serious are biases affecting epidemiologic studies?
• What should we try to estimate from studies?

Design of Epidemiologic Studies

Case-control studies. Based on a long-standing interest in the principles and practice of control selection for case-control studies, we are addressing new challenges posed by molecular epidemiology. With DCEG colleagues, we recently estimated the bias from population stratification in evaluating the effect on cancer of a common polymorphism from cohort and case-control studies with unrelated controls. We found that the bias is likely to be small in ethnically mixed populations of non-Hispanic Europeans in the United States. Another research interest involves two-phase designs in which only a fraction of individuals in a study are selected for an expensive, onerous, or time-consuming aspect of exposure assessment. Properly planned and implemented, these designs are very efficient and yield unbiased estimates of the target effects. Other interests include assessing the impact of selection bias, measuring and reporting error and confounding in epidemiologic studies, studying gene-environment interactions, and studying pathologic changes.

Cohort studies. Cohort studies allow the evaluation of many outcomes, thereby compensating for their initial high costs. Exposure data collected prospectively avoids problems in retrospective studies from differential reporting and disease influences on biochemical measurements. The cost associated with cohort studies can be reduced by efficient sampling designs, such as nested case-control and case-cohort studies, and the use of special sampling schemes. We continue to work on the theoretical and practical aspects of these approaches.

Kin-cohort design. Together with colleagues in DCEG and the National Human Genome Research Institute, we developed the kin-cohort design to estimate penetrance (risk of developing disease) of a rare mutation from a study of volunteers. This design is useful when a quick and relatively cheap estimate of penetrance is desired for individuals in families with fewer affected individuals than those normally used for linkage studies. A case series can be used instead of volunteers. Extensions of this approach allow estimating survival after diagnosis in carriers and non-carriers.

Collaboration in Epidemiologic Studies

Considerable time is spent in collaborating on a variety of DCEG studies, including decisions about whether a study should be initiated, its basic design, selection of study participants, and assessment of exposure and disease. Other important collaborative matters involve quality control and other fieldwork issues, the analytic plan and specific analyses, interpretation of results, and preparation of publications.

We are currently involved in collaborative studies of occupational (benzene and diesel) and viral (human papillomavirus) exposures, rare mutations, and metabolizing polymorphisms. Other collaborative work includes studies of leukemia and cancers of the cervix, lung, ovary, and breast. These studies provide a practical perspective to methodologic research, since they face some of the issues of case and control selection, efficient design, interpretation of joint effects of genetic and environmental factors, and exposure measurement error.

Keywords

study design, case-control studies, epidemiologic methods, statistical methods, genetic epidemiology, molecular epidemiology, gene-environment interaction

Selected Publications

• Wacholder S, et al. "The kin-cohort study for estimating penetrance." Am J Epidemiol 1998; 148:623-630.
• Hatch EE, et al. "Do confounding or selection factors of residential wiring codes and magnetic fields distort findings of electromagnetic fields studies?" Epidemiology 2000; 11:189-98.
• Wacholder S, et al. "Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias." J Natl Cancer Inst 2000; 92:1151-1158.
• Modan B, et al. "Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation." New Engl J Med 2001; 345:235-240.

Collaborators

DCEG Collaborators

• Neil Caporaso, M.D.; Mustafa Dosemeci, Ph.D.; Patricia Hartge, Sc.D.; Richard Hayes, D.D.S., Ph.D.; Alan Hildesheim, Ph.D.; Martha Linet, M.D.; Nathaniel Rothman, M.D.; Arthur Schatzkin, M.D., Dr.P.H.; Mark Schiffman, M.D.; Robert Tarone, Ph.D.; Margaret Tucker, M.D.

Other NCI Collaborators

• Michelle Forman, Ph.D.; Douglas Lowy, Ph.D.; John Schiller, Ph.D.; Jeffery Struewing, M.D.

Other NIH Collaborators

• Lawrence C. Brody, Ph.D., National Human Genome Research Institute
• Tamara Harris, M.D., Ph.D., National Institute on Aging
• Clarice R. Weinberg, Ph.D., National Institute of Environmental Health Sciences

Other Scientific Collaborators

• Baruch Modan, M.D., Chaim Sheba Hospital, Tel Hashomer, Israel
• Leslie L. Robison, Ph.D., Julie Ross, Ph.D., University of Minnesota, Minneapolis, MN
• S.N. Yin, Chinese Academy of Preventive Medicine, Beijing, China