Biography

Dr. Wacholder received a Ph.D. in biomathematics from the University of Washington in 1982. Dr. Wacholder is a Fellow of the American Statistical Association an elected member of American Epidemiological Society. He is a statistical collaborator on genome-wide association studies of several cancers; on a trial of a vaccine to prevent infection with human papillomavirus (HPV); on projects investigating the natural history of HPV infection and cervical neoplasia; and studies of occupational exposure to benzene and to diesel. He has major methodologic publications in the areas of control selection for case-control studies; kin-cohort analysis, which he invented for the Washington Ashkenazi Study; population stratification in association studies of the effects of genetic variants; and a formal method for incorporating external information in a tests of hypothesis. He is editor emeritus of Epidemiology, senior editor for statistical methods and models at Cancer Epidemiology Biomarkers and Prevention, statistical editor at JNCI and associate editor at American Journal of Epidemiology.

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

• Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. "Human papillomavirus and cervical cancer." Lancet 2007; 370:890-907.
• Wacholder S. "The Impact of a Prevention Effort on the Community." Epidemiology 2005; 16:1-3.
• Wacholder S, Chanock S, Garcia-Closas M, El ghormli M, Rothman N. "Assessing the Probability That a Positive Report is False: An Approach for Molecular Epidemiology Studies." J Natl Cancer Inst 2004;96:434–42.
• Wacholder S, Rothman N, Caporaso N. "Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias." J Natl Cancer Inst 2000;92:1151-8.
• Wacholder S, McLaughlin JK, Silverman DT, Mandel JS. "Selection of controls in case-control studies. I. Principles. II. Types of controls. III. Design options." Am J Epidemiol 1992;135:1019-50.
• Wacholder S, et al. "The kin-cohort study for estimating penetrance." Am J Epidemiol 1998; 148:623-630.

Collaborators

DCEG Collaborators

• Neil Caporaso, M.D., Stephen Chanock, Patricia Hartge, Sc.D., Alan Hildesheim, Ph.D., Mark Schiffman, M.D., Debra Silverman, PhD, Margaret Tucker, M.D.

Other NCI Collaborators

• Douglas Lowy, Ph.D., John Schiller, Ph.D., Diane Solomon, M.D.

Other NIH Collaborators

• Clarice R. Weinberg, Ph.D., National Institute of Environmental Health Sciences

Other Scientific Collaborators

• David Hunter. M.D., Harvard University
• Muin J. Khoury, Centers for Disease Control