Biography

Dr. Wacholder is a senior investigator in the Biostatistics Branch, Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), National Institutes of Health (NIH). He works as an applied statistician in the NIH Intramural Research Program.

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 and an elected member of the American Epidemiological Society.

Dr. Wacholder plays a major role in several DCEG-sponsored research areas. He has been the lead statistician in the very successful DCEG research program in human papillomavirus (HPV) and its consequences since the early 1990’s. He began working in genetic epidemiology with the Washington Ashkenazi Study, for which he invented kin-cohort analysis. He was a statistical initiator of the Cancer Genetic Markers of Susceptibility (CGEMS) from its inception, and a leader of the CGEMS genome-wide association (GWA) studies of cancers of the breast and the prostate. He maintains his interest in childhood cancers from his work on electromagnetic fields and childhood acute lymphocytic leukemia, and is now involved in GWAS of osteogenic sarcoma and Ewing sarcoma, rarer cancers that target adolescents and young adults. He is a collaborator on large, comprehensive case-control studies of lung cancer and renal cell cancer.

Dr. Wacholder has made major contributions to a variety of methodologic areas: design of case-control studies, including a series of papers on choosing controls; population stratification in association studies of the effects of genetic variants; and a formal method for evaluating the chance that a reported positive finding is a false positive by incorporating external information.

He is editor emeritus of Epidemiology, senior editor for statistical methods and models at Cancer Epidemiology Biomarkers and Prevention, statistical editor at JNCI and an associate editor at American Journal of Epidemiology.

Research Interests

Dr. Wacholder’s research agenda is driven by study design, analysis and interpretation issues facing scientists in DCEG and elsewhere who are trying to understand the causes of cancer and the means for its prevention. In addition, much of his independent and collaborative work involves molecular epidemiology. In both substantive and methodological work, he focuses on:

• How to frame the most important research questions, and then design efficient studies and plan rigorous analyses to make progress in addressing the questions?
• How to reduce error from bias, random variation and misinterpretation of studies?
• How to translate results of studies to prevent disease or mitigate the effects of disease?

Collaboration in Epidemiologic Studies

Dr. Wacholder is the statistician for a randomized controlled trial of HPV bivalent HPV vaccine against HPV infection and cervical intaepithelial neoplasia , funded by NCI. In response to a request from the Data Safety Monitoring Board, he recently investigated the effect of vaccine on risk of miscarriage.

Dr. Wacholder plays a major role in several cohort studies with longitudinal collection of specimens. These molecular epidemiology studies have clarified the natural history of HPV infection and form the basis of evolving clinical guidelines for cervical cancer prevention in the high- and low-resource regions.

Dr. Wacholder recently led an analysis evaluating the performance of traditional risk factors and newly discovered genetic variants as predictors of breast cancer risk.

In his collaborative work, Dr. Wacholder is involved in decisions about whether a study should be initiated, its basic design, selection of study participants, and assessment of exposure and disease. He also focuses on other statistical and methodologic issues, such as quality control and other fieldwork issues, the analytic plan and specific analyses, interpretation of results, and preparation of publications.

Design of Epidemiologic Studies

Dr. Wacholder continues to consider questions about how to use cohorts effectively and efficiently, and when case-control studies are needed, especially in molecular and genetic epidemiology.

Molecular Epidemiology

Dr. Wacholder has been involved in methodologic aspects of all phases of molecular epidemiology work, including biomarker development and validation, assessment of impact of misclassification of markers, design and analysis of longitudinal studies assessing the effect of changing biomarker levels and use of molecular rather than clinical endpoints in trials.

Translation from epidemiologic data to clinic management and prevention

Dr. Wacholder’s research on HPV raises and starts to address formidable clinical and prevention questions about vaccination policy and appropriate programs for cervical screening. HPV is the best cancer biomarker, causing nearly all cervical cancer, yet the high prevalence of infection with oncogenic HPV in women who will never develop disease types raises new challenges. Translation of the new information from large-scale genetic epidemiology studies to screening or other prevention programs is another area of interest.

Keywords

study design, case-control studies, control selection; epidemiologic methods, statistical methods, genetic epidemiology, molecular epidemiology, gene-environment interaction; human papillomavirus; natural history; translation; genome wide association studies

Selected Publications

• Wacholder S, Chen BE, Wilcox A, Macones G, Gonzalez P, Befano B, Hildesheim A, Rodríguez AC, Solomon D, Herrero R, Schiffman M for the CVT group. Risk of miscarriage in two randomized controlled trials of a bivalent vaccine against human papillomavirus types 16 and 18. British Medical Journal. 2010 Mar 2; 340:c712.
• Wacholder S, Hartge P, Prentice R, Garcia-Closas M, Feigelson HS, Diver WR, Thun MJ, Cox DG, Hankinson SE, Kraft P, Rosner B, Berg CD, Brinton LA, Lissowska J, Sherman ME, Chlebowski R, Kooperberg C, Jackson RD, Buckman DW, Hui P, Pfeiffer R, Jacobs KB, Thomas GD, Hoover RN, Gail MH, Chanock SJ, Hunter DJ. Performance of common genetic variants in breast-cancer risk models. N Engl J Med. 2010 Mar 18;362(11):986-93.
• Yeager M, Chatterjee N, Ciampa J, Jacobs KB, Gonzalez-Bosquet J, Hayes RB, Kraft P, Wacholder S, Orr N, Berndt S, Yu K, Hutchinson A, Wang Z, Amundadottir L, Feigelson HS, Thun MJ, Diver WR, Albanes D, Virtamo J, Weinstein S, Schumacher FR, Cancel-Tassin G, Cussenot O, Valeri A, Andriole GL, Crawford ED, Haiman CA, Henderson B, Kolonel L, Le Marchand L, Siddiq A, Riboli E, Key TJ, Kaaks R, Isaacs W, Isaacs S, Wiley KE, Gronberg H, Wiklund F, Stattin P, Xu J, Zheng SL, Sun J, Vatten LJ, Hveem K, Kumle M, Tucker M, Gerhard DS, Hoover RN, Fraumeni JF Jr, Hunter DJ, Thomas G, Chanock SJ. Identification of new prostate cancer susceptibility locus on chromosome 8q24. Nat Genet. 2009 Oct; 41(10):1055-7.
• Wacholder S. Bias in full cohort and nested case-control studies? Epidemiology. 2009 May; 20(3):339-40.
• 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, Hartge P, Struewing JP, Pee D, McAdams M, Brody L, Tucker M. The kin-cohort study for estimating penetrance. Am J Epidemiol 1998; 148:623-630.
• Hayes RB, Yin SN, Dosemeci M, Li GL, Wacholder S, Travis LB, Li CY, Rothman N, Hoover RN, Linet MS for the CAPM-NCI Benzene Study Group. Benzene and the dose-related incidence of hematologic neoplasms in China. J Natl Cancer Inst 1997; 89:1065-71.
• Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC, Tucker MA. The risk of cancer associated specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997; 336:1401-8.
• 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.

Collaborators

Direct Mentorees

• Kai Yu, PhD; Hormuzd Katki, PhD; Arpita Ghosh, PhD

Direct Mentorees

• Neil Caporaso, M.D., Philip Castle, PhD; Stephen Chanock. M.D.; Nilanjan Chatterjee, PhD; Patricia Hartge, Sc.D.; Alan Hildesheim, Ph.D.; Robert Hoover, M.D., ScD; Hormuzd Katki, PhD; Aimee Kreimer, PhD; Maria-Teresa Landi, M.D.; Mahboobeh Safaeian, PhD, Mark Schiffman, M.D.; Sharon Savage, M.D.; Debra Silverman, PhD; Margaret Tucker, M.D.; Nicholas Wentzensen, M.D.; Kai Yu. PhD

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

• Robert Burk, Albert Einstein School of Medicine, Bronx, NY
• Rolando Herrero, M.D., INCIENSA, San Juan, Costa Rica
• Muin J. Khoury, Centers for Disease Control
• Ana Cecilia Rodriguez, M.D., INCIENSA, San Juan, Costa Rica