DCEG Mourns Biostatistician and Mentor Sholom Wacholder

October 5, 2015, by DCEG Staff

Sholom Wacholder, Ph.D. died October 4, 2015, at his home in Rockville, Maryland.

"Dr. Wacholder made tremendous contributions to the fields of cancer epidemiology and biostatistics as well as to his community of colleagues at NCI and to those whom he mentored," said Stephen Chanock, M.D., Division Director. "He will be greatly missed by all of us. He was a special colleague and friend to so many."

Dr. Wacholder leaves behind a legacy of research excellence in genetic epidemiology that is both diverse and remarkably deep. A statistician by training, he was sought out by colleagues across the Division to advise on critical methodological and analytic components of nearly all major undertakings of the Division over the past 30 years, exploring the causes of cancer from natural history studies through clinical trials. He had a keen sense of the underlying biological questions and succeeded in helping the rest of us to become smarter and better informed. His breadth ranged from studies of risk factors to the application of new technologies to investigate the heritable component of different cancers.

Human Papillomavirus

He was the lead statistician for the NCI study of the natural history of human papillomavirus (HPV) and cancer, culminating in the launch and successful completion of the NCI Costa Rica HPV Vaccine Trial. Dr. Wacholder spoke about his contributions to this body of work in a video titled "In their own words: Dr. Sholom Wacholder," completed in 2010.

Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia.
Schiffman MH, Bauer HM, Hoover RN, Glass AG, Cadell DM, Rush BB, Scott DR, Sherman ME, Kurman RJ, Wacholder S, et al. J Natl Cancer Inst 1993 Jun 16;85:958-964.
Risk of miscarriage with bivalent vaccine against human papillomavirus (HPV) types 16 and 18: Pooled analysis of two randomised controlled trials.
Wacholder S, Chen BE, Wilcox A, Macones G, Gonzalez P, Befano B, Hildesheim A, Rodríguez AC, Solomon D, Herrero R, Schiffman M; CVT group. BMJ 2010 Mar 2;340:c712. doi: 10.1136/bmj.c712.
Proof-of-principle evaluation of the efficacy of fewer than three doses of a bivalent HPV16/18 vaccine.
Kreimer AR, Rodriguez AC, Hildesheim A, Herrero R, Porras C, Schiffman M, González P, Solomon D, Jiménez S, Schiller JT, Lowy DR, Quint W, Sherman ME, Schussler J, Wacholder S; CVT Vaccine Group. J Natl Cancer Inst 2011 Oct 5;103:1444-1451. Epub 2011 Sep 9.

Genetics

Dr. Wacholder began working in genetic epidemiology with the Washington Ashkenazi Study, and was one of the first to develop kin-cohort analysis, a novel sampling approach to eliminate statistical bias from studies of genetically similar populations. He was a key statistical consultant and analyst of the Cancer Genetic Markers of Susceptibility (CGEMS) project from its inception, thereby laying the foundation for the many disease-specific genome-wide association studies conducted over the past decade.

The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews.
Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC, Tucker MA. N Engl J Med 1997 May 15;336:1401-1408.
The kin-cohort study for estimating penetrance.
Wacholder S, Hartge P, Struewing JP, Pee D, McAdams M, Brody L, Tucker M. Am J Epidemiol 1998 Oct 1;148:623-630.
Population stratification in epidemiologic studies of common genetic variants and cancer: Quantification of bias.
Wacholder S, Rothman N, Caporaso N. J Natl Cancer Inst 2000 Jul 19;92:1151-1158.

His interest in childhood cancers led him to research on electromagnetic fields and childhood acute lymphocytic leukemia, and later to pursue the inheritance of osteogenic sarcoma, a cancer that targets adolescents and young adults. He was also a key collaborator on large, comprehensive case-control studies of lung cancer and renal cell cancer.

Methods

He made many major contributions to the methodologic rigor of the Division's work, including the following highlights: the design of case-control studies, including a series of papers on choosing controls; the contribution of underlying population substructure to error in association studies; and a formal method for evaluating the chance that a reported positive finding is a false positive by incorporating external information.

Selection of controls in case-control studies. I. Principles.
Wacholder S, McLaughlin JK, Silverman DT, Mandel JS. Am J Epidemiol 1992 May 1;135:1019-1028.
Assessing the probability that a positive report is false: An approach for molecular epidemiology studies.
Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N. J Natl Cancer Inst 2004 Mar 17;96:434-442.

Dr. Wacholder was a marvelous teacher. His capacity to carefully and thoughtfully construct arguments, usually based on his “first principles”, was boundless. His wisdom was sought by all in the Division, particularly in the design and analysis of new cancer epidemiology studies. He served as an enthusiastic mentor to countless doctoral and post-doctoral students, always generous with his time. In this, he emulated his father, a remarkable scholar and teacher. In eulogizing his father in 2011, Dr. Wacholder reflected on the elder’s imperative to “teach these words to your sons—every waking hour of every day;” the Judaic ‘mitzvah’ applies to teaching Torah, but in the Wacholder household—of both generations—this good and necessary deed extended to science, history, philosophy and math. Roaming the halls of DCEG or sequestered in his office surrounded by stacks of papers, Dr. Wacholder constantly sought to teach those around him, engaging his peers as well as support staff in debates over scientific and philosophical approaches to the work at hand.

Dr. Wacholder received a Ph.D. in biomathematics from the University of Washington in 1982. He was a Fellow of the American Statistical Association and an elected member of the American Epidemiological Society. He served on the editorial boards of numerous journals, including Epidemiology, Cancer Epidemiology Biomarkers and Prevention, Journal of the National Cancer Institute, and the American Journal of Epidemiology.

He is survived by his wife, Michelle, their two adult sons, Aaron and Jonah, his sisters and brother, and many nieces and nephews.