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JNCI Monographs 1999 1999(26):1-16;
© 1999 by Oxford University Press
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Journal of the National Cancer Institute Monographs, No. 26, 1-16, 1999
© 1999 Oxford University Press

I. GENE DISCOVERY PANEL

Discovery of Cancer Susceptibility Genes: Study Designs, Analytic Approaches, and Trends in Technology

Daniel J. Schaid, Ken Buetow, Daniel E. Weeks, Ellen Wijsman, Sun-Wei Guo, Jurg Ott, Carol Dahl

Affiliations of authors: D. J. Schaid, Departments of Health Sciences Research and Medical Genetics, Mayo Clinic/Mayo Foundation, Rochester, MN; K. Buetow, C. Dahl, National Cancer Institute, National Institutes of Health, Bethesda, MD; D. E. Weeks, Department of Human Genetics, University of Pittsburgh, PA; E. Wijsman, Medical Genetics and Biostatistics, University of Washington, Seattle; S.-W. Guo, Division of Epidemiology, University of Minnesota, Minneapolis; J. Ott, Rockefeller University, New York, NY.

Correspondence to: Daniel J. Schaid, Ph.D., Harwick 7, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 (e-mail: schaid{at}mayo.edu).

Determining the genetic causes of cancers has immense public health benefits, ranging from prevention to earlier detection and treatment of disease. Although a number of cancer susceptibility genes have been successfully identified, design and analytic issues remain that challenge the current paradigm of gene discovery. Some examples are the definition and measurement of cancer phenotype, the use of intermediate end points, the choice of sample (e.g., affected relative pairs versus large extended pedigrees), the choice of analytic method [e.g., parametric logarithm of the odds (LOD) score method versus model-free methods], and the influence of gene-environment interaction on linkage analysis. Furthermore, association methods, based on either the traditional case-control study design or family-based controls, are popular choices to evaluate candidate genes or screen for linkage disequilibrium. Finally, the study design and analytic methods for gene discovery are determined to some extent by what genomic technology is feasible within the laboratory. Many of the main issues related to gene discovery, as well as trends in genomic technology that will impact on gene discovery, are discussed from the perspective of their strengths and weaknesses, pointing to areas in need of further work.


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