Designing and implementing quality control for multi-center screening of mutations in the ATM gene among women with breast cancer


  • Communicated by Albert de la Chapelle

  • WECARE Study Collaborative Group: Principal Investigator—J.L.B.; Co-Principal Investigators—W.D.T. (Chair of the Epidemiology and Biostatistics Core), R.W.H., L.B. (Chair of the Data Collection Core), P.J.C. (Chair of the Laboratory Core).

    Coordinating Center (Mount Sinai School of Medicine, NY): S.L.T. (Project Director), Gertrud S. Berkowitz (Epidemiologist), Xiaolin Liang (Informatics Specialist), Monica Katyal (Project Coordinator), Stephanie Skoler (Project Coordinator); National Cancer Institute: Daniela Seminara (Program Officer).

    Laboratories: Virginia Mason Research Center—S.T. (Laboratory Director), Eric Olson (Laboratory Manager); USC—A.T.D. (Laboratory Director), Nianmin Zhou (Laboratory Manager), Yong Liu (Director of Blood Processing); Norwegian Radium Hospital, Oslo, Norway—Anne-Lise Børresen-Dale (Laboratory Director), L.J. (Laboratory Manager); MSSM—B.S.R. (Laboratory Director), D.P.A. (Laboratory Manager); UCLA—R.A.G. (Consultant).

    Data Collection Centers: USC—Laura Donnelly (Project Manager), Maya Mahue-Giangreco (Project Manager); Danish Cancer Society, Copenhagen, Denmark—Jørgen H. Olsen (Director), Lene Mellemkjær (Project Manager); Fred Hutchinson Cancer Research Center, Seattle, WA—Kathleen E. Malone (Director), Noemi Epstein (Project Manager); UC Irvine—Hoda Anton-Culver (Director), Joan Largent (Project Manager); University of Iowa, Iowa City—Charles F. Lynch (Director), Jeanne DeWall (Project Manager).

    Radiation Core: University of Texas, MD Anderson Cancer Center, Houston—Marilyn Stovall (Dosimetry Laboratory Director and Chair, Radiation Core); New York University—Roy E. Shore (Epidemiologist); International Epidemiology Institute, Rockville and Vanderbilt University, Nashville, TN—John D. Boice Jr. (Consultant).

    Epidemiology and Biostatistics Core: USC—Duncan C. Thomas, Bryan M. Langholz.


Epidemiologic studies of breast and other cancers are increasingly turning toward large, multi-center designs in order to obtain adequate power to detect low-penetrance susceptibility alleles. The size of such studies often makes it necessary to distribute the genetic screening efforts to multiple sites. Careful standardization of screening methodology and quality control across sites is required for such multi-center screening designs to be efficient. In this report, we illustrate our approach to these challenges in the context of the WECARE (Women's Environment, Cancer and Radiation Epidemiology) Study, a multi-center population-based genetic epidemiologic study of women with unilateral and bilateral breast cancer. We provide optimized conditions for screening the ataxia-telangiectasia gene (ATM) for variation by denaturing high-performance liquid chromatography (DHPLC) and describe the results of two independent quality control studies at four international centers employing these conditions. Finally, we report novel mutations in the ATM gene identified both in patients with ataxia-telangiectasia and in patients with unilateral or bilateral breast cancer. Hum Mutat 21:542–550, 2003. © 2003 Wiley-Liss, Inc.