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Department of Epidemiology School of Public Health University of California, Los Angeles Spring, 2008 Molecular Epidemiology of Cancer EPI 243 (4 Units) Tuesday and Thursday 10:00 AM-11:50 A.M., 71-257 CHS Instructor: Zuo-Feng Zhang, M.D., Ph.D. Professor Office: 71-225 CHS Telephone: 825-8418 Fax: 206-6039 E-mail: [email protected] Office Hour: Thursday 12-2, or by appointment. 4/1 (wk 1.1) Introduction - Course outline and requirements Overview of the basic concepts of molecular epidemiology 4/3 (wk 1.2) Molecular Markers of exposures -Issues of the using adducts in epidemiologic studies -Methods of Detection -Protein adducts -DNA adducts -Serum/plasma concentration Summary of Molecular Epidemiology 4/8 (wk 2.1) Molecular Markers of Early Biological Response Oncogenes and Tumor Suppressor Genes -Discovery of oncogenes and tumor suppressor gene -Mechanisms of oncogene and tumor suppressor gene formation -Methods of Detection -Function of oncogenes and tumor suppressor genes -Oncogene/tumor suppressor genes and Epidemiologic Studies 4/10 (wk 2.2) Molecular Markers of susceptibility -Potentially useful susceptibility markers -Methods of Detection -Phase I enzymes and genes (p450th) -Phase II enzymes and genes (GST=s) -NAT 1 and 2 4/15 (wk 3.1) Molecular Biology in Epidemiology Dr. Jianyu Rao, Associate Professor of Pathology and Epidemiology -Introduction -Basic Principles of Molecular Biology -Core Techniques of Molecular Biology -Application 4/17 (wk 3.2) Design Considerations in Molecular Epidemiology (1) -Introduction -Using biomarkers in Epidemiological Research -Molecular Epidemiologic Study Designs 4/22 (wk 4.1) Design Considerations in Molecular Epidemiology (2) -Power estimate -Interaction assessment -Case-Case approach for interaction 4/24 (wk 4.2) Design Consideration: Biologic Specimen Collection, Process, Transportation and Banking -Utility of a bank for molecular epidemiologic studies -Major influence on the utility of biologic banks -Bias in studies involved banked materials 4/29 (wk 5.1) Design Consideration: Selection and Evaluation of Molecular Markers -Properties of Markers -Sate of Testing Validation of Molecular Markers -Measurement validity -Internal Validity -External Validity Some Practical Considerations for Planning Genetic Association Studies Based on TagSNPs Shehnaz K. Hussain, Ph.D., Sc.M. UCLA Division of Cancer Prevention and Control Research, School of Public Health and Jonsson Comprehensive Cancer Center 5/1 (wk 5.2) Applications: Intermediate Markers in Chemoprevention Jian-Yu Rao, MD 5/6 (wk 6.1) Applications: Susceptibility Markers in Cancer Epidemiology Zuo-Feng Zhang, MD, PhD 5/8 (wk 6.2) Applications: Exposure Markers in Cancer Epidemiology Binh Yang 5/13 (wk 7.1) New Technology: High-throughput SNP Identification Jeanette Papp, Ph.D. Assistant Adjunct Professor Director, Sequencing and Genotyping Core Department of Human Genetics 5/15 (wk 7.2) Summary of Molecular Epidemiology of Cancer Zuo-Feng Zhang, MD, PhD 5/20 (wk 8.1) Final Examination 5/22 (wk 8.2) Molecular Epidemiology Lab (1) (1) Collection of Buccal Cells (10-15 minutes) (2) Centrifuge Buccal Samples (3) Use of Pipette (4) Sample digestion 5/27 (wk 9.1) Molecular Epidemiology Lab (2) (1) extract DNA – Part I (2) leave in freezer 5/29 (wk 9.2) Molecular Epidemiology Lab (3) (1) extract DNA – Part II 6/3 (wk 10.1) Molecular Epidemiology Lab (4) (1) set up for PCR – GST M1, T1, beta-globin (2) PCR Amplification 6/5 (wk 10.2) Molecular Epidemiology Lab (5) (1) load gel eletrophoresis (2) run gel, get picture of gel Course Grade Participation Lab Final: Letter grade: 10% 35% 55% S/U 10% 35% 55% For the letter grade, A, B, or C will be assigned according to percentiles and the distribution curves of the scores by students. Each week, 1-3 readings for next lecture will be handed out. Students will be expected to read these papers. Course Description To introduce students to basic concept in molecular epidemiology of cancer, including molecular biology in epidemiology, selection, evaluation, and validation of biological markers, Design considerations statistical methods in molecular epidemiology. We will discuss practical issues such as biologic specimen collection, transportation, process and banking. The measurements and methodological issues of three major biological markers including exposure marker, susceptibility markers, and earlier biological response markers will be discussed. To introduce basic concepts and methodology of molecular epidemiology of cancer, and to review current molecular epidemiologic research of cancer in recent medical and epidemiological literature. S/U or letter grade. Suggested Text Books for Epidemiology 243: 1. Schulte PA and Perera FP. Molecular Epidemiology. Academic Press, Inc., New York, 1993, 3-44. 2. Hulka BS, Wilcosky TC, Griffith JD (Eds). Biological Markers in Epidemiology. Oxford University Press, New York, 1990 3. Franks LM & Teich NM (Editors): Introduction to the cellular & molecular biology of cancer. Oxford University Press, Oxford, 1998. 4.Toniolo P, Boffetta P, Shuker D, Rothman N, Hulka B and Pearce N (eds): Application of biomarkers to cancer epidemiology. International Agency for Research on Cancer (IARC) Scientific Publication No. 142, 1997.