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20.102

Macroepidemiology (BE.102)

Undergraduate · Historical course

Spring 2005

Topics

  • Introduction: Dimensions of information available to define the unknown causes of common diseases
  • Public health records and estimation of age-specific risk
  • Initiation
  • Promotion and Progression
  • Multiparametric Analysis of Colon Cancer
  • Multiparametric Analysis of Lung Cancer
  • Role of Gender
  • Sub-populations at Risk
  • National Risk and Community Risk
  • Familial Risk Expectations
  • Familial Risk Observations
  • Population Genetics
  • Population Genetics (cont.)
  • The search for genes carrying mutations conferring risk for common diseases
  • The search for genes carrying mutations conferring risk for common diseases (cont.)
  • The search for genes in which mutations of initiation (and promotion, if any) occur in common human cancers
  • The origins of somatic and inherited mutations in humans
  • The origins of somatic and inherited mutations in humans (cont.)
  • Hypotheses that need testing
  • General discussion and student presentations

Readings

  • Nordling, C. O. “A New Theory on Cancer-Inducing Mechanism.” Br J Cancer 7, no. 1 (Mar 1953): 68-72.
    Listed reading
  • ———. “Theories and statistics of cancer.” Nord Med. 47, no. 24 (Jun 13, 1952): 817-20.
    Listed reading
  • **Armitage, P., and R. Doll. “The Age Distribution of Cancer and a Multi-Stage Theory of Carcinogenesis.” Br J Cancer 8, no. 1 (Mar 1954): 1-12.
    Listed reading
  • **———. “A Two-Stage Theory of Carcinogenesis in Relation to the Age Distribution of Human Cancer.” Br J Cancer 11, no. 2 (Jun 1957): 161-9.
    Listed reading
  • ———. “The Age Distribution of Cancer and a Multi-Stage Theory of Carcinogenesis.” Br J Cancer 91, no. 12 (Dec 13, 2004A): 1983-9.
    Listed reading
  • **———. “The Age distribution of Cancer and a Multi-Stage Theory of Carcinogenosis.” Int J Epidemiol 33, no. 6 (Dec 2004B): 1174-9. Epub Aug 19, 2004.
    Listed reading
  • Moolgavkar, S. H., and A. G. Knudson, Jr. “Mutation and Cancer: A Model for Human Carcinogenesis.” J Natl Cancer Inst 66, no. 6 (Jun 1981): 1037-52.
    Listed reading
  • **Stein, W.D. “Analysis of cancer incidence data on the basis of multistage and clonal growth models.” Adv. Cancer Res. 56 (1991): 161-213.
    Listed reading
  • **Herrero-Jimenez, P., G. Thilly, P. J. Southam, A. Tomita-Mitchell, S. Morgenthaler, E. E. Furth, and W. G. Thilly. “Mutation, Cell Kinetics, and Subpopulations at Risk for Colon Cancer in the United States.” Mutat Res 400, nos. 1-2 (May 25, 1998): 553-78.
    Listed reading
  • **Herrero-Jimenez, P., A. Tomita-Mitchell, E. E. Furth, S. Morgenthaler, and W. G. Thilly. “Population Risk and Physiological Rate Parameters for Colon Cancer. The Union of an Explicit Model for Carcinogenesis with the Public Health Records of the United States.” Mutat Res 447, no. 1 (Jan 17, 2000): 73-116.
    Listed reading
  • Morgenthaler, S., P. Herrero, and W. G. Thilly. “Multistage Carcinogenesis and the Fraction at Risk.” J Math Biol 49, no. 5 (Nov 2004): 455-67.
    Listed reading
  • **Vatland, J. A. “Analysis of Community Cancer Mortality Rates.” Ph.D Thesis, MIT, September 2001.
    Listed reading
  • Hemminki, K., and B. Chen. “Familial Risk for Colorectal Cancers Are Mainly Due to Heritable Causes Cancer Epidemiology.” Biomarkers and Prevention 13 (2004A): 1253-1256.
    Listed reading
  • **———. “Familial Association of Colorectal Adenocarcinoma With Cancers at Other Sites.” Eur J Cancer 40, no. 16 (Nov 2004B): 2480-7.
    Listed reading
  • Hemminki, K., and K. Czene. “Attributable Risks of Familial Cancer from the Family-Cancer Database.” Cancer Epidemiol Biomarkers Prev 11, no. 12 (Dec 2002): 1638-44.
    Listed reading
  • Hemminki, K., and X. Li. “Familial and Second Primary Pancreatic Cancers: A Nationwide Epidemiologic Study from Sweden.” Int J Cancer 103, no. 4 (Feb 10, 2003): 525-30.
    Listed reading
  • ———. “Related Familial colorectal denocarcinoma from the Swedish Family-Cancer Database.” Int J Cancer 94, no. 5 (Dec 1, 2001A): 743-8.
    Listed reading
  • ———. “Increased Cancer Risk in the Offspring of Women with Colorectal Carcinoma. A Swedish Register-Based Cohort Study.” Cancer 91, no. 5 (Mar 1, 2001B): 1061-3.
    Listed reading
  • **Hemminki, K., I. Lonnstedt, P. Vaittinen, and P. Lichtenstein. “Estimation of Genetic and Environmental Components in Colorectal and Lung Cancer and Melanoma.” Genet Epidemiol 20, no. 1 (Jan 2001): 107-116.
    Listed reading
  • **Lichtenstein, P., N. V. Holm, P. K. Verkasalo, A. Iliadou, J. Kaprio, M. Koskenvuo, E. Pukkala, A. Skytthe, and K. Hemminki. “Environmental and Heritable Factors in the Causation of Cancer - Analyses of Cohorts of Twins from Sweden, Denmark, and Finland.” N Engl J Med 343, no. 2 (Jul 13, 2000): 78-85.
    Listed reading
  • Calvari-Sforza, L. L., and W. F. Bodmer. The Genetics of Human Populations . San Francisco: W. H. Freeman, 1971.
    Listed reading
  • Calvari-Sforza, L. L., P. Menozzi, and A. Piazza. The History and Geography of Human Genes . Princeton: Princeton University Press, 1994.
    Listed reading
  • Hartl, D. L. A Primer of Population Genetics . 3rd ed. Sunderland, MA: Sinauer, 2000.
    Listed reading
  • Vogel, F., and R. Rathenberg. “Spontaneous Mutation in Man.” Adv Hum Genet 5 (1975): 223-318.
    Listed reading
  • Lander, E. S., and D. Botstein. “Mapping Complex Genetic Traits in Humans: New Methods Using a Complete RFLP Linkage Map.” Cold Spring Harb Symp Quant Biol 51, Part 1 (1986): 49-62.
    Listed reading
  • **———. “Mapping Mendelian Factors Underlying Quantitative Traits Using RFLP Linkage Maps.” Genetics 121, no. 1 (Jan 1989): 185-99. [Erratum in: Genetics 136, no. 2 (Feb 1994): 705.]
    Listed reading
  • **Tomita-Mitchell, A., B. P. Muniappan, P. Herrero-Jimenez, H. Zarbl, and W. G. Thilly. “Single Nucleotide Polymorphism Spectra in Newborns and Centenarians: Identification of Genes Coding for Risk of Mortal Disease.” Gene 223, no. 1-2 (Nov 26, 1998): 381-91.
    Listed reading
  • Li-Sucholeiki, X. C., and W. G. Thilly. “A Sensitive Scanning Technology for Low Frequency Nuclear Point Mutations in Human Genomic DNA.” Nucleic Acids Res 28, no. 9 (May 1, 2000): E44.
    Listed reading
  • **Hirschhorn, J. N., K. Lohmueller, E. Byrne, and K. Hirschhorn. “A Comprehensive Review of Genetic Association Studies.” Genet Med 4, no. 2 (Mar-Apr 2002): 45-61.
    Listed reading
  • Nunney, L. “The Population Genetics of Multistage Carcinogenesis.” Proc R Soc Lond B Biol Sci 270, no. 1520 (Jun 7, 2003): 1183-91.
    Listed reading
  • **Morgenthaler, S., and W. G. Thilly. Pangenomic Search for Genetic Risks for Common Diseases, 2005. (Manuscript in preparation.)
    Listed reading
  • Scientific American , September 1996. Special issue on ideas on origins of cancer.
    Listed reading
  • **Wynder, E. L., E. A. Graham. “Tobacco Smoking as a Possible Etiologic Factor in Bronchiogenic Carcinoma; A Study of 684 Proved Cases.” J Am Med Assoc 143, no. 4 (May 27, 1950): 329-36.
    Listed reading
  • Armitage, P., et al. “Dose-Response Relationship in Radiation Leukaemia.” Nature 184, Supplement 21 (Nov 21, 1959): 1669-70.
    Listed reading
  • **Thilly, W. G. “Have Environmental Mutagens Caused Oncomutations in People?” Nature Genetics 34 (2003): 255-259.
    Listed reading
  • Wogan, G. N., S. S. Hecht, J. S. Felton, A. H. Conney, and L. A. Loeb. “Environmental and Chemical Carcinogenesis.” Semin Cancer Biol 14, no. 6 (Dec 2004): 473-86.
    Listed reading
  • Chan, A .T., E. L. Giovannucci, E. S. Schernhammer, G. A. Colditz, D. J. Hunter, W. C. Willett, and C. S. Fuchs. “A Prospective Study of Aspirin use and the Risk for Colorectal Adenoma.” Ann Intern Med 140, no. 3 (Feb 3, 2004): 157-66.
    Listed reading
  • **Trichopoulos, D., F. P. Li, and D. J. Hunter. “What Causes Cancer?” Sci Am 275, no. 3 (Sep 1996): 80-7.
    Listed reading
  • Harris, D. M., and V. L. Go. “Vitamin D and Colon Carcinogenesis.” J Nutr 134, no. 12 Supplement (Dec 2004): 3463S-3471S.
    Listed reading
  • Whelan, J., and M. F. McEntee. “Dietary (n-6) PUFA and Intestinal Tumorigenesis.” J Nutr 134, no. 12 Supplement (Dec 2004): 3421S-3426S.
    Listed reading
  • Hung, H. C., K. J. Joshipura, R. Jiang, F. B. Hu, D. Hunter, S. A. Smith-Warner, G. A. Colditz, B. Rosner, D. Spiegelman, and W. C. Willett. “Fruit and Vegetable Intake and Risk of Major Chronic Disease.” J Natl Cancer Inst 96, no. 21 (Nov 3, 2004): 1577-84.
    Listed reading
  • Cohnheim, J. “Ueber Entzundung und Eiterung.” Path Anat Physiol Klin Med 40 (1867): 1-79.
    Listed reading
  • **Sell, S. “Stem Cell Origin of Cancer and Differentiation Therapy.” Crit Rev Oncol Hematol 51, no. 1 (Jul 2004): 1-28.
    Listed reading
  • **Gostjeva, E. V., L. Zukerberg, D. Chung, and W. G. Thilly. Nuclear Morphotypes and Metamorphoses in Human Colonic Ontogenesis and Carcinogenesis. (2005) Manuscript submitted.
    Listed reading
  • Boveri, T. Zur Frage der Entstehung maligner Tumoren. Fischer, Jena, 1914.
    Listed reading
  • ———. “The origin of malignant tumors.” Baltimore: Williams Wilkins, 1929.
    Listed reading
  • **Balmain, A. “Cancer Genetics: From Boveri and Mendel to Microarrays.” Nat Rev Cancer 1 (2001): 77-82.
    Listed reading
  • Temin, H. M. “The Protovirus Hypothesis: Speculations on the Significance of RNA-Directed DNA Synthesis for Normal Development and for Carcinogenesis.” J Natl Cancer Inst 46, no. 2 (Feb 1971): 3-7.
    Listed reading
  • Mitelman, F., B. Johansson, and F. Mertens. Catalog of Chromosome Aberrations in Cancer . 5th ed. CD-ROM version with annual updates. New York: Wiley, 1998.
    Listed reading
  • Listed reading
  • Knudson, A. G., Jr. “Mutation and Cancer: Statistical Study of Retinoblastoma.” Proc Natl Acad Sci U S A 68, no. 4 (Apr 1971): 820-3.
    Listed reading
  • Groden, J., A. Thliveris, W. Samowitz, M. Carlson, L. Gelbert, H. Albertsen, G. Joslyn, J. Stevens, L. Spirio, and M. Robertson, et al. “Identification and Characterization of the Familial Adenomatous Polyposis Coli Gene.” Cell. 66, no. 3 (Aug 9, 1991): 589-600.
    Listed reading
  • **Knudson, A. G. “Cancer Genetics.” Am J Med Genet 111, no. 1 (Jul 22, 2002): 96-102.
    Listed reading
  • Weinberg, R. A. “How Cancer Arises.” Sci Am 275, no. 3 (Sep 1996): 62-70.
    Listed reading
  • **Rangarajan, A., S. J. Hong, A. Gifford, and R. A. Weinberg. “Species- and Cell Type-specific Requirements for Cellular Transformation.” Cancer Cell 6, no. 2 (Aug 2004): 171-83.
    Listed reading
  • Keohavong, P., and W. G. Thilly. “Fidelity of DNA Polymerases in DNA Amplification.” Proc Natl Acad Sci U S A 86, no. 23 (Dec 1989): 9253-7.
    Listed reading
  • **Loeb, L. A., and K. C. Cheng. “Errors in DNA Synthesis: A Source of Spontaneous Mutations.” Mutat Res 238, no. 3 (May 1990): 297-304.
    Listed reading
  • **Khrapko, K., H. A. Coller, P. C. Andre, X. C. Li, J. S. Hanekamp, and W. G. Thilly. “Mitochondrial Mutational Spectra in Human Cells and Tissues.” Proc Natl Acad Sci U S A 94, no. 25 (Dec 9, 1997A): 13798-803.
    Listed reading
  • **Coller, H. A., K. Khrapko, A. Torres, M. W. Frampton, M. J. Utell, and W. G. Thilly. “Mutational Spectra of a 100-base Pair Mitochondrial DNA Target Sequence in Bronchial Epithelial Cells: A Comparison of Smoking and Nonsmoking Twins.” Cancer Res 58, no. 6 (Mar 15, 1998): 1268-77.
    Listed reading
  • **Muniappan, B. P., and W. G. Thilly. “The DNA Polymerase Beta Replication Error Spectrum in the Adenomatous Polyposis Coli Gene contains Human Colon Tumor Mutational Hotspots.” Cancer Res 62, no. 11 (Jun 1, 2002): 3271-5.
    Listed reading
  • Coller, H. A., K. Khrapko, N. D. Bodyak, E. Nekhaeva, P. Herrero-Jimenez, and W. G. Thilly. “High Frequency of Homoplasmic Mitochondrial DNA Mutations in Human Tumors can be Explained Without Selection.” Nat Genet 28, no. 2 (Jun 2001): 147-50.
    Listed reading
  • Zheng, W. M., K. Khrapko, H. Coller, W. G. Thilly, and W. Copeland. The Gamma DNA Polymerase Replication Error Spectrum Contains Human Tissue Mitochondrial Hotspots. (Manuscript draft, 2005)
    Listed reading
  • Tomita-Mitchell, A., L. L. Ling, C. L. Glover, J. Goodluck-Griffith, and W. G. Thilly. “The Mutational Spectrum of the HPRT Gene from Human T Cells in Vivo Shares a Significant Concordant Set of Hot Spots with MNNG-treated Human Cells.” Cancer Res 63, no. 18 (Sep 15, 2003): 5793-8.
    Listed reading
  • Thilly, W. G. “Have Environmental Mutagens Caused Onco Mutations in People?” Nature Genetics 34 (2003): 255-259.
    Listed reading
  • **Benzer, S. “The Fine Structure of the Gene.” Sci Am 206 (Jan 1962): 70-84.
    Listed reading
  • Nomura, M., and S. Benzer. “The Nature of the “Deletion” Mutants in the rII Region of Phage T4.” J Mol Biol 3 (Oct 1961): 684-92.
    Listed reading
  • Benzer, S. “Genetic Fine Structure.” Harvey Lect 56 (1960-1961): 1-21.
    Listed reading
  • Brenner, S., S. Benzer, and L. Barnett. “Distribution of Proflavin-induced Mutations in the Genetic Fine Structure.” Nature 182, no. 4641 (Oct 11, 1958): 983-5.
    Listed reading
  • Benzer, S. “Genetic Fine Structure and its Relation to the DNA Molecule.” Brookhaven Symp Biol 8 (Feb 1956): 3-5.
    Listed reading
  • Khrapko, K., P. Andre, R. Cha, G. Hu, and W. G. Thilly. “Mutational Spectrometry: Means and Ends.” Prog Nucleic Acid Res Mol Biol 49 (1994A): 285-312.
    Listed reading
  • Khrapko, K., J. S. Hanekamp, W. G. Thilly, A. Belenkii, F. Foret, and B. L. Karger. “Constant Denaturant Capillary Electrophoresis (CDCE): A High Resolution Approach to Mutational Analysis.” Nucleic Acids Res 22, no. 3 (Feb 11, 1994B): 364-9.
    Listed reading
  • Khrapko, K., H. Coller, P. Andre, X. C. Li, F. Foret, A. Belenky, B. L. Karger, and W. G. Thilly. “Mutational Spectrometry Without Phenotypic Selection: Human Mitochondrial DNA.” Nucleic Acids Res 25, no. 4 (Feb 15, 1997B): 685-93.
    Listed reading
  • Andre, P., A. Kim, K. Khrapko, and W. G. Thilly. “Fidelity and Mutational Spectrum of Pfu DNA Polymerase on a Human Mitochondrial DNA Sequence.” Genome Res 7, no. 8 (Aug 1997): 843-52.
    Listed reading
  • Khrapko, K., H. A. Coller, X. C. Li-Sucholeiki, P. C. Andre, and W. G. Thilly. “High Resolution Analysis of Point Mutations by Constant Denaturant Capillary Electrophoresis (CDCE).” Methods Mol Biol 163 (2001): 57-72.
    Listed reading
  • Ekstrom, P. O., J. Bjorheim, G. Gaudernack, and K. E. Giercksky. “Population Screening of Single-nucleotide Polymorphisms Exemplified by Analysis of 8000 Alleles.” J Biomol Screen 7, no. 6 (Dec 2002): 501-6.
    Listed reading
  • Minarik, M., L. Minarikova, J. Bjorheim, and P. O. Ekstrom. “Cycling Gradient Capillary Electrophoresis: A Low-cost Tool for High-throughput Analysis of Genetic Variations.” Electrophoresis 24, no. 11 (Jun 2003): 1716-22.
    Listed reading
  • **Bjorheim, J., T. W. Abrahamsen, A. T. Kristensen, G. Gaudernack, and P. O. Ekstrom. “Approach to Analysis of Single Nucleotide Polymorphisms by Automated Constant Denaturant Capillary Electrophoresis.” Mutat Res 526, no. 1-2 (May 15, 2003): 75-83.
    Listed reading
  • Luria, S. E. “Mutation of Bacterial Viruses Affecting their Host Range.” Genetics 30 (1945): 84-99.
    Listed reading
  • Leung, E. S. “A Modified Method for the 1000-compartment Fluctuation Test.” Heredity 33, no. 3 (Dec 1974): 417-9.
    Listed reading
  • In lieu of a textbook, the class will read approximately 30 manuscripts from a larger set of recommended readings.
    Listed reading
Sources