20.102 | Spring 2005 | Undergraduate
Macroepidemiology (BE.102)

Readings

Assigned readings are preceded by asterisks**.

Public Health Records and Analysis

Annual Cancer Deaths and Population Sizes as a Function of Age in the United States (1890-1997) and Japan (1952-1995).

Prof. Thilly’s Mortality Data Page

Attempts to Fit Cancer Cascade Models to Age-specific Cancer Rates

Nordling, C. O. “A New Theory on Cancer-Inducing Mechanism.” Br J Cancer 7, no. 1 (Mar 1953): 68-72.

———. “Theories and statistics of cancer.” Nord Med. 47, no. 24 (Jun 13, 1952): 817-20.

**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.

**———. “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.

———. “The Age Distribution of Cancer and a Multi-Stage Theory of Carcinogenesis.” Br J Cancer 91, no. 12 (Dec 13, 2004A): 1983-9.

**———. “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.

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.

**Stein, W.D. “Analysis of cancer incidence data on the basis of multistage and clonal growth models.” Adv. Cancer Res. 56 (1991): 161-213.

**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.

**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.

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.

Population Genetics and Familial Risk

Community Risk

**Vatland, J. A. “Analysis of Community Cancer Mortality Rates.” Ph.D Thesis, MIT, September 2001.

Familial Risk: Parent/Child and Twins

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.

**———. “Familial Association of Colorectal Adenocarcinoma With Cancers at Other Sites.” Eur J Cancer 40, no. 16 (Nov 2004B): 2480-7.

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.

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.

———. “Related Familial colorectal denocarcinoma from the Swedish Family-Cancer Database.” Int J Cancer 94, no. 5 (Dec 1, 2001A): 743-8.

———. “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.

**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.

**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.

Population Genetics

Calvari-Sforza, L. L., and W. F. Bodmer. The Genetics of Human Populations. San Francisco: W. H. Freeman, 1971.

Calvari-Sforza, L. L., P. Menozzi, and A. Piazza. The History and Geography of Human Genes. Princeton: Princeton University Press, 1994.

Hartl, D. L. A Primer of  Population Genetics. 3rd ed. Sunderland, MA: Sinauer, 2000.

Vogel, F., and R. Rathenberg. “Spontaneous Mutation in Man.” Adv Hum Genet 5 (1975): 223-318.

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.

**———. “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.]

**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.

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.

**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.

Nunney, L. “The Population Genetics of Multistage Carcinogenesis.” Proc R Soc Lond B Biol Sci 270, no. 1520 (Jun 7, 2003): 1183-91.

**Morgenthaler, S., and W. G. Thilly. Pangenomic Search for Genetic Risks for Common Diseases, 2005. (Manuscript in preparation.)

Environmental Epidemiology

Scientific American, September 1996. Special issue on ideas on origins of cancer.

Chemicals and Radiation

**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.

Armitage, P., et al. “Dose-Response Relationship in Radiation Leukaemia.” Nature 184, Supplement 21 (Nov 21, 1959): 1669-70.

**Thilly, W. G. “Have Environmental Mutagens Caused Oncomutations in People?” Nature Genetics 34 (2003): 255-259.

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.

Inflammatory Conditions

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.

Nutrition

**Trichopoulos, D., F. P. Li, and D. J. Hunter. “What Causes Cancer?” Sci Am 275, no. 3 (Sep 1996): 80-7.

Harris, D. M., and V. L. Go. “Vitamin D and Colon Carcinogenesis.” J Nutr 134, no. 12 Supplement (Dec 2004): 3463S-3471S.

Whelan, J., and M. F. McEntee. “Dietary (n-6) PUFA and Intestinal Tumorigenesis.” J Nutr 134, no. 12 Supplement (Dec 2004): 3421S-3426S.

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.

Human Physiology and Genetics

Cancers as Embryos

Cohnheim, J. “Ueber Entzundung und Eiterung.” Path Anat Physiol Klin Med 40 (1867): 1-79.

**Sell, S. “Stem Cell Origin of Cancer and Differentiation Therapy.” Crit Rev Oncol Hematol 51, no. 1 (Jul 2004): 1-28.

**Gostjeva, E. V., L. Zukerberg, D. Chung, and W. G. Thilly. Nuclear Morphotypes and Metamorphoses in Human Colonic Ontogenesis and Carcinogenesis. (2005) Manuscript submitted.

Cancers as Clonal Expansions Requiring Multiple Genetic Events

Boveri, T. Zur Frage der Entstehung maligner Tumoren. Fischer, Jena, 1914.

———. “The origin of malignant tumors.” Baltimore: Williams Wilkins, 1929.

**Balmain, A. “Cancer Genetics: From Boveri and Mendel to Microarrays.” Nat Rev Cancer 1 (2001): 77-82.

The Genetic Events in Carcinogenesis: Chromosomal Aberrations in Oncogenes and Tumor Suppressor Genes

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.

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.

Anonymous. Mitelman Database of Chromosome Aberrations in Cancer. Edited by F. Mitelman, B. Johansson, F. Mertens. 2002.

Retinoblastoma, Other Familial Early Onset Cancer Syndromes and the “Two Allele Inactivation” Model of Initiation

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.

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.

**Knudson, A. G. “Cancer Genetics.” Am J Med Genet 111, no. 1 (Jul 22, 2002): 96-102.

Weinberg, R. A. “How Cancer Arises.” Sci Am 275, no. 3 (Sep 1996): 62-70.

**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.

Origins of Onco-mutations in Humans

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.

**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.

**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.

**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.

**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.

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.

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)

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.

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.

Thilly, W. G. “Have Environmental Mutagens Caused Onco Mutations in People?” Nature Genetics 34 (2003): 255-259.

Background Literature in Mutational Spectrometry: History and Technology

**Benzer, S. “The Fine Structure of the Gene.” Sci Am 206 (Jan 1962): 70-84.

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.

Benzer, S. “Genetic Fine Structure.” Harvey Lect 56 (1960-1961): 1-21.

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.

Benzer, S. “Genetic Fine Structure and its Relation to the DNA Molecule.” Brookhaven Symp Biol 8 (Feb 1956): 3-5.

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.

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.

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.

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.

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.

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.

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.

**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.

Luria, S. E. “Mutation of Bacterial Viruses Affecting their Host Range.” Genetics 30 (1945): 84-99.

Leung, E. S. “A Modified Method for the 1000-compartment Fluctuation Test.” Heredity 33, no. 3 (Dec 1974): 417-9.

Course Info
As Taught In
Spring 2005