CANCER EPIDEMIOLOGY AND PATHOGENESIS (EPID 770)
SPRING 2016
Tues/Thurs 9:30‐10:45 Instructor: Melissa Troester, Ph.D., M.P.H. Office: 2104H McGavran Greenberg Email: [email protected]
COURSE OBJECTIVE
The objective of this course is to provide a framework for understanding and critically evaluating etiologic literature. The course will cover cancer statistics, major risk factors for cancer, mechanisms of carcinogenesis, biomarkers in cancer research, as well as some current controversies in cancer etiologic research. Students will gain background knowledge of cancer biology and epidemiology needed to interpret and critique cancer prevention research and will develop and practice skills in critiquing literature and identifying knowledge gaps.
RECOMMENDED TEXTBOOKS
There is no assigned textbook for the course, but these texts may be useful as references:
Nasca and Pastides. Fundamentals of Cancer Epidemiology (2nd Ed). Jones and Bartlett, Sudbury, MA 2008.
Schottenfeld and Fraumeni. Cancer Epidemiology and Prevention, (2nd or 3rd Ed). Oxford, New York, NY 1996, 2006.
ASSIGNED READINGS
Assigned readings and study questions will be provided for each class through Sakai.
COURSE REQUIREMENTS
Class participation (10%)
Literature Critique (2 X 20%)
Homework Assignment (4 X 5%)
Final Project (30%)
CLASS PARTICIPATION
Each class period will include a discussion of assigned readings and study questions. Students are required to complete reading and/or homework assignments prior to class.
For some lectures, a multiple choice assessment will be provided to students at the start of class. Students should review their responses after class. These self‐assessments are designed to help you evaluate your progress.
Completion of the self‐assessments and class participation (general preparedness and evidence that readings have been completed) will be used as the basis for the class participation grade.
LITERATURE CRITIQUE
Two peer‐review critiques will be written during the semester on assigned articles. The articles will be taken from the current literature and the written critique should resemble a critique that would be written as a reviewer for a scientific journal. The review should begin with a summary of the purpose/scientific objective of the article and proceed to discuss strengths as well as areas for improvement. It is often helpful to divide the review into major and minor criticisms. Where appropriate, page, paragraph, and line numbers should be indicated for each major and minor point made in the critique. Students wishing to receive feedback on their first critique may submit the critique two weeks prior to the due date.
HOMEWORK
Three homework assignments will be assigned. The homework will be graded as P/F, but will be required to be turned in during class. In class discussion of the homework will be used to help students assess their work and discussion will contribute to the class participation grade.
FINAL PAPER
A final project will be presented in the final days of class. This project will require a careful and critical literature review related to a specific research question and hypothesis in cancer epidemiology, integrating biologic and epidemiologic literature to identify gaps and conflicts. Students should submit a one page summary of their intended project topic by March 3.
COURSE SCHEDULE
CANCER STATISTICS AND SURVEILLANCE
1 Jan 12 Cancer Statistics: Overview
2 Jan 14 Cancer Statistics: Incidence
3 Jan 19 Cancer Screening (Nichols)
4 Jan 21 Cancer Statistics: Mortality & Survival
THEORIES AND BIOLOGY OF CARCINOGENESIS
5 Jan 26 Multi‐stage Models
6 Jan 28 Theories of Carcinogenesis
Homework 1 due
7 Feb 2 Classification of cancers
8 Feb 4 Histopathology 1
9 Feb 9 Histopathology 2 (Sherman by WebEx)
10 Feb 11 Induction and Latency
Literature Critique 1 due
CANCER SITES AND ETIOLOGIC FACTORS
11 Feb 16 Genetics
12 Feb 18 Family history
Homework 2 due
13 Feb 23 Infectious Diseases/HPV & Cervical Cancers (Smith)
14 Feb 25 Obesity (Allott)
15 Mar 1 Hormones & Endometrial Cancer (Sherman)
16 Mar 3 Ovarian Cancer (Sherman)
17 Mar 8 Alcohol & Smoking
18 Mar 10 Aging
19 Mar 22 Pharmacoepidemiology and Cancer Etiology (Lund)
BIOMARKERS IN CANCER EPIDEMIOLOGY
20 Mar 24 Observation vs. Experimentation:
Dietary Studies with Surrogate Endpoint Biomarkers
Homework 3 due
21 Mar 29 Observation vs. Experimentation – In Class Exercise
22 Mar 31 Chemoprevention (Baron)
23 Apr 5 Biomarkers: Overview, Design and Biases
Literature Critique 2 due
24 Apr 7 Biomarkers: Paper discussion
CONFLICTING STUDIES IN CANCER EPIDEMIOLOGY
25 Apr 12 Resolving conflicting studies – Small Groups
26 Apr 14 Resolving conflicting studies – Class debate
Assignment 4 due
27 Apr 19 Final Projects
28 Apr 21 Final Projects
29 Apr 26 Final Projects
READING LIST
CANCER STATISTICS
Overview
Bailar JC and Gornik HL. (1997) Cancer Undefeated. New England Journal of Medicine, 336: 1569 – 1574.
Jemal et al. (2015) Annual Report to the Nation on the Status of Cancer, 1975‐2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State. J Natl Cancer Inst, 107: djv048.
Incidence
Smith BD et al. (2009) Future of Cancer Incidence in the United States: Burdens Upon an Aging Changing Nation. J Clin Oncol. 27: 2758‐2765.
Clegg LX et al. (2002) Impact of Reporting Delay and Reporting Error on Cancer Incidence Rates and Trends. Journal of the National Cancer Institute. 94: 1537‐45.
Screening
Newcomb et al. (2012) Impact of colon cancer screening on family history phenotype. Epidemiology 23: 308–310
Weiss NS (2003) Adjusting for Screening History in Epidemiologic Studies of Cancer: Why, When and How to Do it. Am J Epidemiology 157: 957‐961.
Mortality & Survival
Albano et al. (2007) Cancer Mortality in the United States by Education Level and Race. Journal of the National Cancer Institute, 99: 1384‐1394.
Wingo et al. (1998) Long‐Term Cancer Patient Survival in the United States. Cancer Epidemiology, Biomarkers & Prevention. 7: 271‐282.
Janssen‐Heijnen et al. (2007) Prognosis for long‐term survivors of cancer. Annals Oncology 18: 1408‐1413.
THEORIES AND BIOLOGY OF CARCINOGENESIS
Multi‐stage Model
Kaldor H, Day N. “Mathematical models in cancer epidemiology.” in: D Schottenfeld, J Fraumeni. Cancer Epidemiology and Prevention, Second Edition (Philadelphia, 1996). pp. 127‐ 137
Day N, Brown C. Multistage models and Primary Prevention of Cancer. J Natl Cancer Inst 64: 977‐89 (1980).
Harding C et al. Cancer suppression at old age. Cancer Res 68: 4465‐78 (2008).
Hallmarks of Cancer/Theories of Carcinogenesis
REQUIRED Hanahan and Weinberg (2000) The hallmarks of cancer. Cell 100:57‐70.
REQUIRED Vineis P, Schatzkin A, and Potter JD. (2010) Models of carcinogenesis: An overview. Carcinogenesis 31:1703‐1709
OPTIONAL Merlo LMF, Pepper JW, Reid BJ, Maley CC. (2006) Cancer as an evolutionary and ecological process. Nature Reviews Cancer 6: 924‐935.
OPTIONAL Michor F, Miwasa Y, and Nowak MA. (2004) Dynamics of Cancer Progression. Nature Reviews Cancer 4:197‐205.
OPTIONAL Potter JD. (2007) Morphogens, morphostats, microarchitecture and malignancy. Nature Reviews Cancer 7:464‐474
OPTIONAL Gatenby RA and Gillies RJ. (2008) A microenvironmental model of carcinogenesis. Nature Reviews Cancer 8:56‐61
Induction and Latency
Rothman K. (1981) Induction and latent periods. Am J Epidemiol 114: 253‐259.
Giovannucci E. (2001) An updated review of the epidemiological evidence that cigarette smoking increases risk of colorectal cancer. Cancer Epidemiol Biomark Prev 10: 725‐731.
Histopathology
Sherman et al. (2010) Molecular pathology in epidemiologic studies: A primer on key considerations. Cancer Epidemiology Biomarkers Prevention; 19:966‐972
http://www.cancer.gov/cancertopics/factsheet/detection/staging
http://www.cancer.gov/cancertopics/factsheet/detection/tumor‐grade
CANCER ETIOLOGIC FACTORS
Aging
TBD
Genetics
Schroeder JC et al. (2003) p53 mutations in bladder cancer: evidence for exogenous versus endogenous risk factors. Cancer Research 63: 7530‐7538.
Family History
REQUIRED Murff et al. (2002) Does this patient have a family history of cancer? JAMA 292(12): 1480‐1489.
REQUIRED Ponder BAJ. (2001) Cancer genetics. Nature 411:336‐341.
OPTIONAL Khoury and Flanders (1995) Bias in using family history as a risk factor in case‐control studies of disease. 6:511‐519.
OPTIONAL Murta‐Nascimento et al. (2007) Risk of bladder cancer associated with family history of cancer: do low‐penetrance polymorphisms account for increase in risk. 16:1595 – 1600.
Obesity
Calle EE and Kaaks (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nature Reviews Cancer (4):570‐591.
Alcohol
Sitz HK and Stickel F. (2007) Molecular mechanisms of alcohol‐mediated carcinogenesis. Nature Reviews Cancer 7:599‐612.
Allen NE, Beral V, Casabonne D et al. (2009) Moderate alcohol intake and cancer incidence in women. J Natl Cancer Institute, 101: 296‐305.
Bagnardi V, Randi G, Lubin J et al. (2010) Alcohol consumption and lung cancer risk in the environment and genetics in lung cancer etiology (EAGLE) study. Am J Epidemiol 171:36‐44.
BIOMARKERS IN CANCER EPIDEMIOLOGY
Biomarkers (Overview)
Schatzkin A and Gail M. (2002) The promise and peril of surrogate end points in cancer research. Nature Reviews Cancer. 2:1‐9.
Vineis and Perera (2007) Molecular epidemiology and biomarkers in etiologic cancer research: the new in light of the old. Cancer Epidemiol Biomarkers Prev 16: 1954‐1965.
Biomarkers: Design and Biases
Ransohoff DF. (2005) Bias as a threat to the validity of cancer molecular‐marker research. Nature Reviews Cancer 5: 142‐145.
Ransohoff DF. (2004) Rules of evidence for cancer molecular‐marker discovery and validation. Nature Reviews Cancer 4: 309‐314.
Biomarker Paper Discussion
Aleksandrova K, Jenab M, BOehing H et al. (2010) Circulating C‐reactive protein concentrations and risks of colon and rectal cancer: a nested case‐control study within the European Prospective Investigation into Cancer and Nutrition. Am J Epidemiol 172:407‐18.
Observation vs. Experimentation
Martinez ME, Marshall JR, Giovannucci E. (2008) Diet and cancer prevention: the roles of observation and experimentation. Nature reviews cancer. 8: 694‐703.
Rohan TE, Negassa A, Caan B et al. (2008) Low‐fat dietary pattern and risk of benign proliferative breast disease: a randomized, controlled dietary modification trial. Cancer Prev Res. 1:275‐84.
von Elm E, Altman DG, Egger M, et al. (2007) The strengthening and reporting of observational studies in epidemiology (STROBE) statement: Guidelines for reporting observational studies. Plos Medicine 4:e296.