Epidemiology of Cancer (Environmental Biology of Cancer) Folder Title: Epidemio(NoTP) Updated: February 2, 2015

Epidemiology of Diseases Distribution of patterns of health and disease. Determination of potential causation that leads to the observed distribution. Observational vs Experimental Sciences: Observe episodes of disease appearance (e.g. geographic "hot- spots" or occupational or familial patterns) Retrospective analysis of potential causative associations Prospective trials to determine causative sources Determine "Relative Risk" or "Odds Ratio" Small vs large Relative Risk Values Association or Correlation is not Causation

Complications in Epidemiological Observations Reliable reproducible data and conclusions vs. firmly held beliefs or "common sense" assumptions. Problems with acquisition of data and data reliability: Time patterns of exposure vs appearance of disease Combinations of causative sources and sequences of exposures High background appearance (non-rare diseases) Usually small impact of an agent on an individual or population Retrospective data: recall bias and data reporting Prospective trials: Costs, ethical problems, subject cooperation Deducing Actual Causation from Epidemiological Data

Epidemiological data comparing high and low incidence rates based on different population groups poses the questions: 1.Why is one group presenting high risk for a given type of cancer? 2.Why is another group presenting relatively low risk for that type of cancer? 3.What does that tell us about causation? 4.Does that present possibilities for prevention and diagnosis?

Breast Cancer Relative Risks

Epidemiological data comparing high and low incidence rates based for different types of cancer based on different countries poses the questions: 1.Why is a given cancer (e.g. liver cancer) high in one set of countries? 2.Why is that same cancer very low in other countries? 3.What does that tell us about causation? 4.Does that present possibilities for prevention and diagnosis? To here January 27th

Table 2.5 part 1 of 2 The Biology of Cancer (© Garland Science 2007) p. 44

Table 2.5 part 1 of 2 The Biology of Cancer (© Garland Science 2007) p. 44 Solar exposure & skin pigmentation ? Epstein-Barr Virus Association ? Hepatitis B Virus Papilloma viruses Helicobacter pylori infection Smoking ? ?

Specific Cancer Incidence and Migratory Patterns: Cancers and Environmental Effects

Figure 2.20 The Biology of Cancer (© Garland Science 2007) Cancer Incidence Following Migration p. 45

Epidemiological Data can also sometimes provide clues about the biological mechanisms underlying certain types of cancers. Malignant Melanoma (Solar radiation exposure) Burkitt’s Lymphoma (Co-infection with virus transmitted by mosquitos also transmitting malaria)

Lifetime Melanoma Risk: 1935 to 1996 Figure 7-8, Biological Basis of Cancer, 1998, p 194 MelRisk

White Males White Females Black Males & Females MelRace

Cancer Incidence and Changes in Gene Expression: Reciprocal Translocation 9 to 22 Reciprocal Translocation: Chronic Myelogenous Leukemia (CML) 8 to 14 Reciprocal Translocation: Burkitts Lymphoma

Figure 1.11b The Biology of Cancer (© Garland Science 2007) Fluorescent in situ hybridization (FISH) of normal metaphase human chromosomes using chromosome specific DNA probes with different fluorescent dyes

Figure 2.23b The Biology of Cancer (© Garland Science 2007) Chromosome-specific Probe Analysis of Reciprocal Translocation (9 to 22) in Chronic Myelogenous Leukemia Chromosome 9 (White); Chromosome 22 (Purple)

Reciprocal translocation between chromosomes 9 and 22 produces fusion of a cancer-inducing gene, the abelson or abl gene with information on another chromosome. This chromosome fusion is expressed as a fusion protein involving the abl gene product. This miss-expressed fusion protein drives cell division in leucocytes leading to chronic myelogenous leukemia. Other types of leukemia are supported by fusions proteins involving the abl gene that are fused at different break points and give fusion proteins of different molecular weights

Figure 4.13a The Biology of Cancer (© Garland Science 2007) p. 109 Reciprocal Translocation (8 to 14) in Burkitt’s Lymphoma

Figure 4.12 The Biology of Cancer (© Garland Science 2007) Incidence of Burkitt’s Lymphoma in Relation to Infectious Disease Etiology: Aedes simpsoni mosquito transmission vector for malaria and Epstein Barr Virus co-infection

Figure 4.13b The Biology of Cancer (© Garland Science 2007 p. 109) Myc Oncogene (Chromosome 8) Expression Controlled by Fusion with Immunoglobulin Heavy Chain Gene (Chromosme 14) in Burkitt’s Lymphoma

Epidemiology of Cancer Based on Age

AgeEffct Incidence

See Figure 11.1, Cancer incidence at various ages for men and women. p Weinberg. Note maximum incidence per 100,000 population at about age 70, then drop off after that age. Serious incidence begins around age 35 except for breast cancer which can have an earlier onset depending on genetics and hormonal status. Why do “super-old” seem to show cancer resistance? Incidence of Various Kinds of Cancers in Men and Women as a Function of Age

The Next Slide is a Turning Point Quiz Question You may not use any notes or electronic devices other than your NXT transmitter. No computers. No phones. No talking or consulting. Make sure that your desk is clear. These are graded quizzes that make up 40% of the overall course grade. They are designed for both you and me to determine whether you are paying attention and following what is going on. You can send a “Response to Leader” while a TP Slide is open. Give it a try. You can communicate with me.

This is from a chronic myelogenous leukemia patient. What is this slide showing? (Short answer question) RankResponses To Here Jan. 30, 2015

Carcinogenic Agents and co-Carcinogenic Agents: Interacting Causations

See also Figure 7-6, Biological Basis of Cancer, p 191

CigDose

Table 2.6 The Biology of Cancer (© Garland Science 2007) p. 46

Figure 11.2 The Biology of Cancer (© Garland Science 2007) Cigarette Consumption and Lung Cancer: 1880 to 2000

I Interacting causative agents: Alcohol and cigarettes

Figure 11.4 The Biology of Cancer (© Garland Science 2007) Squamous cell carcinoma in mice. Mesothelioma in human insulation workers Cancer Incidence and Length of Time of Carcinogen Exposure

Environmental and Occupational Cancers Effects from Nuclear Plant Melt-Down

CxCauses

WorkCx

Table 2.7 The Biology of Cancer (© Garland Science 2007) p. 47

Journal of the National Cancer Institute, July, 1996 Kids&Rad Chernobyl nuclear power- plant melt-down, April 1986

Cultural Associations and Specific Cancers

Journal of the National Cancer Institute October, 1996 StomCxEthnic

Wake up Mom. Time to Play!

Figure 11.3 The Biology of Cancer (© Garland Science 2007) Male Cancer Death Rates for Various Carcinomas, 1939 to Log-Log Plot Slope of 5 indicates a series of rate limiting steps