Epidemiology of Cancer (Environmental Biology of Cancer) Folder Title: Epidemio Updated: January 29, 2013 EpiTitle

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?

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 ? ?

Please respond to this question as a fill-in-the-blank question using the directions provided in the hand-outs. Liver cancer is greatly elevated in Hong Kong and in other places in South East Asia. This is due to 0 of 100

There is elevated risk of breast cancer depending on whether a woman has had a baby or not, and depending on how many babies she has had. What does this suggest as a plausible response to reduce the risk of death from breast cancer? 1.Get pregnant as often as possible. 2.Monitor and control hormonal status. 3.Deny the evidence and don’t worry about it. 4.Eat a low fat diet. 5.Monitor the high risk group more stringently than the lower risk group. 6.Carry out ovariectomy as early in adult life as possible. 0 of 100

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 and gives fusion protein involving the abl gene product that is mis- expressed and drives cell division in leucocytes leading to chronic myelogenous leukemia.

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

Burkitt’s Lymphoma is Associated with co-infection with a virus carried by mosquitos. This is because the virus: 1.Causes point mutations 2.Activates antibody synthesis 3.Turns off a cancer suppressor gene 4.Induces a high fever 5.Secretes a potent chemical carcinogen 0 of 100

What is this slide showing? (Short answer question) 0 of 100

Epidemiology of Cancer Based on Age

AgeEffct

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. Incidence of Various Kinds of Cancers in Men and Women as a Function of Age

Cancer in children and younger adults has an incidence rate of 11% of the total cancers, but accounts for only 5% of the total cancer deaths. Why is that the case? What does that difference between incidence and mortality tell us about cancers in younger persons? (This is a fill-in-the-blank question. Keep it brief. You can use abbreviations if they are clear). 0 of 100

Specific Cancer Incidence and Migratory Patterns: Cancers and Environmental Effects

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

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

(When this slide opens you do not have to send in your name under “Send User Data” unless you borrowed a Response Card from us this morning. If you borrowed a Card be sure to remove the previous name and enter your names. The two previous slides show patterns of cancer incidence within one or two generations in populations of persons who have migrated. What do these data tell us about causation of these cancers? You can abbreviate as long as I reasonably can figure out your meaning. 0 of 100

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

Carcinogenic Agents and co-Carcinogenic Agents: Interacting Causations

CigDose

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

CigBooze

Environmental and Occupational Cancers

CxCauses

WorkCx

Journal of the National Cancer Institute, July, 1996 Kids&Rad

Cultural Associations and Specific Cancers

Journal of the National Cancer Institute October, 1996 StomCxEthnic

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

Detailed analysis of the epidemiology of cancers is important in cancer medicine because it helps us to understand __ ___ ___ ___ ___ ___ (or to) __ __ __ __ __ __ __ some cancers You only need one response 0 of 100

Cancer in children 0 to 14 years of age occurs in 15 per 100,000 as the incidence rate. Cancers in that same group accounts for 2.5 deaths per 100,000. What does that tell us about cancers that affect children ages 0 to 14? (This is a fill-in-the-blank question. Keep it brief. You can use abbreviations if they are clear). 0 of 100

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

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

Understanding the epidemiology of cancers allows us not only to understand the causes of some cancers but also helps us to design programs for the _ _ _ _ _ _ _ _ _ _ of some cancers. One word only! 0 of 100