3. สม ฏฐานว ทยาของมะเร ง (Cancer Etiology)

Transcription

1 ว ตถ ประสงค 3. สม ฏฐานว ทยาของมะเร ง (Cancer Etiology) สม ฏฐานว ทยา : การศ กษาเก ยวก บสาเหต ของการเก ดโรค สามารถอธ บายว ธ การศ กษา ว ธ การศ กษาสาเหต ของการเก ดมะเร งได สามารถอธ บายสาเหต สาเหต ของการเก ดมะเร งได Content 1. The approaches for identifying the causes of cancer 2. The main causes of human cancer

2 1. The approaches for identifying the causes of cancer :Epidemiological and Experimental approaches 1.1 The Epidemiological approach - Epidemiology = the branch of medical science that investigates the frequency and distribution of diseases in human populations - Epidemiologists study the patterns of disease distribution in human populations. - The goal of epidemiology is to establish causal factors for health issues in order to improve the health and safety of whole populations. - Incidence of cancers in different populations provides clues as to the causes of specific cancers. - The larger the sample, the more likely it is that the true value will be revealed (p value of 0.05 or less is required for a statistically significant difference). - Epidemiology : -Descriptive, -Analytical, and -Molecular Descriptive epidemiology - focuses on identifying and reporting both the pattern and frequency of health events in a population. -Data concerning person, place & time are necessary for describing the patterns of health and disease in human populations.

3 - Person characteristics include sociodemographic characteristics such as age, race/ethnicity, education,income, insurance status, occupation, parity, and marital status as well as behaviors such as substance abuse, diet, sexual activity or use of health care services. - Place characteristics include geographic location (e.g., urban versus rural), features of the geography (e.g., mountainous region, area with wells as the major water source), population density, as well geo-political boundaries (e.g., census tracts, cities, counties, or states), and location of worksites, schools, and health facilities. - Time characteristics include cyclical changes, long term secular trends, and even daily or hourly occurrences during an epidemic. -uses data from large populations of people ---> general conclusions -the data can be useful for more specific analyses -the data do not tell what exactly cause cancer -TheIncidence and Mortality rates can be calculated as: [Number of people either developing (incidence) or dying (mortality) from a specific cancer in a specific time period /total population at that time] - Population numbers are usually corrected per 100,000 people. - The ages of population are also corrected. - Descriptive studies are useful for defining biological hypotheses that can be tested by other means.

4 Examples: Descriptive epidemiological data Male cancer deaths (USA), age corrected The 5-year survival rates for selected cancer (USA) at different time periods. King RJB,Cancer Biology. 1996

5 1.1.2 Analytical epidemiology - focuses on the search for the determinants of health outcomes. - Analytical epidemiologists use data gathered by descriptive epidemiology experts to look for patterns suggesting causation. - compare two or more groups of people with different characteristics. - false conclusion may be due to: 1) selection bias inappropriate selection of people for comparison 2) recall bias inadequate measures of exposure - two approaches: (1) case-control comparison (2) cohort comparison Case-Control Comparison: - Compare the characteristics of cases; -- cancer patients with specific characteristics -- healthy individuals with specific characteristics -- controls who do not have cancer or the characteristic in question - compare the frequency with which an exposure occurred in the cases versus the controls ---- > to identify risk factors of specific cancer

6 - Advantage; Providing quick answers - Major concerns; what are the appropriate controls and fidelity of recall of past events Case-Control analysis of cervical cancer in Colombia King RJB,Cancer Biology. 1996

7 Cohort Comparison - Start with a well-defined, healthy population (a cohort), and compare those who get cancer in the ensuing years with those who do not. - Provide more reliable data but at the cost of increased complexity and expense Prospective cohort analysis of relative risks of developing leukemia in people of the stated ages at the time of exposure to atomic radiation in Hiroshima/Nagasaki. King RJB,Cancer Biology. 1996

8 1.1.3 Molecular epidemiology - combines epidemiological methods with molecular analysis to help determine carcinogenic events - mutation types of specific genes may point to causative agents Types of p53 mutations in Liver cancers in four regions of East Asia Hepatitis B virus infection = risk factor Qidong province in China ---> aflatoxin King RJB,Cancer Biology. 1996

9 1.2 The Experimental approach Randomized trial (assigning people to receive varying doses of a suspected agent) Cannot perform active experiment in human ---> unethical Animal testing is an alternative way. Animal testing and epidemiology are complementary approaches. Epidemiological data Animal testing data Animal testing Epidemiological approach Animal testing is useful for the preliminary identification of possible human carcinogens Carcinogens = cancer-causing agents By law, any new chemical introduced for human consumption in the US must be first tested in animals (rats or mice) to check for possible carcinogenic effects.

10 In general, a high level of agreement has been detected between the ability of substances to cause cancer in humans and in animals. Some examples of proven human carcinogens that also cause cancer in animals. Nonetheless, there is no guarantee that a substance found to cause cancer in animals will always do so in humans. Kleinsmith LJ. Principles of cancer biology

11 The Ames test permits rapid screening for chemical carcinogens that are mutagens. Cancer-causing agents often act as mutagens. Ames Test by Bruce Ames, 1950s MMS=Methylmethanesulfonate MOCA=4-4 -methylenebis(2-chloroaniline) Kleinsmith LJ. Principles of cancer biology A strong correlation between a chemical s ability to cause mutations and its ability to cause cancer.

12 2. The main causes of human cancer 2.1 Cancer rates increase dramatically with age The risk factor with the greatest influence in determining whether a person will develop cancer is age. Relationship between age and cancer risk. The risk of developing cancer after age of 60 is much greater than for people under age 40. Kleinsmith LJ. Principles of cancer biology

13 2.2 Environmental and lifestyle factors play a prominent role in triggering the development of cancer The particular kinds of cancer arise with differing frequencies in different part of the world. The likelihood of developing a particular kind of cancer for a person of a given age, say 50 years old, is significantly affected by the country in which that person lives. The causes of cancer are to be found in factors that differ between country rather than in the process of aging. - Environmental factors ---> % - Genetic makeup (Hereditary factors) ---> % Environmental factors -Physical Environment - Social and cultural Environment

14 Geographical differences in the prevalence of different kinds of cancer. Kleinsmith LJ. Principles of cancer biology

15 Comparison of stomach and colon cancer rates in Japan, in the US, and in Japanese immigrants to the US. The environmental factors are more important than heredity in causing cancer. Kleinsmith LJ. Principles of cancer biology

16 2.3 Tobacco smoke is responsible for approximately one-third of all cancer deaths Lung cancer rates in the US began to increase about 25 years after the increase in smoking rates. Many studies have made it abundantly clear that smoking is the underlying cause of most lung cancers. Relationship between cigarette smoking and lung cancer in the US. Death rates for breast cancer and lung cancer in woman Kleinsmith LJ. Principles of cancer biology

17 A dose-response relationship exists between exposure to tobacco smoke and the risk of developing cancer Kleinsmith LJ. Principles of cancer biology Lung cancer rates are directly proportional to the number of cigarettes smoked per day. Long-term smokers develop lung cancer more frequently than do shortterm smokers. Smokers who inhale deeply develop lung cancer more frequently than smokers who do not inhale deeply.

18 Tobacco smoke contains more than 4000 different chemicals, more than 40 of which are carcinogenic when administered to animals. Kleinsmith LJ. Principles of cancer biology

19 2.4 Alcohol acts synergistically with tobacco to increase cancer risk Cancer of the mouth and throat (Oropharyngeal cancer) increases significantly in people who drink, smoke, or both. Kleinsmith LJ. Principles of cancer biology Alcohol and tobacco are a deadly combination because tobacco smoke contains potent carcinogens that create DNA mutations and alcohol then stimulates the proliferation of the genetically damaged cells.

20 2.5 Food contains carcinogens as well as anticarcinogens Food is a complex mixture of thousands of different chemicals. Examples of some natural chemicals in fruits and vegetables that are carcinogenic when tested in animals Kleinsmith LJ. Principles of cancer biology Examples of some possible anticarcinogens: Lycopene (tomatoes), epigallocatechin gallate (green tea), resveratrol (skin of red grapes), sulfides (garlic)

21 Red meat, saturated fat, excess calories and obesity may all contribute to cancer risk High-fat diets are known to cause the liver to secrete large amounts of bile acids into the intestines. Lithocholic acid can produce DNA damage and has been found to induce colon cancer when injected into animals. Colon cancer rates are seen to increase in direct relation to the amount of meat consumed in each country.

22 Diet appears to be an important factor in determining cancer risk but is difficult to study Human diet consists of a complex mixture of foods that are difficult to study in a systematic way. 2.6 Several types of Radiation cause cancer Radiation = Energy traveling through space Natural sources: UV radiation from the sun -----> skin cancer Cosmic rays from outer space Emissions from naturally occurring radioactive elements Artificial sources: X-rays Radioactivity UV radiation and Ionizing radiation are two main classes clearly identified as causes of cancer. Ionizing radiation : X-rays Nuclear radiation (emitted by radioactive elements)

23 2.7 Viruses and other infectious agents can cause cancer Peyton Rous (1911) discovered Rous Sarcoma Virus : the first demonstration of existence of an oncogenic virus. (Nobel Prizes in Medicine, 1966) Oncogenic viruses: Epstein-Barr virus ---Burkitt s lymphoma Human papillomaviruses ---Cervical cancer Hepatitis B & Hepatitis C viruses ---Liver cancer > cause ~10 % of all cancers worldwide Summary: The main causes of cancer involve chemicals, radiation, infectious agents, and heredity.