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Cancer: A global concern The epidemiology of Cancer Farid Najafi School of Population Health Kermanshah University of Medical Sciences (KUMS) 2008 What is cancer? • • • A generic term for a group of more than 100 diseases ‘Malignant tumours’ and ‘Neoplasm’ are other names Charecterized by followings: – Rapid creation – Metastasis Oncogenesis: The process whereby normal cells become cancer cells cancer... • unrestrained cell division + • disordered tissue growth • local invasion • distant spread cancer... • failure to control growth • genetic imbalance: • excess stimulus (oncogene activation) • loss of tumour suppression • act via various factors (eg loss of telomerase, angiogenesis) DNA errors: may be inherited; or acquired Functional properties of tumor cells 1. Contact inhibition of cell movement 2. Immortality of cells Primary vs. Secondary tumors • The original tumor is called a primary tumor and all cells derive from single aberrant cell • As tumors metastasize the new colonies or foci are refferred to as secondary tumors or metastatic centers Malignant transformation • Initiation: a change in the cell’s genetic material primes the cell to become cancerous. Change may be spontanous or by an agent that cause cancer (carciongen) • Promotion: Unlike carcinogens, promoters do not cause cancer by themselves. They allow a cell that has undergone initiation to become cancerous • Spread: Biology of cancer 1. Healthy cells 2. Dysplasia: subtle morphological abnormalities 3. Carcinoma in Situ: abnormality in proliferation but no invasion into the underlying basement membrane 4. Localize cancer (I): invasion to the local tissues 5. Regional spread (II & III): invasion to the regional or extended regional lymph nodes 6. Generalized disease (IV): blood-borne metastasis Cancer burden indicators • Cancer control policies are based on the availability of statistical measures of the impact of cancer in a population • Main epidemiological indicators are cancer mortality, incidence, prevalence, and survival • These four indicators describe different aspects of the disease impact and of the efficacy of health care system in controlling the disease • They are related each other and overall they are a complete set of indicators to describe cancer burden The disease process Events Pre-clinical phase Onset of disease Clinical phase Diagnosis Treatment Follow-up Death cancer exposure A B C other causes Survival Prevalence Incidence Mortality Cancer burden indicators Cancer burden indicators: Mortality • Mortality - Number of cause-specific deaths occurring in a defined population in the unit of time. Usually expressed as rate per 100,000 persons/year • Classification: ICD-9 or 10 • Availability: cause specific mortality data from official statistics in almost all countries. Local/regional/national geographical detail. Cancer burden indicators: Incidence • Incidence – Number of new cancer cases diagnosed in a defined population in the unit of time. Usually expressed as rate per 100,000 persons/year. • Classification: ICD-O (3° revision) topography and morphology • Availability: in areas covered by populationbased Cancer Registries (CR). Good quality data. Cancer burden indicators: Survival – Cause of death known Cancer Specific Survival probability of surviving cancer after x years from diagnosis in a cohort of patients diagnosed in a period of time t – Cause of death unknown Relative Survival (RS) ratio of the observed survival in the patients group to the expected survival in a similar group in the population (same age, sex, year, area, socio-economic class etc…) – RS measures the extra-risk of dying of cancer patients by removing the competitive mortality due to causes other than cancer. Cancer burden indicators: Prevalence • Prevalence – The number of surviving cancer patients in a population at a defined index date. – Usually expressed as count or proportion x 100.000 – Total (or complete) prevalence involves all survivors irrespectively of the date of diagnosis. – Partial prevalence by years from diagnosis represents the number of survivors by limited disease duration. Some facts about cancer • A leading cause of death (13% of all deaths in 2005 worldwide) • >70% of cancer deaths in 2005 occurred in developing countries • Common types of cancers: – Men: Lung, stomach, liver, colorectal, oesophagus and prostate – Women: Breast, lung, stomach, colorectal and cervical the cancer burden 2000: 10 million new cases (world) 2020: 20 million new cases -70% in countries with < 5% cancer control resources Some facts about cancer • 40% of cancer can be prevented • Smoking is the single largest preventable cause of cancer in the world • 1/5 of cancers are due to chronic infections: – – – – – HBV: liver cancer HPV: cancer of cervix Helicobacter pylori: stomach cancer Schistosomes: cancer of bladder HIV infection: kaposi sarcoma and lymphomas Cancers in developed and developing countries • Developed countries – Cancer is the second-biggest cause of death after CVD – Prostate, breast and colon cancer are the most common types • Developing countries – Death due to cancer is going to mimic developed countries – Stomach, lung and cervical cancer are more common • World – Lung cancer kills more people than any other cancer Some other facts about cancer The rule of Thirds 1/3 preventable; 1/3 curable (1/2 in developed countries The importance of screening Earlier diagnosis means more curability Cause of cancers 1. Physical agents • • • Ionizing radiation: X-rays & Radioactivity Nonionizing radiation: Sunlight Physical substances: Asbestos & pollution 2. Chemical agents • • Promotion and initiation Industrial exposure • Benzene, benzidine, cadmium, nickel or vinyl choloride Cause of cancers Biological agents • • Viruses Parasites Diet • • • Dietary fat Food preservation Protective substances in the diet Cause of cancers Social factors • Social class • Occupation • Industrial hazard • Medical Services and care • Radiation and medications • Lifestyle • Habits and food hadling • Air and water pollution avoidable cancer causes • smoking (30%) • diet (20-50%) • • • • • infection (10-20%) radiation (6%) alcohol (5%) occupation (3%) pollution (1-5%) • (reproductive hormones 10-20%) Global action against cancer, WHO, 2005 Causes of cancer • Tobacco consumption is the world’s most avoidable cause of cancer • 30% of all cancer deaths in developed countries • The contribution of diet and inactive lifestyle to cancer is similar to smoking in developed countries • One-fifth of cancers worldwide are due to chronic infections smoking and cancer • • • • • • • • mouth pharynx oesophagus larynx lung pancreas kidney bladder lip, nose, stomach. myeloid leukaemia (liver, large bowel, cervix) infection and cancer • parasites: bladder, bowel, liver, bile ducts (Asia, Africa) • bacteria: stomach (? bladder, bowel) • viruses: numerous viruses and cancer • Hepatitis B,C • Human papilloma • EBV • Human herpes (8) • various liver cervix, vulva, vagina, penis, anus Burkitt’s lymphoma, Hodgkin’s lymphoma, naso-pharyngeal ca Kaposi’s sarcoma T-cell leukaemia, mesothelioma.. diet and cancer aflatoxin ‘salted fish” liver cancer NPC (salted foods stomach cancer) overeating/ obesity vegetables/ fruit gall bladder, uterus, breast (post-menopause) lung, stomach, oesophagus, mouth, pharynx, colon, breast, pancreas, bladder treatment strategies (i) screening: breast large bowel cervix prostate lung treatment strategies (ii) • cures (chemoRx, hormone Rx, XRx) • extend life (as above + lifestyle change) • palliate always The role of epidemiological knowledge in disease control: a case of two cancers Intervntion Accepted utility for widescale use Lung cancer Breast cancer Prevention YES. Smoking cigarettes is the strong risk factor; and exposure is modifiable by actions at personal and community levels NO. Many weak risk factors, most not readily modifiable Screening NO. Even the newest tests (CT lung scans) yield very limited survival benefits YES. Substantial good evidence (RCTs) of lower mortality due to population screening programs for over 50s Improved treatment NO. Minor survival improvements only with newer treatments YES. RCT results show survival advantage with appropriate chemotherapy/radiotherapy Cancer in Iran Causes of deaths Iran (2005, 2030) WHO, 2007 Some facts about cancer in Iran • In 2005 cancer killed 47,000 people in Iran, 27,000 of those people were under the age of 70 • In 2002 stomach cancer was the most common cancer found in men in Iran • In 2005 stomach cancer was the leading cause of cancer deaths in women and men Incidence of cancer (Iran, 2002) Cancer deaths (Iran, 2005) Incidence of cancer (Iran, United States) Incidence of cancer (Iran, United State) Gastric Cancer Biology • Several Hystological types of gastric cancer of which adenocarcinoma is by the most frequent • Sarcomas and lymphomas are other types • This lecture mainly focous on adenocarcinoma Epidemiology • Infrequent before 40 years of age • Twice as frequent in men than in women • Leading cause of death from cancer worldwide and in Iran • Highest incidence in Japan, South America and Eastern Europe • Adjusted rate worldwide is 15.62% per 100,000 EUROCARE-4 STOMACH Age standardized 5-year relative survival, by country (both sexes) Colon and Rectum Stomach Incidence ASRx100,000 Tehran M 20 Tehran F 10 Europe M W <5 E 30 N <5 S 18 Denmark Denmark Finland Finland Iceland Iceland Norway Norway Sweden Sweden Ireland Ireland UK England UK England UK Northern Ireland UK Northern Ireland UK Scotland UK Scotland UK Wales UK Wales Austria Austria Belgium Belgium France France Germany Germany Netherlands Netherlands Switzerland Switzerland 5-year survival 25% Range= 14-32% Italy Italy Malta Malta Portugal Portugal Slovenia Slovenia Spain Spain Czech Republic Czech Republic Poland Poland EUROCARE-4 POOL EUROCARE-4 POOL 0 20 40 60 80 5-year relative survival (%) 100 Northern Europe UK and Ireland Central Europe Southern Europe Eastern Europe 0 20 40 60 80 100 5-year relative survival (%) Sant et al EJC, 2009 Risk factor of gastric cancer • Chronic Atrophic Gasteritis is the first step in the development of most gastric cancer, associated with: – Tobacco – H.pylori infection – Diet with high level of nitrites, nitrates, salt and smoked food – Previous gastric surgery – Pernicious anemia (B12 deficiency due to absence of interinsic factor+atrophic gastritis tobacco • Increases the risk of gastric cancer by 50% • Responsible for 11% of all Stomach Cancer • Decreases the level of carotenoids and Vitamin c • Increases the risk of H.pylori Helycobacter pylori • Associated with a two to sixfold increase in the risk of developing Gastric Cancer • In 1994 the WHO designated H.pylori a group 1 carcinogen Dietary factors • Consumption of fruit, vegetables and fiber have a protective effect against Gastric Cancer • Their effect is probably associated with Vitamin C or carotenes • Nitrates and nitrites are usually found in salted, smoked and dried foods Genetic factors • Blood type A • A first degree relative with Gastric Cancer • Hereditary non-polyposis colorectal cancer Secondary prevention • Early detection: difficult due to lack of symptoms • Screening might be effective where the disease is a major health problem (such as Japan) – Gas-contrast Stomach Fluorography – Further paraclinical tests (endoscopy and biopsy) if the result is abnormal Conclusion • High mortality rate • The best primary prevention strategies are: – Smoking cessation – Healthy diet – Avoidence of salted, smoked and poorly preserved foods – Erradication of H.pylori Lung cancer Some facts about lung cancer • Lung cancer is the third most common cancer in the western world, after prostate and breast cancer • One of the most preventable kinds of cancer • Four out of five cases are associated with smoking EUROCARE-4 LUNG CANCER Age-standardized 5-year relative survival by country Incidence ASRx100,000 Tehran M 15 Tehran F 7 Europe M between 42-65 Denmark Finland Iceland Norway Sweden Ireland UK England UK Northern Ireland UK Scotland UK Wales Austria Belgium 5-year survival 12% Range = 8-15% France Germany Netherlands Switzerland Italy Malta Portugal Slovenia Spain Czech Republic Poland EUROCARE-4 POOL 0 20 40 60 80 5-year relative survivalSant (%) Northern Europe UK and Ireland Central Europe Southern Europe 100 Eastern Europe et al. EJC 2009 Risk factors • Tobacco and passive smoking – Smokers have a 10-25 times higher risk compared to non-smokers – 10%-20% of all lung cancers in non smokers are due to passive smoking • Air pollution – Exposure to air pollution increase the risk of lung cancer by 100% • Chronic obstructive lung disease (COPD) • Occupational exposure – Asbestos, glass-wool and ceramic fibres • Genetic factors Taylor R et al 2007 Prevention of lung cancer • 80%-85% of lung cancers are associated with smoking • 10% are associated with occupational carcinogens • 1% are associated with passive smoking Histological types of lung cancer • Two major types: – Small-cell lung cancer – Nonsmall-cell lung cancer • Squamous cell carcinoma • Adenocarcinoma • Large-cell carcinoma • Squamous cell carcinoma is the most commonest type in males and adenocarcinoma is the most commonest type in females Early detection of lung cancer • Low cure rate (13%) • Low cure rate is related to lack of early detection measures • There is no successful screening test Actual survival curves of 647 patients >= 60 Minami, H. et al. Chest 2000;118:1603-1609 Conclusion • NO currently established means for the screening or early detection of lung cancer • 85-88% of all lung cancer are caused by active or passive smoking • Reduction of tobacco consumption still is the most important strategy