Cancer: A global concern

The epidemiology of CancerFarid Najafi

School of Population HealthKermanshah 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

A B

cancer

other causes

exposure

Onset of disease

Diagnosis TreatmentFollow-up

Pre-clinical phase Clinical phase

Survival

Incidence Mortality

The disease process

C

Events

Cancer burden indicators

Prevalence

Death

• 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: Mortality

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 population-based 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 liver• Human papilloma cervix, vulva, vagina,

penis, anus

• EBV Burkitt’s lymphoma, Hodgkin’s lymphoma, naso-pharyngeal ca

• Human herpes (8) Kaposi’s sarcoma• various T-cell leukaemia,

mesothelioma..

diet and cancer

aflatoxin liver cancer

‘salted fish” NPC(salted foods stomach cancer)

overeating/ gall bladder, uterus, obesity breast (post-menopause)

vegetables/ lung, stomach,

fruit 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 deathsIran (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 EUROCARE-4 STOMACHSTOMACHAge standardized 5-year relative survival, by country (both sexes)Age standardized 5-year relative survival, by country (both sexes)

Sant et al EJC, 2009

0 20 40 60 80 100

EUROCARE-4 POOL

Poland

Czech Republic

Spain

Slovenia

Portugal

Malta

Italy

Switzerland

Netherlands

Germany

France

Belgium

Austria

UK Wales

UK Scotland

UK Northern Ireland

UK England

Ireland

Sweden

Norway

Iceland

Finland

Denmark

5-year relative survival (%)0 20 40 60 80 100

EUROCARE-4 POOL

Poland

Czech Republic

Spain

Slovenia

Portugal

Malta

Italy

Switzerland

Netherlands

Germany

France

Belgium

Austria

UK Wales

UK Scotland

UK Northern Ireland

UK England

Ireland

Sweden

Norway

Iceland

Finland

Denmark

5-year relative survival (%)

Colon and Rectum Stomach

Incidence ASRx100,000Incidence ASRx100,000Tehran M 20Tehran M 20Tehran F 10Tehran F 10Europe M Europe M W <5W <5 E 30E 30 N <5N <5 S 18S 18

5-year survival 25%5-year survival 25%Range= 14-32%Range= 14-32%

Northern EuropeUK and IrelandCentral EuropeSouthern EuropeEastern Europe

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 EUROCARE-4 LUNG CANCERAge-standardized 5-year relative survival by Age-standardized 5-year relative survival by countrycountry

Sant et al. EJC 20090 20 40 60 80 100

EUROCARE-4 POOL

Poland

Czech Republic

Spain

Slovenia

Portugal

Malta

Italy

Switzerland

Netherlands

Germany

France

Belgium

Austria

UK Wales

UK Scotland

UK Northern Ireland

UK England

Ireland

Sweden

Norway

Iceland

Finland

Denmark

5-year relative survival (%)

Incidence ASRx100,000Incidence ASRx100,000Tehran M 15Tehran M 15Tehran F 7Tehran F 7Europe MEurope M between 42-65between 42-65

5-year survival 12%5-year survival 12%Range = 8-15%Range = 8-15%

Northern EuropeUK and IrelandCentral EuropeSouthern EuropeEastern Europe

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

Minami, H. et al. Chest 2000;118:1603-1609

Actual survival curves of 647 patients >= 60

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