1. Cancer Epidemiology

2. Epidemiology Leading causes of death in 2001
Percentage of Total Deaths, US
Heart Diseases
Cancer
Cerebrovascular Diseases
Chronic Obstructive Lung Diseases
Accidents
Pneumonia & Influenza
Diabetes Mellitus
Suicide
Nephritis
Cirrhosis of the Liver
Epidemiology: Leading Causes of Death
In one developed country, the United States, for which complete epidemiologic data are available for 2001, cancer is second only to heart disease as the leading cause of death. Cancer deaths account for slightly less than one-quarter of all deaths in the United States, substantially ahead of other common causes of death.
Greenlee RT, et al. CA Cancer J Clin. 2001:51;15-36.

3. Epidemiology Leading cancers worldwide
Total New Rank Males Females Both Sexes Cases
1 Lung Breast Lung 1,037,000
2 Stomach Colon/rectum Stomach 798,000
3 Colon/rectum Cervix uteri Breast 796,000
4 Prostate Stomach Colon/rectum 783,000
5 Liver Lung Liver 437,000
6 Mouth/pharynx Ovary Prostate 396,000
7 Esophagus Corpus uteri Cervix uteri 371,000
8 Bladder Liver Mouth/pharynx 363,000
9 Leukemia Mouth/pharynx Esophagus 316,000
10 NHL* Esophagus Bladder 261,000
Epidemiology: Leading Cancers Worldwide
Worldwide, 8.1 million new cancer cases were estimated for 1990, the most recent year for which complete global data are available. The ranking of the 10 most common sites for new cancers among men and women are shown in this slide. The four most common sites in both sexes combined were lung, stomach, breast, and colon and rectum, each representing more than 750,000 cases.
*Non-Hodgkin’s lymphoma.
Parkin DM, et al. CA Cancer J Clin. 1999;49:39.

4. Epidemiology Cancer incidence
Males Females
Incidence/ Incidence/ Rank Region 100,000 Region 100,000
1 N. America N. America 277.5
2 Australia/N.Z Australia/N.Z
3 W. Europe N. Europe 234.5
4 Japan S. America* 230.1
5 N. Europe W. Europe 210.4
6 E. Europe Micronesia/ Polynesia
7 S. Europe Southern Africa 187.8
8 S. America* Melanesia 185.6
9 Southern Africa S. America† 185.0
10 Eastern Asia‡ Central America 180.1
Epidemiology: Cancer Incidence by World Region
The incidence of cancers is known to vary substantially from one world region to another. North America and Australia/New Zealand, for example, have incidences of cancers among both males and females that are considerably higher than in other developed regions. In contrast, Northern and Western Africa and many parts of Asia have the lowest cancer incidences.
*Temperate South America.
†Tropical South America.
‡Other than Japan or China.
Parkin DM, et al. CA Cancer J Clin. 1999;49:43.

5. Epidemiology Evolution of cancer death rates, males80 70 60 50 40 30 20 10
Year
Pancreas
Lung & Bronchus
Prostate
Stomach
Colon & Rectum
Leukemia
Liver
1930
1940
1950
1960
1970
1980
1990
1997
Rate per 100,000 Male Population
Epidemiology: Evolution of Cancer Death Rates, Males
Cancer death rates in one developed country, the United States, have shown dramatic changes over the past several decades. Age-adjusted death rates due to cancers of the lung and bronchus, for example, nearly doubled from 1960 through 1996, before declining thereafter. In contrast, death rates due to stomach cancer declined markedly over this time.
Greenlee RT, et al. CA Cancer J Clin. 2001;51:15-36.

6. Epidemiology Evolution of cancer death rates, females80 70 60 50 40 30 20 10
Year
Pancreas
Lung & Bronchus
Prostate
Stomach
Colon & Rectum
Leukemia
Liver
1930
1940
1950
1960
1970
1980
1990
1997
Rate per 100,000 Male Population
Epidemiology: Evolution of Cancer Death Rates, Females
The most marked changes in cancer death rates among women in one developed country, the United States, over the past several decades were observed in cancers of the lung and bronchus, stomach, uterus, and colon and rectum. Whereas age-adjusted death rates due to lung cancer more than tripled among women from 1960 through 1996, deaths due to cancers of the stomach, uterus, and colon and rectum have declined steadily.
Greenlee RT, et al. CA Cancer J Clin. 2001;51:15-36.

7. Epidemiology Mortality for leading cancers in 2001
Males by Age (years), US
All Ages
Lung & bronchus
91,399
Prostate
32,203
Colon & rectum
28,024
Pancreas
13,806
NHL
12,205
20-39
Leukemia
663
Brain & ONS*
627
NHL†
612
484
404
60-79
59,377
15,742
15,615
8,070
6,341
> 80
16,011
15,373
7,455
Bladder
3,034
2,945
40-59
15,521
4,539
2,671
2,399
Esophagus
2,141
Epidemiology: Mortality for Leading Cancers (Males)
Mortality due to different cancer types among males is known to vary by age. Cancers of the lung and bronchus, which are the most common cause of cancer death among males in the United States, are relatively uncommon among men 20 to 39 years of age, but are the most common cause of cancer death among men 40 to 59 and 60 to 79 years of age. Similarly, prostate cancer is uncommon in younger men, but emerges as the second most common cause of cancer death among men 60 to 79 years of age and men over the age of 80.
*Other nervous system.
† Non-Hodgkin’s lymphoma.
Greenlee RT, et al. CA Cancer J Clin. 2001;51:15-36.

8. Epidemiology Mortality for leading cancers in 2001
All Ages
Lung & bronchus
63,075
Breast
41,737
Colon & rectum
28,950
Pancreas
14,529
Ovary
13,391
20-39
1,604
Uterine cervix
634
Leukemia
456
442
Brain & ONS*
401
60-79
39,077
18,292
12,950
7,454
7,038
> 80
13,392
12,174
9,949
5,193
NHL†
3,881
40-59
11,889
10,155
3,472
2,841
1,775
Females by Age (years), US
Epidemiology: Mortality for Leading Cancers (Females)
Cancer mortality among women is known to vary by age for different cancer types. Breast cancer is the most common cause of cancer mortality among women 20 to 39 and 40 to 59 years of age. However, cancers of the lung and bronchus are the most common causes of cancer deaths in women 60 to 79 years of age and in women over the age of 80.
*Other nervous system.
† Non-Hodgkin’s lymphoma.
Greenlee RT, et al. CA Cancer J Clin. 2001;51:15-36.

9. Epidemiology Male cancer statistics
Estimated incidence Estimated deaths
Melanoma of skin
Oral cavity & pharynx
Lung & bronchus
Pancreas
Kidney
Colon & rectum
Prostate
Urinary bladder
Leukemia
Non-Hodgkin’s lymphoma
All others 5% 3%
14% 2%
10%
31% 6%
18%
Esophagus
Lung & bronchus
Pancreas
Liver
Kidney
Colon & rectum
Prostate
Urinary bladder
Leukemia
Non-Hodgkin’s lymphoma
All others 3%
31% 5%
10%
11% 4%
22%
Epidemiology: Male Cancer Statistics
The estimated incidence of various cancer types and number of cancer deaths due to these cancers among men in the United States are shown in this table. Whereas, prostate cancer is the most common cancer type among males, representing 31% of all cancers, cancers of the lung and bronchus are the most common causes of cancer deaths among men, accounting for 31% of all cancer deaths.

10. Epidemiology Female cancer statistics
Estimated incidence Estimated deaths
Melanoma of skin
Thyroid
Breast
Lung & bronchus
Pancreas
Colon & rectum
Ovary
Uterine corpus
Urinary bladder
Non-Hodgkin’s lymphoma
All others 4% 2%
31%
13%
11% 6%
21%
Brain
Breast
Lung & bronchus
Pancreas
Stomach
Colon & rectum
Ovary
Uterine corpus
Non-Hodgkin’s lymphoma
Leukemia
All others 2%
15%
25% 6%
11% 5% 4%
23%
Epidemiology: Female Cancer Statistics
The estimated incidence of various cancer types and the estimated number of cancer deaths due to these cancers among women in the United States are shown in this slide. Breast cancer, which accounts for 31% of all cancers in these women, is implicated in 15% of cancer deaths. In contrast, cancers of the lung and bronchus account for 13% of cancers but are implicated in 25% of cancer deaths.

11. Epidemiology Known causes of cancer
Environmental factors
Occupational exposure to carcinogens
Lifestyle factors
Biologic agents
Pharmacologic/Iatrogenic factors
Epidemiology: Known Cancer Causes
A number of exogenous factors are well known to cause cancer in exposed persons. Much has been written about occupational exposure to a broad array of carcinogens, such as benzene, asbestos, and polychlorinated biphenyls though such exposure has been considerably reduced in developed regions of the world. Lifestyle choices such as diet, consumption of tobacco and/or alcohol, and exposure to biologic agents, such as the hepatitis B or C viruses or the Epstein-Barr virus, have also been demonstrated to lead to the development of cancer. Iatrogenic factors, such as the use of some pharmaceutical agents or ionizing radiation, may also contribute to the development of some cancers.

12. Epidemiology Alcohol-related cancers
Cancer of the esophagus
Head and neck cancer
Liver cancer
Breast cancer
Epidemiology: Alcohol-Related Cancers
Alcoholic beverages have been judged by IARC (WHO) as a lifestyle factor linked to cancer in the esophagus, oral cavity, pharynx, larynx, and liver. Alcohol is also considered a risk factor for breast cancer, but studies have not yet conclusively demonstrated a plausible mechanistic process between alcohol consumption and breast cancer.

13. Epidemiology Alcohol-related cancers
Major cause
Lung
Larynx
Oral cavity
Esophagus
Contributory factor
Pancreas
Bladder
Kidney
Stomach
Uterine cervix
Epidemiology: Smoking-Related Cancers
Overall, cigarette smoking has been identified as the chief preventable cause of deaths due to cancer in the United States. It is a major cause of cancers of lung, larynx, oral cavity, and esophagus, and is considered a contributory factor in pancreatic, bladder, kidney, stomach, and uterine cervix cancers.

14. Epidemiology Virus-related cancers
Agents
Hepatitis B
Hepatitis C
HIV-1
HTLV-1
HPV
Epstein-Barr
Site of Cancer
Liver
Kaposi’s sarcoma
Adult T-cell lymphoma
Uterine cervix
Burkitt’s lymphoma, nasopharynx, Hodgkin lymphoma
Epidemiology: Virus-Related Cancers
Overwhelming evidence shows that chronic infection with hepatitis B is an important cause of hepatocellular carcinoma (HCC)—the most common primary liver cancer. Epidemiologic studies have shown hepatitis C to also be conclusively linked to HCC. HTLV-1 has been implicated in adult T-cell leukemia, whereas HIV type 1 causes Kaposi’s sarcoma. HPV is likely to be an important determinant of cervical cancer, and strong evidence also indicates that Epstein-Barr virus is a causal factor of Burkitts’ lymphoma, cancer of the nasopharynx, and Hodgkin’s disease.
Cole P, Rodu B. Cancer: Principles & Practice ofOncology. 6th ed. 2001;

15. Epidemiology Bacterial-related cancers
Agents
Helicobacter pylori
Schistosoma haematobium
Opisthorchis viverrini
Site of Cancer
Stomach, Pancreas (?)
Urinary bladder
Liver
Epidemiology: Bacterial-Related Cancers
In Asia, a more rare histologic type of liver cancer, cholangiocarcinoma, has been linked to infestation by Opisthorchis viverrini. Other studies have suggested that gastric infection with the bacterium Helicobacter pylori is an important risk factor for gastric cancer. In parts of Africa and the Middle East, infection with the bladder parasite Schistosoma haematobium plays a major role in the causation of bladder cancer.
Ullrich RL, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

16. Epidemiology Pharmacologic/iatrogenic causes of cancer I
Agents
Ionizing radiation
Site of Cancer
Breast cancer
Leukemia
Skin cancer
Thyroid cancer
Lung cancer
Epidemiology: Pharmacologic/Iatrogenic Contributors
The relation between ionizing radiation and breast cancer is well established, with preadolescent exposure greatly increasing the risk of radiation-induced breast cancer. Low doses of ionizing radiation may cause childhood leukemia, and high doses have consistently been found to be leukemogenic. Radiation also has been implicated in the subsequent development of skin cancer, thyroid cancer, and lung cancer.
Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

17. Epidemiology Pharmacologic/iatrogenic causes of cancer II
Pharmaceuticals
Agents Site of Cancer
Chemotherapeutic drugs Bone marrow
Immunosuppressive drugs Reticuloendothelial system
Exogenous hormones Nonsteroidal estrogens Vagina, breast, testis Steroidal estrogens Endometrium Oral contraceptives Liver, endometrium Tamoxifen Endometrium
Phenacetin analgesics Kidney, pelvis, bladder
Epidemiology: Pharmacologic/Iatrogenic Contributors (cont’d)
A number of pharmaceutical agents have been determined to be human carcinogens. Cancer chemotherapeutic drugs have been linked to bone marrow cancer, while immunosuppressive drugs have been shown to have a carcinogenic effect on the reticuloendothelial system. Nonsteroidal estrogens have been implicated in cancer of the vagina, breast, and testes, whereas steroidal estrogens and tamoxifen increase the risk of endometrial cancer. Increased risks of both endometrial and liver cancer have been documented among oral contraceptive users. Finally, phenacetin analgesics are implicated in the cause of kidney and pelvis cancer.
Costanza ME, et al. American Cancer Society Textbook of Clinical Oncology. 3rd ed. 2001;55-74.

18. Epidemiology Occupational-related cancers
Selected Industries Associated with Exposure to Carcinogens
Industry Carcinogen Cancer
Shipbuilding, demolition, insulation Asbestos Lung, pleura, skin
Varnish, glue Benzene Leukemia
Pesticides, smelting Arsenic Lung, skin, liver
Mineral refining and manufacturing Nickel, chromium Lung, nasal passage
Furniture manufacturing Wood dusts Nasal passages
Petroleum products Polycyclic hydrocarbons Lung
Rubber manufacturing Aromatic amines Bladder
Vinyl chloride Vinyl chloride Liver
Radium Radium Lung, bone
Outdoor occupations Ultraviolet light Skin
Epidemiology: Occupational-Related Cancers
The American Cancer Society estimates that approximately 20,000 deaths in the United States can be attributed to occupational exposure to carcinogens. This slide lists occupational cancers by industry and carcinogen.
Bale AE, Brown SJ. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

19. Epidemiology Genetic risk factors: mechanisms of cancer predisposition
Germline tumor suppressor gene inactivation
Germline oncogene activation
DNA repair defects
Ecogenetic traits
Abnormal tissue architecture
Humoral tumor promoters and regressors
Epidemiology: Genetic Risk Factors: Characteristics of Cancer Families
Expression of hereditary cancers may be observed in at least some members of families that have a history of cancer. Cancers in individuals within these families often manifest relatively early in life, possibly in the form of birth defects, and may appear as multiple and bilateral tumors. Hereditary cancers may include rare tumor types, such as retinoblastoma or breast cancer in males, may affect multiple body systems, and may be revealed with variable expressivity among members of the family.
Bale AE, Brown SJ. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

20. Epidemiology Genetic risk factors: characteristics of cancer families
Family history of cancer
Cancer appears relatively early
Multiple and bilateral tumors
May include rare tumor types (eg, retinoblastoma)
Multifocal involvement
Epidemiology: Genetic Risk Factors: Characteristics of Cancer Families
Expression of hereditary cancers may be observed in at least some members of families that have a history of cancer. Cancers in individuals within these families often manifest relatively early in life, possibly in the form of birth defects, and may appear as multiple and bilateral tumors. Hereditary cancers may include rare tumor types, such as retinoblastoma or breast cancer in males, may affect multiple body systems, and may be revealed with variable expressivity among members of the family.
Bale AE, Brown SJ. Cancer: Principles & Practice of Oncology. 6th ed. 2001;

21. Epidemiology Genetic risk factors: Familial cancer syndromes
Familial Cancer Syndrome Site of Cancer
Neurofibromatosis type 1 CNS, neurofibrosarcomas, pheochromocytomas, leukemia
Neurofibromatosis type 2 CNS, spine von Hippel-Lindau disease CNS, renal cell, spine, pancreas, adrenal glands
Li-Fraumeni syndrome CNS, breast, head and neck, soft tissue, osteosarcoma, adrenal cortical carcinomas, leukemia
Wilms’ tumor gene Wilms’ tumor
Basal cell carcinoma syndrome Skin, CNS, ovary
Epidemiology: Genetic Risk Factors: Familial Cancer Syndromes
A number of familial cancer syndromes have been identified. These typically rare syndromes include neurofibromatosis Types 1 and 2, von Hippel-Lindau disease, hereditary Wilms’ tumor and related syndromes, Li-Fraumeni syndrome, and nevoid basal cell carcinoma syndrome.
Bale AE, Li FP. Cancer: Principles & Practice of Oncology. 5th ed. 1997;
Linehan WM, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;

22. Epidemiology Genetic risk factors: Familial cancer syndromes
Familial Cancer Syndrome Site of Cancer
Familial adenomatous polyposis coli Colorectal, jaw, skull, skin, stomach, CNS
Hereditary nonpolyposis colorectal Colorectal cancer
Cowden’s syndrome Thyroid, stomach, breast, ovary
BRCA-1 Breast, ovary
BRCA-2 Breast (female and male)
Epidemiology: Genetic Risk Factors: Familial Cancer Syndromes (cont’d)
Other familial cancer syndromes include familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Cowden’s syndrome, and cancers associated with the presence of the BRCA-1 and BRCA-2 genes.
Bale AE, Li FP. Cancer: Principles & Practice of Oncology. 5th ed. 1997;
Safai B. Cancer: Principles & Practice of Oncology. 5th ed. 1997;
Cohen AM, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;
Dickson RB, Lippman ME. Cancer: Principles & Practice of Oncology. 5th ed. 1997;

23. Epidemiology Reducing mortality
The National Cancer Institute estimates that cancer mortality rates could be significantly reduced, as follows:
8% to 16% by a 15% decrease in tobacco use among adults
8% by dietary measures
3% by early screening and early detection
% by wider application of state-of-the art treatment
Epidemiology: Reducing Mortality
An estimated one in three Americans will have cancer over the course of his or her lifetime. However, the National Cancer Institute suggests that a substantial reduction in cancer mortality could be achieved through the following measures: control of tobacco use, widespread adoption of a low-fat diet with greatly increased fiber consumption, early detection and screening, and the wider application of state-of-the art treatments.
Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;40-63.

24. Epidemiology Risk reduction
Relative risk = risk of developing a disease in the population exposed to a risk factor, divided by the risk of developing that same disease among those not exposed to that same risk factor
Population attributable risk = the percentage by which the disease could reduced if exposure to the risk factor was eliminated
Epidemiology: Risk Reduction
The elimination of exposure to risk factors is the focus of cancer primary prevention efforts. The relative risk for a particular type of cancer describes the greater risk of the population exposed to the risk factor compared to those not exposed. For example, the relative risk of developing lung cancer is 11 for smokers, meaning that the relative risk is 11 times greater for smokers than nonsmokers. The population attributable risk describes the percentage of cancer cases that could be eliminated by eliminating exposure to the risk factor. For example, it is estimated that 87% of the lung cancer cases could be eliminated by eliminating exposure to smoking.
Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;40-63.

25. Epidemiology Modifiable risk factors I
Site of Relative Attributable Cancer Risk Factor Risk Risk
Lung Cigarette smoking Strong 87%
Occupation Strong 13%
Residential radon exposure Moderate 10%
Second-hand smoke Weak 2%
Diet low in beta carotene Weak -
Dietary fat/low-vegetable diet Possible 5%
Urban air pollution Possible -
Colorectal High-fat/low-vegetable diet Weak 50%
Physical inactivity Weak 20%
Occupation Weak -
Obesity Weak -
Epidemiology: Modifiable Risk Factors
This slide lists the modifiable risk factors for lung and colorectal cancers, along with the magnitude of the relative risk and the best available estimate of attributable risk for these cancers.
Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;40-63.

26. Epidemiology Modifiable risk factors II
Site of Relative Attributable Cancer Risk Factor Risk Risk
Breast First full-term pregnancy after age 30 Moderate 7%
Large doses of chest irradiation Moderate 2%
Never married Weak -
Never having children Weak 5%
Post-menopausal obesity Weak 12%
Alcohol consumption Weak -
High fat Possible -
Low physical activity Possible -
Use of diethylstilbestrol Possible -
Use of oral contraceptives or ERT Possible -
Epidemiology: Modifiable Risk Factors (cont’d)
This slide lists the modifiable risk factors for breast cancer, along with the magnitude of the relative risk and the best available estimate of attributable risk for this cancer.
Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;40-63.

27. Epidemiology Modifiable risk factors III
Site of Relative Attributable Cancer Risk Factor Risk Risk
Cervix Multiple sex partners Moderate 38%
Early age at first intercourse Moderate 25%
History of STD Moderate 5%
Cigarette smoking Weak 32%
Use of barrier contraceptives Weak -
Low dietary intake of vitamin A, Weak - beta-carotene, and folate
Epidemiology: Modifiable Risk Factors (cont’d)
This slide lists the modifiable risk factors for cancer of the cervix, along with the magnitude of the relative risk and the best available estimate of attributable risk for this cancer.
Bal DG, et al. American Cancer Society Textbook of Clinical Oncology. 2nd ed. 1995;40-63.

28. Asymptomatic People (Average Risk)
Epidemiology ACS Screening Recommendations for Colorectal, Prostate, Cervical, and Breast Cancer
Asymptomatic People (Average Risk)
Test/Procedure Sex Age Frequency
Colorectal cancer screening M&F >50 Annual FOBT, flexible sigmoidoscopy every 5 years, or both; colonoscopy every 10 years; or
double-contrast barium enema every 5 years
PSA test + rectal exam M >50 Every year if life expectancy > 10 years
Pap test F >18* Every year, if normal >3 times, Pap test may be performed less frequently at discretion of physician
Pelvic exam F >18* Every year
Breast self-exam F >20 Every month
Breast clinical exam F Every 3 years >40 Every year
Mammography F >40 Every year
Counseling and cancer M&F Every 3 years checkups >40 Every year
Epidemiology: Early Detection Guidelines
This slide lists the American Cancer Society’s guidelines for early detection of selected cancers in both men and women.
* Or before if sexually active.
† At menopause, for women at high risk for endometrial cancer due to history of infertility, obesity, failure to ovulate, abnormal uterine bleeding, unopposed ERT or tamoxifen use.
Smith RA, et al. CA Cancer J Clin 2001;51:38-75.