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Cancer Etiology

Dan Aderka MD 3.12.2007

Molecular mechanisms

Environment

Cancer cells

Cancer = 246244 17.7%

Heart diseases = 463754 33.4%

Above 75= 1.388.730

5

10

15

20

25

30

35

40%

of

tota

l M

ort

ali

ty

25 30 35 40 45 50 55 60 65 70 75 80 85

Age

Cancer and heart disease relative mortality in 2002 (USA)

Heart disease

Cancer

Male cancer statistics

Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000;51:18, 15-36.

Estimated incidenceEstimated incidence Estimated deathsEstimated 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%

3%

10%

31%

6%

3%

5%

18%

Esophagus

Lung & bronchus

Pancreas

Liver

Kidney

Colon & rectum

Prostate

Urinary bladder

Leukemia

Non-Hodgkin’s lymphoma

All others

3%

31%

5%

3%

3%

10%

11%

3%

4%

5%

22%

13

Female cancer statistics

Adapted from Greenlee RT, et al. CA Cancer J Clin. 2001;51:18, 15-36.

2%

15%

25%

6%

2%

11%

5%

2%

5%

4%

23%

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%

2%

11%

4%

6%

2%

4%

21%

Brain

Breast

Lung & bronchus

Pancreas

Stomach

Colon & rectum

Ovary

Uterine corpus

Non-Hodgkin’s lymphoma

Leukemia

All others

Estimated incidenceEstimated incidence Estimated deathsEstimated deaths

14

What is cancer?

What are the etiological causes of cancer?

Why it appears ?

How it appears?

How to treat cancer?

Environmental factors

Occupational exposureLyfestyle factors

Biologic agents

Pharmacologic factorsGenetic factors

Environmental factors

Occupational exposureLyfestyle factors

Biologic agents

Pharmacologic factorsGenetic factors

Meat intake

Low intake of folic acid

Folic acid

Dihydro-folate (DHF)

Tertra-hydro-folate (THF)

N5N10 methylene THFdTDP

dTTPDNA

dUMP

dTMP

Thymidilate synthase

CACTACA

CACUACAdUDP

dUTP

CAC UACA

DNA brake

QuickTime™ and aTIFF (LZW) decompressor

are needed to see this picture.

Major causeMajor cause• Lung• Larynx• Oral cavity• Esophagus

Contributory factorContributory factor• Pancreas• Bladder• Kidney• Stomach• Uterine cervix

Smoking-related cancers

Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;241-252.

• Cancer of the esophagus

• Head and neck cancer

• Liver cancer

• Breast cancer

Alcohol-related cancers

Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;241-252.Winer E, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;1651-1717.

Low intake of vegetables

Environmental factors

Occupational exposureLyfestyle factors

Biologic agents

Pharmacologic factorsGenetic factors

Selected Industries Associated with Exposure to CarcinogensSelected Industries Associated with Exposure to Carcinogens

IndustryIndustry CarcinogenCarcinogen CancerCancer

Shipbuilding, demolition, insulation Asbestos Lung, pleura, skin

Varnish, glue Benzene Leukemia

Pesticides, smelting Arsenic Lung, skin, liver

Mineral refining and manufacturing Nickel, chromiumLung, nasal passages

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

Occupational-related cancers

Costanza ME, et al. American Cancer Society Textbook of Clinical Oncology. 3rd ed. 2001;55-74.

Environmental factors

Occupational exposureLyfestyle factors

Biologic agents

Pharmacologic factorsGenetic factors

APC

Colon cancer genetics

33

Hereditary colon cancers Mutated gene

Hereditary non polyposis colorectal cancer MSH2, MLH1,PMS1,PMS2, etc.

FAP Familial adenomatous polyposis APC

Turcot syndrome (+ medulloblastomas)

APC

Gardner syndrome (osteomas, desmoid tumors, epidermoid cysts, polyposis)

APC

Supernumerary and unerupted teeth

BRCA1

BRCA2

Breast and ovarian cancer

Von Hippel Lindau (VHL) gene

Neurofibromatosis

Sarcoma

Environmental factors

Occupational exposureLyfestyle factors

Biologic agents

Pharmacologic factorsGenetic factors

AgentsAgents

• Hepatitis B

• Hepatitis C

• HIV-1

• HTLV-1

• HPV

• Epstein-Barr

Virus-related cancers

Site of CancerSite of Cancer

Liver

Liver

Kaposi’s sarcoma

Adult T-cell lymphoma

Uterine cervix

Burkitt’s lymphoma, nasopharynx,Hodgkin’s disease

Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;241-252.39

AgentsAgents

Helicobacter pylori

Schistosoma haematobium

Opisthorchis viverrini

Bacterial-related cancersSite of CancerSite of Cancer

Stomach

Urinary bladder

Liver

Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;241-252.40

Environmental factors

Occupational exposureLyfestyle factors

Biologic agents

Pharmacologic factorsGenetic factors

PharmaceuticalsPharmaceuticals

AgentsAgents Site of CancerSite of Cancer

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

Adapted from Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;241-252.

Environmental factors

Occupational exposureLyfestyle factors

Biologic agents

Pharmacologic factorsGenetic factors

Ullrich RL, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;195-206.

AgentAgent

Ionizing radiation

Type of CancerType of Cancer

Breast cancer

Leukemia

Skin cancer

Thyroid cancer

Lung cancer

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Ultraviolet light

All the presented information can help us for cancer prevention.

Oncology deals with established cancer !

Let’s see what is cancer !