1. 1 Cancer Etiology Dan Aderka MD 3.12.2007

2. Molecular mechanisms Environment Cancer cells

11. Cancer = 246244 17.7% Heart diseases = 463754 33.4% Above 75= 1.388.730

13. Male cancer statistics Adapted from Greenlee RT, et al. CA Cancer J Clin. 2000;51:18, 15-36. Estimated incidenceEstimated 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% 10% 11% 3% 4% 5% 22% 13

14. 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 deaths 14

15. What is cancer? What are the etiological causes of cancer? Why it appears ? How it appears? How to treat cancer?

17. Environmental factors Occupational exposure Lyfestyle factors Biologic agents Pharmacologic factors Genetic factors

18. Environmental factors Occupational exposure Lyfestyle factors Biologic agents Pharmacologic factors Genetic factors

19. Meat intake

20. Low intake of folic acid

21. Folic acid Dihydro-folate (DHF) Tertra-hydro-folate (THF) N 5 N 10 methylene THF dTDP dTTP DNA dUMP dTMP Thymidilate synthase CACTACA CACUACA dUDP dUTP CAC UACA DNA brake

25. Major cause Lung Larynx Oral cavity Esophagus Contributory factor Pancreas Bladder Kidney Stomach Uterine cervix Smoking-related cancers Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;241-252.

27. 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.

28. Low intake of vegetables

29. Environmental factors Occupational exposure Lyfestyle factors Biologic agents Pharmacologic factors Genetic factors

30. Selected Industries Associated with Exposure to Carcinogens IndustryCarcinogenCancer Shipbuilding, demolition, insulation AsbestosLung, pleura, skin Varnish, glue BenzeneLeukemia Pesticides, smelting ArsenicLung, skin, liver Mineral refining and manufacturingNickel, chromium Lung, nasal passages Furniture manufacturing Wood dustsNasal passages Petroleum products Polycyclic hydrocarbonsLung Rubber manufacturing Aromatic aminesBladder Vinyl chloride Vinyl chlorideLiver Radium RadiumLung, bone Outdoor occupations Ultraviolet lightSkin Occupational-related cancers Costanza ME, et al. American Cancer Society Textbook of Clinical Oncology. 3rd ed. 2001;55-74.

31. Environmental factors Occupational exposure Lyfestyle factors Biologic agents Pharmacologic factors Genetic factors

32. APC

33. Colon cancer genetics 33 Hereditary colon cancersMutated gene Hereditary non polyposis colorectal cancer MSH2, MLH1, PMS1,PMS2, etc. FAPFamilial adenomatous polyposis APC Turcot syndrome (+ medulloblastomas ) APC Gardner syndrome ( osteomas, desmoid tumors, epidermoid cysts, polyposis) APC Supernumerary and unerupted teeth

34. BRCA1 BRCA2 Breast and ovarian cancer

35. Von Hippel Lindau (VHL) gene

36. Neurofibromatosis Sarcoma

38. Environmental factors Occupational exposure Lyfestyle factors Biologic agents Pharmacologic factors Genetic factors

39. Agents Hepatitis B Hepatitis C HIV-1 HTLV-1 HPV Epstein-Barr Virus-related cancers Site of Cancer 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

40. Agents Helicobacter pylori Schistosoma haematobium Opisthorchis viverrini Bacterial-related cancers Site of Cancer Stomach Urinary bladder Liver Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;241-252. 40

41. Environmental factors Occupational exposure Lyfestyle factors Biologic agents Pharmacologic factors Genetic factors

42. Pharmaceuticals AgentsSite of Cancer Cancer chemotherapeutic drugsBone marrow Immunosuppressive drugsReticuloendothelial system Exogenous hormones Nonsteroidal estrogensVagina, breast, testis Steroidal estrogensEndometrium Oral contraceptivesLiver, endometrium TamoxifenEndometrium Phenacetin analgesicsKidney, pelvis, bladder Adapted from Cole P, Rodu B. Cancer: Principles & Practice of Oncology. 6th ed. 2001;241-252.

43. Environmental factors Occupational exposure Lyfestyle factors Biologic agents Pharmacologic factors Genetic factors

44. Ullrich RL, et al. Cancer: Principles & Practice of Oncology. 6th ed. 2001;195-206. Agent Ionizing radiation Type of Cancer Breast cancer Leukemia Skin cancer Thyroid cancer Lung cancer 44 Ultraviolet light

45. All the presented information can help us for cancer prevention. Oncology deals with established cancer ! Let’s see what is cancer !