Various aetological factors in causation of Tumours or Neoplasms.

2. Incidence Of Cancer
• Cancer is one of the most common diseases in the
developed world:
• 1 in 4-5 deaths are due to cancer
• 1 in 17 deaths are due to lung cancer
• Lung cancer is the most common cancer in men
• Breast cancer is the most common cancer in women
• There are over 100 different forms of cancer

3. INCIDENCE
• Worldwide—20% of all Death are from Cancer,
• In U.S.-2nd most common cause of death,next to Heart-Dis.
• Most Common Cancers: are:
In Developed Countries : Lung,Breast,Prostate,Colorectal
In DevelopingCountries:Oral&esophageal,Cervix,Breast,Liver
Geographic & Environmental Factors:
 Sun exposure
 Melanomas 6x incidence New Zealand vs Iceland
 Blacks have low incidence of melanoma
 Smoking and alcohol abuse
 Body mass
 Overweight = 50% increase in cancer
 Environmental vs racial factors
 Japanese immigrants to USA

6. I.Predisposing (Epidemiological Risk)Factors for Cancers:include
-a) Endogenous ( Constitutional ) Host Factors,
& b) Exogenous Environmental Factors
II.Precipitating Carcinogenesis Factors, encompassing Exogenous
Agents like: - PHYSICAL
- CHEMICALS
- BIOLOGICALS
 Age:
-Most cancers occur in Older persons > 55 years
-Childhood cancers:Leukemias & CNS neoplasms,Bone tumors like EWINGS’
BLASTOMAS.
SEX:Certain tumors are more common in particular sex.either Male or Females,
- In MALES : Lungs, Prostate, Oral, Colorectal
- In FEMALES:Breast, Cervix in Indians No.1,Gall Bladder,Thyroid,Hypopharynx
RACE:White Europeans & Americans: Lung, Breast, & Colorectals,
Blacks : Lungs,Liver,Prostate,Penis
Japanese : Ca.-Stomach 5 times> Americans
South-East Asians: esp. Chinese- Nasopharyngeal Ca.
Indians:Oral,Upper aerodigestive,Liver –Due to HBV,HBC., F- Ca.Cx.,Breast
Heredity or Genetic Factors : Retinoblastoma,FPCor APC,MEN ,etc.

7. PREDISPOSING FACTORS
OR
EPIDEMIOLOGICAL RISK FACTORS:
Are :1.AGE,
 2.SEX,
 3.RACE,
 4.HEREDITY or GENETIC Factors
 5.Environmental & Cultural Factors,
 6.Certain Precursor Lesions

8. 1.AGE - Distribution-Most cancers occur in Older persons > 55 years
-Childhood cancers:Leukemias & CNS neoplasms
(2%) Bone tumors like EWINGS’
BLASTOMAS

11. 2.SEX-Distribution
Certain tumors are more common in particular
sex.either Male or Females,
- In MALES : Lungs, Prostate, Oral, Colorectal >
- In FEMALES:Breast, Cervix in Indians No.1,Gall-
Bladder,Thyroid,Hypopharynx

13. 3.RACE- Distribution
White Europeans & Americans: Lung, Breast, &
Colorectals,
 Blacks : Lungs,Liver,Prostate,Penis
 Japanese : Ca.-Stomach 5 times> Americans
 South-East Asians: esp. Chinese-
Nasopharyngeal Ca.
 Indians:Oral,Upper-aerodigestive,Liver –Due
to HBV,HBC.,
In Indians Females- Ca.Cervix,Breast >

14. Genetic predispostion or HEREDITY
 Early age at onset
 Two or more primary relatives with
-the cancer
 Multiple or bilateral tumors
 Polymorphisms that metabolize
procarcinogens, e.g., nitrites
4.HERIDITY or Genetic Predisposition

16. Hereditary Risk:Genes Involved in Restraining Cell Proliferation

17. 5.ENVIRONMENTAL & CULTURAL FACTORS

19.  1.Nonhereditary predisposing conditions
2.Precancerous Conditions
3.Chronic Inflammations
4.Chronic ulcerative colitis
5.Atrophic gastritis of pernicious anemia
6Leukoplakia of mucous membranes
7.Immunodeficiency: like T-cell deficiency-
Lymphoma& Ca.- in HIV-AIDS,
Kaposi-Sarcoma
6. Certain Precursor Lesions : like

20. Examples Of Acquired Premalignant Lesions &Conditions

22. PRECIPITATING FACTORS
• PHYSICAL FACTORS
• CHEMICAL FACTORS
• BIOLOGICAL FACTORS

23. PHYSICAL CARCINOGENESIS
•Radiation
–ultraviolet light & ionising radiations like X-rays, α-, β-
& γ-rays, radioactive isotopes, protons & neutron
–Higher dose and with high LET (linear energy transfer)
caused carcinogenic effect
•Non-radiation
–Continous mechanical injury to the tissues such as
from intrinsic stone
–implants of inert materials such as plastic, glass etc in
prostheses
PHYSICAL FACTORS

24. RADIATION CARCINOGENS
UV: BCC, SCC, MM
 IONIZING: photons and particulate
 Hematopoetic and Thyroid (90%/15yrs)
tumors in fallout victims
 Solid tumors either less susceptible or require a
longer latency period than LEUK/LYMPH
 BCCs in Therapeutic Radiation

25. CHEMICAL FACTORS
• Chemical Carcinogens

27. Chemical carcinogens and chemical carcinogenesis
•Chemical carcinogens can be classified into :
•DIRECT-ACTING CARCINOGENS: do not require metabolic activation
1.–Alkylating Agents: various anti-cancer drugs (e.g.
cyclophosphamide, chlorambucil, busulfan, melphalan,
nitrosoureaetc), β-propiolactoneand epoxides.
2.–Acylating Agents: acetyl imidazole & dimethylcarbamylchloride
•INDIRECT-ACTING CARCINOGENS (PROCARCINOGENS): prior
metabolic activation before becoming potent carcinogens.
1.–Polycyclic aromatic hydrocarbons: Anthracenes, Benzapyrene,
Methylcholanthrene
2.–Aromatic amines and azo-dyes: β-naphthylamine, Benzidine
3.–Naturally-occurring products: AflatoxinBl, ActinomycinD,
MitomycinC, Safrole, Betel nut
4.–Miscellaneous: Nitrosamines and nitrosamides, Vinyl chloride
monomer, Asbestos, Saccharin & Cyclomates,

30. CHEMICAL CARCINOGENS:
INITIATORS
• DIRECT
• β-Propiolactone
• Dimethyl sulfate
• Diepoxybutane
• Anticancer drugs
(cyclophosphamide,
chlorambucil,
nitrosoureas, and others)
• Acylating Agents
• 1-Acetyl-imidazole
• Dimethylcarbamyl chloride
• “PRO”CARCINOGENS
• Polycyclic and Heterocyclic
• Aromatic Hydrocarbons
• Aromatic Amines, Amides,
• Azo Dyes
• Natural Plant and Microbial
Products:
Aflatoxin B1- Hepatomas
Griseofulvin- Antifungal
Cycasin- from cycads
Safrole - from sassafras
Betel nuts- Oral SCC

31. CHEMICAL CARCINOGENS:(contd.)
INITIATORS
OTHERS
Nitrosamine and amides (tar, nitrites)
Vinyl chloride- angiosarcoma in Kentucky
Nickel
Chromium
Insecticides
Fungicides
Poly Chlorinated Biphenyls (PCBs)

32. CHEMICAL CARCINOGENS:(contd.)
PROMOTORS
 HORMONES
PHORBOL ESTERS (TPA), activate kinase C
 PHENOLS
 DRUGS
“Initiated” cells respond and proliferate
FASTER to promotors than normal cells

35. BIOLOGICAL FACTORS

36. BIOLOGIC CARCINOGENS:
•Parasites: Schistosomahaematobium-squamouscell carcinoma
of the urinary bladder,
–Clonorchissinensis, the liver fluke -cholangiocarcinoma.
•Fungus: Aspergillusflavus(incertaingrains)-hepato cellular Ca.
•Bacteria: Helicobacter pylori -chronic gastritis and peptic ulcer;
its prolonged infection may lead to gastric lymphoma
&gastric carcinoma,
•Viral: most important organisms are :
–OncogenicRNA Viruses : human T-cell leukemia virus-1 (HTLV-1)
, only retrovirus that has been demonstrated to cause cancer in
humans
–OncogenicDNA Viruses : -human papillomavirus(HPV), Epstein-
Barr virus (EBV), Kaposi sarcoma herpesvirus(KSHV) also called
human herpesvirus8), and hepatitis B virus (HBV)

41. CHARLES C COLTON 1820, Lacon1:322
The greatest fool may ask more than the wisest man can answer

44. 2014-Estimated Cancer Incidence By Site & Sex

45. 2014-Estimated Cancer Deaths BySite & Sex