This document discusses various factors that cause cancer. It begins by defining cancer and outlining Hanahan's six hallmarks of cancer. It then provides an outline to discuss tobacco, cancer susceptibility syndromes, DNA/RNA viruses, inflammation, chemical factors, physical factors like radiation, dietary factors, and obesity. Tobacco is identified as the leading cause of cancer, responsible for 25-30% of cases. Diet and physical activity related factors also account for 30-35% of cancers. 60-65% of cancers could be prevented through lifestyle modifications. Vaccines should be emphasized to prevent virus-related cancers, and screening and genetic counseling should target genetically linked cancers like breast and colon.

1. Jaineel Dharod
Dept. of Pharmacology

2. WHAT IS CANCER?
 Cancer, known medically as a
malignant neoplasm, is a broad group
of various diseases, all involving
unregulated cell growth.
 In cancer, cells divide and grow
uncontrollably forming malignant
tumors and invade nearby parts of the
body.
 The cancer may also spread to more
distant parts through lymph or blood.

3. HANAHAN’S SIX HALLMARKS OF CANCER
 Limitless Replicative Potential
 Sustained Angiogenesis
 Evading Apoptosis
 Self Sufficiency in Growth Signals
 Insensitivity to Antigrowth Signals
 Tissue Invasion and Metastasis

4. Indian ICMR Data

6. ROAD MAP FOR DISCUSSION
A. Tobacco (25-30%)
B.Cancer Susceptibility Syndrome (5- 10%)
C. DNA Viruses & RNAViruses
D.Inflammation (15-20%)
E. Chemical Factors
F. Physical Factors (up to 10%)
G. Dietary Factors
H. Obesity and PhysicalActivity

7. A. TOBACCO

8.  There are about 1.2 billion smokers and
hundreds of millions of smokeless
tobacco users.
 Cigarette smoking causes well over 1
million cancer deaths worldwide.
 Lung Cancer is the dominant malignancy.
 19 cancers for which evidence is
considered sufficient that they are caused
by cigarette smoking.
 3 cancers caused by smokeless tobacco

10. CONSTITUENTS OF CIGARETTE SMOKE
CLASSIFIED BY IARC AS CARCINOGENIC
72 compounds listed and 15 are
carcinogenic to humans
 N-Nitrosamines
 Aromatic Amines
 Aldehydes
 Phenolic Compounds
 Nitrohydrocarbons
 Miscellaneous Organic Compounds
 Metals and Inorganic Compounds
 Polycyclic Aromatic Hydrocarbons

11. CONSTITUENTS OF CIGARETTE

12. MECHANISM OF TOBACCO CARCINOGENESIS

13. CARCINOGENS AND TOBACCO-INDUCED CANCERS
Lung PAH, NNK, Isoprene, Aldehydes,
Benzene
Larynx PAH
Nasal NNK, NNN
Oral Cavity PAH, NNK, NNN
Esophagus NNN, Other Nitrosamines
Liver NNK, Other Nitrosamines
Pancreas NNK, NNAL
Cervix PAH, NNK
Bladder AromaticAmines
Leukemia Benzene
Colorectal Heterocyclic AromaticAmines
PAH – Polyaromatic Hydrocarbons ; Nitrosamines - NNN, NNK, NNAL

14. B. CANCER
SUSCEPTIBILITY
SYNDROMES

15.  Some genetic mutations confer such pro-
tumorigenic power that individuals who
harbour them are at extreme risk for cancer
development.
 A large number of proteins that regulate
genomic integrity (caretakers) and critical
tumour suppressors are mutated in cancer
susceptibility syndromes.

16. Hereditary tumorigenesis - One mutant allele is inherited from either parent
Sporadic tumorigenesis - One allele is mutated somatically, in which case there is one
predisposed cell.

17. Regulation of Translation PTEN
LKB1
Cowden Syndrome
Peutz-Jeghers
Syndrome
PTCH 1
Nevoid Basal Cell
Syndrome
Regulation of
Proliferation NF 1 Neurofibromatosis 1
(AD)
APC FamilialAdenomatous
Polyposis (AD)
Genomic Integrity and
Apoptosis BLM Bloom’s Syndrome
TP53 Li-Fraumeni Syndrome
CANCER SUSCEPTIBILITY GENES &
ASSOCIATED SYNDROMES
Function Gene Associated
Syndrome

18. PREVALENT SYNDROMES
 HNPCC/ Lynch Syndrome – Most common CS
disease; Incidence is 1 in 400; AD with 90%
penetrance; Additional Risk of Endometrial
Cancer.
 Hereditary Breast-Ovarian Cancer Syndrome
(HBOC) – BRCA 1 and BRCA 2 mutations; AD
with 85% penetrance.
 NF 1 – AD with 100% penetreance.
 FAP – AD with high penetrance; Germ line
mutation in APC gene on 5q

19. CS SYNDROMES DUE TO PROTO-
ONCOGENE ACTIVATION
 Costello Syndrome – HRAS Gene
 Hereditary Papillary Renal Cancer – MET Gene
 Multiple Endocrine Neoplasia Type 2 – RET Gene
 Hereditary Gastrointestinal Stromal Tumors – KIT
Gene
 Familial Melanoma – CDK4 Gene

20. C. DNA VIRUSES
&
RNA VIRUSES

21. DNA VIRUSES
 Hepadnaviruses
 Papillomaviruses
 Epstein-Barr Virus
 Kaposi’s Sarsoma – Associated
Herpesvirus
 Human Polyomaviruses

22. RNA VIRUSES
 Retroviruses
 HTLV -1
 HTLV -2
 Human Immunodeficiency Virus
 Hepatitis C Virus

23. HUMAN VIRUSES WITH
ONCOGENIC PROPERTIES
Virus Family Type Assoc Tumors Cofactors
Flaviviruses Hepatitis C Hepatocellular Ca -
Hepadnavirus Hepatitis B Hepatocellular Ca Aflatoxin,Alcohol,
Smoking
Herpesviruses EBV Burkitt’s Lymphoma,
Nasopharyngeal
Carcinoma, HL,
Gastric Cancers
Malaria
Nitrosamines
KSHV(HSV8)
Kaposi’s Sarcoma,
Pulmonary Effusion
Lymphoma,
Castleman’s Disease
HIV Infection
Papillomaviruses HPV 16,18 Anogenital Cancers Smoking
Polyomaviruses Merkel Cell
Virus
Merkel Cell
Carcinoma
Immunosuppression
Retroviruses HTLV-1 Adult T Cell
Leukemia
Uncertain

24. D. INFLAMMATION

25. CANCER AND INFLAMMATION
• Chronic inflammation tends to be associated with protumor effects.
• Acute inflammation is associated with an antitumor effect.
• However, this distinction is not absolute.

26. CHRONIC INFLAMMATORY CONDITIONS
ASSOCIATED WITH TUMOR FORMATION
Pathological Condition Associated Tumors Etiological Agent
Sjogren Syndrome,
Hashimoto’s Thyroiditis
Mucosa-assoc lymphoid
tissue lymphomas
-
Reflux esophagitis,
Barrett’s esophagus
Esophageal Carcinoma Gastric acid, Alcoholism,
Smoking
Liver Cirrhosis Hepatocellular Carcinoma Alcoholism
IBD Colorectal carcinoma -
Cystitis, Bladder Bladder Carcinoma Chronic indwelling, urinary
inflammation catheters
Asbestosis, Silicosis Mesothelioma, Lung
Carcinoma
Asbestos fibres, Silica
particles

27. Pathological Condition Associated Tumor Pathogens
Hepatitis HCC Hepatitis B, C
Mononucleosis B cell NHL and Burkitt’s EBV
AIDS NHL, SCC, KS HIV, HHV-8
Warts Skin cancer Papillomaviruses
Gastritis/Ulcers Gastric adenocarcinoma H.Pylori
Chronic Cholecystitis Gall bladder Cancer Bacteria, Gallbladder
Stones
Opisthorchiasis, Cholangitis Cholangiosarcoma, Colon Ca Opisthorchis viverrini,
Opisthorcis sinensis
Chronic Cystitis Bladder, Liver, Rectal Ca,
Follicular lymphoma of
Spleen
S.hematobium,
S.japonicum, Irradiation,
Carcinogens
CANCERS ASSOCIATED WITH INFLAMMATION CAUSED
BY INFECTIOUS AGENTS

28.  Tissue damage and repair .
 Increase in the proliferation rate in the affected tissue.
 Increase in the probability of mutation or chromosomal translocation
during mitosis.

29. E. CHEMICAL FACTORS

30. CHEMICAL CARCINOGENS
Gastric Smoked, salted and
pickled foods
-
Colon Heterocyclic amines,
Asbestos
Pattern Makers
Liver Aflatoxin, vinyl chloride,
alcoholic beverages -
Bladder Tobacco smoke, Benzidine,
Phenacetin
Magenta manufacture,
auramine manufacture
Lung & Pleura Tobacco, Arsenic,
Asbestos, Silica, Coal tar
Aluminum production, coal
gasification, coke
production, hematite
mining, painters,
Oral Cavity Tobacco, Alcoholic, nickel
compounds
Boot and shoe production,
Furniture manufacturer

31. F. PHYSICAL FACTORS

32. • Ionizing radiation
• Ultraviolet Radiation
• RF & Microwave
Radiation
• Electromagnetic
Fields
• Asbestos
• Nanoparticles

33. Hiroshima
and
Nagasaki
Bombs

34.  It has been estimated that 1 Gy of ionizing radiation
gives rise to about 40 DSBs, 1,000 SSBs, 1,000
base lesions, and 150 DNA-protein cross-links per
cell.

36.  RFR and MR do not have sufficient energies to
cause ionizations in target tissues.
 Sources - mobile phones, radars, medical devices,
and kitchen appliances.
 Mobile phones emit radiofrequency radiation (RFR)
and generate EMFs.
 At these intensities, induction of DNA damage has
been detected only in laboratory studies.

38. *#07#
Check SAR
of
Your device
It should be less than
1.6 W/ kg

39. G. DIETARY FACTORS

40. DIET
 Mutagens in foods, due to heating of
proteins, can cause damage to DNA.
 Alcohol - Best established dietary risk factor
 Fat – Cancers of breast, colon, prostate, and
endometrium.
 Red meat - Increased risk of colorectal
cancer.

41. Direct damage in the upper GI tract.
Modulation of DNA methylation.
Acetaldehyde - Enhances proliferation of epithelial cells,
forms DNA adducts, and is a recognized carcinogen.

42.  Fruits and vegetables have been hypothesized in
cancer prevention.
 Contain antioxidants, minerals, fiber, potassium,
carotenoids, vitamin C, folate, and other vitamins.
 Supply less than 5% of total energy intake but
concentration of micronutrients in these foods is
greater than in most others.

43.  Fiber is fermented by the luminal bacteria of the colon.
 Bulking effect ; Reduces colonic transit time, and the binding
of potentially carcinogenic luminal chemicals.
 May also aid in producing short-chain fatty acids that may
be directly anticarcinogenic, and fiber may induce apoptosis.

44. H. OBESITY &
PHYSICAL ACTIVITY

45. Overweight
& Obesity
 Established risk factor for colon cancer in both men and
women.
 Increased physical activity - Protective for colon cancer.
 Impact on insulin sensitivity and IGF profiles, and
inflammation, as well as some colon-specific mechanisms
 Physical activity stimulates stool transit in the colon,
decreasing the exposure of colonic mucosa to carcinogens
Endogenous
Estrogen
levels
Risk of
Endometrial &
Breast
Cancer

46. Gastric
Adenocarcinoma
Gastro esophageal
Reflux symptoms
 Obese &
High BMI
 Obesity, in addition to high blood pressure and diabetes, is
an established risk factor for kidney cancer.
 High BMI and Obesity have also been implicated in various
studies of Gall Bladder Cancer, Pancreatic Cancer, Prostate
Cancer and NHL..

47. • Most common causes of cancer are
Tobacco (25 - 30%), Diet and Physical
Activity related Factors (30-35%).
• 60-65% cancers can be prevented just by
Lifestyle modification.
• Vaccines which can prevent malignancies
should be emphasized and counseled to
parents.
• Genetically related malignancies like Breast
and Colon Cancer should have screening
and Genetic Counseling.

48. Thank
you