1. Pre-neoplastic Disorders
Cancer Epidemiology
Pre-neoplastic Disorders
Carcinogenic Agents
Neoplasia 7
Dr. Faten Ghazal
Professor of Pathology

2. Intended Learning Outcomes (ILOs)
By the end of this lecture YOU will be able to:
Describe some geographic and environmental factors related to some types of cancer
Identify some aspects of cancer incidence related to age & sex
List some inherited cancer syndromes
Relate some pre-neoplastic disorders to their specific type of cancer
List important carcinogenic agents
Define terms of initiation, promotion and progression

3. What is cancer epidemiology? What is its the importance?
Distribution of cancer in population
Its goal is to identify risk factors that may lead to early introduction of effective preventive measures.

4. The most common cancers in
Developed Countries: Breast, Prostate, Lung, Colon/rectum
Developing Countries: Lung, Stomach & Liver in men and Breast, Cervix & Lung in women
About 1/3 of all cancers worldwide are attributed to the following modifiable life style factors:
Tobacco use, low fiber diet, air pollutes, contaminated injections, alcohol consumption, physical inactivity, unprotected sex & indoor household smoke.

5. Cancer Incidence Men Women Children 1 Prostate Breast Leukemia 2 Lung
Gliomas 3
Colorectal
Bone Sarcoma 4
Urinary Bladder
Endometrium
Endocrine 5
Lymphoma
Soft Tissue sarcoma ? ?

6. Cancer Incidence
Why??
Death Rate in women as a result of Cervical Cancer has
Death Rate in men as a result of Lung Cancer has
The declining death rate from cervical cancer is directly related to (1) widespread use of cytological smear studies for early detection of the tumour and its precursor lesions and to (2) The development of human papilloma virus (HPV) vaccine may eliminate this cancer in the coming years.
Due to screening tests of early cancer detection using cervical smear examination
Extended Modular Program

7. Cancer Incidence Why?? Why??
Striking climb in rate of lung cancer in women
Death Rate as a result of Cancer Stomach has
The rise in cancer lung in women most probably due to increase smoking among women these days. While the decline in death rate for cancer stomach are obscure (?) however there have speculations about decreasing exposure to dietary carcinogens.

8. Epidemiologic Factors
The role of some factors in the causation of cancer:
well established
still observational studies
unknown.
The pattern and incidence of cancer depends upon:
Predisposing Epidemiologic Factors
Pre-malignant (Chronic Non-neoplastic) Factors
Role of Hormones in Cancer

9. Predisposing Epidemiologic Factors:
Familial & Genetic Factors
Racial & Geographic Factors
Environmental & Cultural Factors
Age
Sex

10. A. Predisposing Factors
Cancers with familial occurrence:
colon, breast, ovary, brain and melanoma.

11. A. Predisposing Factors
1. Familial (Hereditary) & Genetic Factors:
Hereditary forms of cancer are divided into 3 main categories based on their pattern of inheritance as:
(a) autosomal dominant,
(b) autosomal recessive &
(c) uncertain pattern of inheritance

12. Autosomal Dominant Cancer Syndromes
They include well defined cancers in which inheritance of a single mutant gene greatly increase the risk of developing a tumour.
Retinoblastoma:
40% are familial & sporadic cases 60%.
Inherited mutation in a tumour suppressor gene called retinoblastoma gene (RB gene).

13. Not for Studying Now

14. Retinoblastoma “Familial” Arising from: neuronal cell in the retina.
Age: around 2 years.
Type of mutation: loss of portion of chromosome 13 where retinoblastoma gene (tumour suppressor gene) is located.
Inherited absence of a single copy of RB gene predisposes to retinoblastoma. The tumour develops when the other copy of the gene is also lost (one hit of mutation is needed)
It can develop bilaterally and osteogenic sarcoma can also occur.

15. Inherited Predisposition to Cancer
I. Inherited Autosomal Dominant Syndromes
Retinoblastoma (40%): RB tumour suppressor gene
Familial Adenomatous Polyposis/ Colonic Cancer: APC
Breast & Ovarian Cancer: BRCA1
Breast Cancer: BRCA2
Neurofibromatosis type I & II: NF1 & NF2
Li Fraumeni syndrome (rhabdomyosarcoma, breast, leukemia & adrenal tumours) & various tumours: P53
II. Inherited Autosomal Recessive Syndrome
Xeroderma Pigmentosum (damage by sunlight to DNA in epidermal cells resulting in multiple skin malignancies) (Children of the Night): Defective DNA Repair Gene
III. Familial Cancer with still undetected defective inherited gene
Breast (not linked to BRCA)
Colon (not linked to APC)
Ovary, brain, melanoma, & pancreatic tumours
Defect in DNA Repair Gene

16. Predisposing Epidemiologic Factors:
Familial & Genetic Factors
Racial & Geographic Factors
Environmental & Cultural Factors
Age
Sex

17. 2. Racial & Geographic Factors
Death rates from:
Liver cancer is higher in
African than American.
Breast cancer is 4-5 times greater in
United States than Japan
Stomach cancer is about 7 times more in
Japan than United States
Cancer incidence in EGYPT (Aswan):
Liver, Urinary Bladder & Lung (male)
Breast, Liver & Brain (female)
Back to Primary School

18. 3. Environmental & Cultural Factors
In your opinion which is more important environmental or hereditary factors?
Environmental factors are more important (65%) than hereditary factors (35%).
They are present in all the surroundings in:
Personal practices: smoking even the passive one & alcohol
Food: diet low in fiber & rich in fat
Universe: sunlight
Occupations exposed to: asbestos, arsenic, vinyl chloride & naphthalamine

19. Extended Modular Program
Agent
Cancer Site
Use or Occurrence
Arsenic
Lung, skin, angiosarcoma
Component of alloys, herbicides & fungicides
Asbestos
Lung, mesothelioma, colon
Cables, roofing shipyard
Benzene
Leukemia
Component of light oil
Vinyl chloride
Angiosarcoma in liver
Adhesive for plastics
Ethylene Oxide
Ripening agent for fruits & nuts
Nickel compounds
Nose, lung
Nickel plating
Radon
Lung
From decay of minerals containing uranium
Some Examples
Extended Modular Program

20. 4. Age
Most cancers occur between years but the rate declines after 75
The frequency of cancer increases with age (why??):
Accumulation of mutations.
Decline in immune competence with aging.
Cancer causes death in 10% in children ˂ 15yrs by leukemias, tumours of CNS (gliomas), bone sarcomas, soft tissue sarcomas & lymphomas

21. 5. Sex
Apart from the malignant tumours of organs specific to each sex, most tumours are generally more common in men than in women EXCEPT:
cancer of breast, thyroid, gall bladder, & hypopharynx.
Cancer breast is the commonest cancer in women throughout the whole world while cancer prostate is the commonest cancer occurring in men.
Lung cancer is the second cancer common for both sexes.

22. Predisposing Epidemiologic Factors:
Familial & Genetic Factors
Racial & Geographic Factors
Environmental & Cultural Factors
Age
Sex

23. Epidemiologic Factors
The role of some factors in causation of cancer is established while that of other factors are still epidemiological and many others are still unknown.
The pattern and incidence of cancer depends upon the following:
Predisposing Epidemiologic Factors
Pre-malignant (Chronic Non-neoplastic ) Factors
Role of Hormones in Cancer

24. B. Chronic Non-neoplastic & Neoplastic (Premalignant) Conditions
These are a group of conditions or lesions that can
predispose to development of cancer.
They arise as a result of:
chronic tissue injury or inflammation
It is important to recognize these lesions early:
to prevent cancer development
Why?

25. B. Chronic Non-neoplastic & Neoplastic (Premalignant) Conditions
Barrette's esophagus (??)
(columnar metaplasia) in gastro-esophageal reflux may lead to adenocarcinoma
Chronic gastritis & helicobacter gastritis with (??)
intestinal metaplasia can lead to carcinoma or lymphoma
Adenoma of the colon is a risk of (??)
colonic adenocarcinoma
Ulcerative colitis (inflammatory bowel disease) can predispose to colonic adenocarcinoma
Liver cirrhosis (??) predisposes to hepatocellular carcinoma

26. B. Chronic Non-neoplastic & Neoplastic (Premalignant) Conditions
Squamous metaplasia, dysplasia & carcinoma in situ in bronchi of smokers is a risk of(??)
Leukoplakia (white areas) (dysplasia) of the oral cavity is a risk for squamous cell carcinoma
Chronic irritation from a ragged tooth leads to squamous dysplasia
Old burn scar or chronic wound may lead to development of squamous cell carcinoma (Marjolin’s Ulcer)
Neurofibromas (benign tumours) may lead to sarcoma
Squamous cell carcinoma

27. Epidemiologic Factors
The role of some factors in causation of cancer is established while that of other factors are still epidemiological and many others are still unknown.
The pattern and incidence of cancer depends upon the following:
Predisposing Epidemiologic Factors
Chronic Non-neoplastic (Pre-malignant) Factors
Role of Hormones in Cancer

28. C. Role of Hormones Unopposed estrogenic stimulation leads to:
endometrial hyperplasia with atypia leads to increased risk of endometrial adenocarcinoma
Contraceptive hormones maybe related to:
breast cancer and benign liver cell adenoma
Anabolic steroids used by athletes increase the risk of development of:
benign & malignant liver tumours

29. To Summarize Epidemiologic Predisposing Factors Epidemiology Cancer
Familial Cancers: autosomal dominant, autosomal recessive & unknown
Racial or Geographic Factors: liver cancer, breast cancer, stomach cancer
Environmental Factors: smoking, occupation related, universe & food
Age: old (why?)
Sex: male more than female
To Summarize
Epidemiology Cancer
Premalignant Lesions:
Squamous metaplasia
Leukoplakia
Barrette esophagus
Chronic Gastritis
Colonic adenoma
Ulcerative colitis
Liver cirrhosis NF
Ragged tooth
Marjolin Ulcer
Role of Hormone:
Unopposed Estrogen
Contraceptive hormones
Anabolic steroids

30. What are the carcinogenic agents you know?
Chemical Carcinogens
Physical Carcinogens
Biological Carcinogens

31. Chemical Carcinogenesis
It occurs after years, varies according to dose & mode of administration, individual susceptibility & predisposing factors.
It occurs by induction of mutation in the proto-oncogenes & anti-oncogenes.
The process involve 3 sequential (successive) stages: initiation, promotion & progression.

32. Radiation Carcinogenesis
Mechanism of action of radiation:
Chromosome breakage
Translocations
Point mutations (less frequent)
Radiation is an established carcinogen (as UV rays, X-rays, nuclear fission, mines of radioactive substances):
Skin cancers (melanoma, squamous cell and basal cell carcinomas)
Papillary thyroid carcinoma (irradiation of the head and neck) 
Lung cancers
Leukemia

33. Biological Carcinogenesis
Oncogenic Viruses:
RNA Oncogenic Viruses (HTLV-1 & HCV):
Human T cell Leukemia Virus type 1 (HTLV-1):
Can induce T cell leukemia/lymphoma
Hepatitis C Virus:
can cause hepatocellular carcinoma

34. Biological Carcinogenesis
Oncogenic Viruses:
B. DNA Oncogenic Viruses (HPV, EBV, HHV-8 & HBV):
Human Papilloma Virus (HPV) is associated with benign warts & cervical cancer
Herpes Viruses (Epstein Barr Virus) (Burkitt Lymphoma & Hodgkin Lymphoma
Human Herpes Virus 8: HHV-8 can cause Kaposi sarcoma (malignant neoplasm of blood vessels in AIDs infected persons)
Hepatitis B Virus can cause hepatocellular carcinoma

35. Biological Carcinogenesis
Oncogenic Bacteria:
Helicobacter pylori bacilli:
can produce Low grade malignant lymphoma & adenocarcinoma of the stomach
Oncogenic Parasites:
Schistosoma Hematobium can produce squamous cell carcinoma in urinary bladder on top of squamous metaplasia and transitional cell carcinoma
Oncogenic Fungi:
Asperigillus falvus liberates aflatoxin and is related to hepatocellular carcinoma

36. What is the importance of knowing the causative carcinogens?
Diagnosis: by correlating the symptoms & signs with aetiologic factor (s)
Treatment: Expect the type of cancer if the carcinogen is well known
Preventive measures & follow up

37. Complete the following sentences:
Quiz
Complete the following sentences:
The cervical cancer in women has declined due to ………………& ……………………
Patients with familial retinoblastoma can develop …………… …………… and are at increased risk of developing …………………as a second cancer.
Regarding the racial & geographic distribution, liver cancer is more prevalent in …………… population than…………. while breast cancer is present more in ………..and cancer stomach is more in………………………
In Xeroderma pigmentosum is an example of………… …………. inherited disease there is a defect in …………… gene

38. Complete the following sentences:
Quiz
Complete the following sentences:
Contraceptive pills may predispose to …………………
Anabolic steroids may lead to …………
The most common cancers in men are ………….. & ………..while in women are …………….. & ……………….
Benign tumours that may predispose to cancer are ………………….. & ……………………………..
Some long standing inflammatory & hyperplastic conditions that may predispose to cancer include ………………… of colon, …………….in skin,……………..of liver, ………………..of stomach, ……………….of esophagus, ………………of oral mucosa