Tishk International University

Science Faculty

Medical Analysis Department

Pathology

Fourth Grade- Spring Semester 2020-2021

Dr. Jalal A. Jalal Assistant Professor of

Pathology

Neoplasia- 3, Epidemiology

of Cancer

EPIDEMIOLOGY

Cancer Incidence:

2

1. Geographic and Environmental Variables

3

Occupational Cancers

• Arsenic : Lung, skin, Angiosarcoma.

• Asbestos: Lung, mesothelioma;

• Benzene: Leukemia, Hodgkin lymphoma.

• Beryllium: Lung

• Cadmium: Prostate

• Chromium: Lung

• Ethylene oxide: Leukemia

• Nickel: Nose, lung

• Radon: Lung

• Vinyl chloride: Angiosarcoma, liver

4

2. Age

• In general, the frequency of cancer increases with

age.

• Most cancer mortality occurs between ages 55

and 75 years.

• Cancer causes about 10% of all deaths among

children younger than 15 years.

• The major lethal cancers in children are

leukemia,

tumors of the central nervous system,

lymphomas,

soft tissue sarcomas, and

bone sarcomas.5

3. Heredity

• Evidence now indicates that for many types ofcancer, there exist not only environmentalinfluences but also hereditary predispositions.

• In summary, about 5% to 10% of all human

cancers are categorized under hereditary forms

of cancer.

6

4. Acquired Preneoplastic Disorders

certain clinical conditions are well-recognizedpredispositions to the development of malignantneoplasia and are referred to as preneoplasticdisorders.1. Chronic skin fistula or a longstanding-unhealedskin wound may lead to Squamous cell carcinoma.2. Cirrhosis of the liver may lead to Hepatocellular

carcinoma.3. Atypical endometrial hyperplasia; may lead toEndometrial carcinoma.4. Dysplastic bronchial mucosa of habitual cigarettesmokers may lead to Bronchogenic carcinoma.

7

5. Chronic atrophic gastritis e.g., gastric carcinoma

in pernicious anemia or following long-standing

Helicobacter pylori infection.

6. Chronic ulcerative colitis (e.g., an increased

incidence of colorectal carcinoma in long-standing

disease).

7. Leukoplakia of the oral cavity (e.g., increased risk

of squamous cell carcinoma).

8. Villous adenomas of the colon (e.g., high risk of

transformation to colorectal carcinoma).

8

CARCINOGENESIS:

THE MOLECULAR BASIS OF CANCER

• Nonlethal genetic damage lies at the heart ofcarcinogenesis.

• Such genetic damage (or mutation) may beacquired by the action of environmental agents,such as chemicals, radiation, or viruses, or it maybe inherited in the germ line.

• The genetic hypothesis of cancer implies that atumor mass results from the clonal expansion ofa single progenitor cell that has incurred geneticdamage (i.e., tumors are monoclonal).

9

Four classes of normal regulatory genes are the

principal targets of genetic damage:

1. Growth-promoting proto-oncogenes,

2. Growth-inhibiting tumor suppressor genes,

3. Genes that regulate programmed cell death-

apoptosis

4. Genes involved in DNA repair.

10

• Mutant alleles of proto-oncogenes are called

oncogenes.

• They are considered dominant because

mutation of a single allele can lead to cellular

transformation.

• In contrast, typically both normal alleles of

tumor suppressor genes must be damaged for

transformation to occur, so this family of genes

is sometimes referred to as recessive

oncogenes.

• Genes that regulate apoptosis may be dominant,

as are proto-oncogenes, or they may behave as

tumor suppressor genes.

• DNA repair genes affect cell proliferation or

survival indirectly by influencing the ability of the

organism to repair nonlethal damage in other

genes, including proto-oncogenes, tumor

suppressor genes, and genes that regulate

apoptosis.

•

12

• A disability in the DNA repair genes can

predispose cells to widespread mutations in the

genome and thus to neoplastic transformation.

• Carcinogenesis is a multistep process at both

the phenotypic and the genetic levels, resulting

from the accumulation of multiple mutations.

• malignant neoplasms have several phenotypic

attributes, such as excessive growth, local

invasiveness, and the ability to metastases.

• It is well established that over a period of time,many tumors become more aggressive andacquire greater malignant potential.

• This phenomenon is referred to as tumorprogression.

• Even though most malignant tumors aremonoclonal in origin, by the time they becomeclinically evident, their constituent cells areextremely heterogeneous.

14

• tumor progression and associatedheterogeneity most likely result from multiplemutations that accumulate independently indifferent cells, generating subclones withdifferent characteristics.

16

17

30