EPIDEMIOLOGY

OF
CANCER
 OVERVIEW
1. Incidence & Distribution of Cancer
2. Factors affecting the incidence
3. Various acquired and genetic premalignant
conditions and their interactions
4. Inherited cancer syndromes and how they
are inherited.
INCIDENCE & DISTRIBUTION OF
CANCER IN HUMANS
Incidence & Mortality Rates
 Cancer is the second overall leading cause of
death (after ischemic heart disease) in the world.
The incidence continues to rise, probably
reflecting the increasing average age of the
population.
Major Factors Affecting Incidence
 The presence or absence of any of the many
factors influencing the incidence of cancer must
be established during history taking and
physical examination of a patient thought to
have cancer.
 In 2008 :
 12.7 million new cases
 7.6 million deaths (21000/day)

By 2030 :
 21.4 million new cases
 13.2 million deaths (<36000/day)
Cancer incidence
Two-thirds of cancer occurs in 5 sites (for each sex)
Rates vary geographically and with time

Because of different survival rates, these incidence figures do not

correspond to cancer deaths by site

Females (%) Males (%)

 Breast 26  Prostate 25
 Lung 14  Lung 15
 Colorectal 10  Colorectum 10
 Endometrium 9  Leuk/lymphoma 8
 Leuk/lymphoma 8  Bladder 7
Cancer incidence

Other prominent sites:

- Cervix
- Ovary
- Stomach
- Esophagus
- Pancreas
- Kidney
- Skin
Cancer incidence—secular changes
Age adjusted cancer death rates have
decreased due to:
1- Preventive measures :
.Smoking;mouth,pharynx,larynx,esophagus
.Alcohol;oropharynx,larynx,esophagus,liver
2- Improved diagnostic and treatment modalities
Decreasing
 Stomach
 Endometrium
 Liver
 Colorectal (females)
INCIDENCE & DISTRIBUTION OF
CANCER IN HUMANS..

Major Factors Affecting Incidence

 The presence or absence of any of the
many factors influencing the incidence of
cancer must be established during history
taking and physical examination of a
patient thought to have cancer.
 Sex:
Frequency in Developed countries:
 Men- Prostate, Lung, Colon
(Lung, Stomach, Liver)
 Women- Breast, Lung, Colon
(Breast, Cervix, Lung)
 Age:
 Female: 40-79 years.
Male: 60-79 years.
 Accumulation of somatic mutations.
 Decline in immune competence.
 Adults- Carcinomas
Children- Leukemias, CNS tumors, Small
round blue cell tumors
(Neuroblastoma, Retinoblastoma, Wilm’s tumor,
Rhabdomyosarcoma)
 Acquired predisposing conditions:
 - Chronic inflammations
.Asbestosis
.Silicosis
.Bronchitis
.Osteomyelitis
.Cystitis
.Gastritis
.Pancreatitis
 - Precursor lesions
.Metaplasia
.Hyperplasia
.Dysplasia
Biologic and Clinical Effects of Neoplasms
Acquired predisposing conditions…..:
- Immunodeficiency states
. T cell immunity disorders
. Viral induced: HIV/ AIDS
. Mainly B cell Lymphomas
. Carcinomas, Sarcomas
 Occupational, Social, and Geographic Factors:
 Occupational factors have been mentioned with
reference to an increased risk of bladder cancer in
workers in the ‘dye industry’ and lung cancer in certain
‘miners’.
 Because the risk is so high in certain industries, an
occupational history is an essential part of a full
medical examination.
 Similarly, such social habits as ‘cigarette smoking’
represent risk factors for development of several types
of cancer, and the physician must evaluate the amount
of exposure to these factors during history taking.
 Infectious agents:
- 15 % of all the cancers
- Higher in developing countries
- HPV; STD: CA Cervix, Head/neck tumors
- Helicobacter pylori: CA stomach
- EBV: Lymphomas
 Childbearing; cumulative estrogen stimulation
 Socioeconomic status
 Geographic area or country
 Eating and drinking habbits; grilled meat, high fat
diet, alcohol
 UV rays , Smog

are the other factors affecting the development of

specific types of cancer
 Family History:

 A few cancers have a simple pattern of genetic

inheritance and those that do are so striking that
they warrant careful study of relatives of known
cases
 (eg, retinoblastoma, polyposis coli and
carcinoma of the colon, medullary carcinoma of
the thyroid, hereditary breast-ovary carcinoma
syndromes).
 Inherited cancer syndromes
 Li-Fraumeni syndrome - p53;
breast, bladder, sarcoma

 Familial retinoblastoma – Rb;

- autosomal dominant
- inherit one defective copy of Rb gene in the germline
(first hit)
- spontaneous somatic mutation in the retinoblasts
(second hit)
- unilateral/bilateral retinoblastoma
 Inherited cancer syndromes…
 Xeroderma pigmentosum – XPAC;
- Inherited autosomal recessive disorder
- Defects in DNA repair
- Skin cancer; exposure to UV light cross linking of
pyrimidine residues preventing normal DNA
replication/repair

 Hereditary Breast-Ovary Cancer (HBOC)-

BRCA1, BRCA2
 Genetic Oncogenesis
(The Role of Inheritance in Oncogenesis)
1. Neoplasms With Mendelian (Single-Gene)
Inheritance
 Retinoblastoma. This uncommon malignant neoplasm of the
retina occurs in children, and 10% of cases are inherited. The
morphologic appearance of familial retinoblastoma is the same as
that of the non-inherited form. Familial form displays other
distinguishing features:
 (1) it is commonly bilateral;
 (2) chromosomal analysis consistently shows an abnormality of
the long arm of chromosome 13 (13q14, the retinoblastoma
[Rb1] gene);
 (3) spontaneous regression occurs in some cases.
 Wilms' tumor (nephroblastoma)
 Nephroblastoma is a malignant neoplasm of
the kidney that occurs mainly in children.
 Many cases are associated with deletion of
part of chromosome 11. Both sporadic and
familial cases occur by mechanisms thought
to resemble those described for
retinoblastoma.
 11p13 abnormalities are being identified in
other tumor types.
 WT-1 is also a tumor suppressor gene.
Several other neoplasms display a familial pattern.
 Neurofibromatosis (type 1 von Recklinghausen's disease)- This
tumor is characterized by multiple neurofibromas and pigmented
skin patches known as café au lait spots. In neurofibromatosis, the
NF-1 genes (chromosome 17q11) are absent or defective, leading
to loss of NF-1 suppressor protein. NF-1 protein is thought to act
by regulating the effect of the products (guanine-binding G
proteins) of the ras proto-oncogene.
 Multiple endocrine neoplasia- This disorder is manifested by
benign neoplasms in the thyroid, parathyroid, pituitary, and
adrenal medulla.
 Familial polyposis coli- Polyposis coli is characterized by
innumerable adenomatous polyps in the colon. (There is loss of
heterozygosity on the long arm of chromosome 5, the APC-
adenomatous polyposis coli-gene).
 Gardner's syndrome
 Turcot's syndrome,
 2. Neoplasms With Polygenic
Inheritance:
 Many common human neoplasms are familial to a
much lesser degree- ie, they occur in related
individuals more often than would be expected on
the basis of chance alone.
 Breast cancer. First degree female relatives
(mother, sisters, daughters) of pre-menopausal
women with breast cancer have a risk of
developing breast cancer that is five times higher
than that of the general population.
 Colon cancer.
3. Neoplasms Occurring More Frequently in
Inherited Disease:
 (a) syndromes characterized by increased
chromosomal fragility
(eg, Xeroderma pigmentosum, Bloom's syndrome,
Fanconi's syndrome, and ataxia-telangiectasia), in
which neoplasia is due to frequent DNA
abnormalities; and
 (b) syndromes of immunodeficiency,
in which failure of immune surveillance may
predispose to neoplasia. In these disorders, it is not
the neoplasm itself that is inherited but rather some
susceptibility to neoplasia.
 Summary
 Incidence of cancer varies with geography, age, race and genetic
background.
 Environmental factors of significance are infectious agents,
smoking, alcohol, diet, obesity, reproductive history and
carcinogens.
 Reparative proliferations caused by chronic inflammations, tissue
injury, hyperplasia/ metaplasia also increases risk of developing
cancer.
 Interaction between genetic and environmental factors is
determinant of cancer risk.
MCQ’s
 1- An 8 year old boy is referred to a dermatologist for
suspicious looking pigmented lesion with irregular
margins on the face. Histopathology report confirmed the
diagnosis of malignant melanoma. Based on other
investigations diagnosis of Xeroderma pigmentosum is
considered. This condition results from:
 a. Aberrant expression of receptor tyrosine kinase
 b. An inborn defect in DNA repair
 c. Chemical carcinogen
 d. DNA viral infection
 e. Retroviral infection
MCQ’s..Answer
 a. Aberrant expression of receptor tyrosine kinase
 b. An inborn defect in DNA repair
 c. Chemical carcinogen
 d. DNA viral infection
 e. Retroviral infection
MCQ’s….
 2- A 76 years old farmer presents with a 2 cm mass on the
left side of the forehead. Biopsy reveals squamous cell
carcinoma. Which one of the following causes formation
of pyrimidine dimers in DNA and is associated with the
formation of squamous cell carcinoma?
 a. Aflatoxin B1
 b. Vinyl chloride
 c. Asbestos
 d. UV rays
 e. Epstein-Barr virus
MCQ’s…Answer
 a. Aflatoxin B1
 b. Vinyl chloride
 c. Asbestos
 d. UV rays
 e. Epstein-Barr virus
SEQ’s
 Describe various environmental factors that has an
established role as a risk factor in the development of
cancer.
 1. Infectious agents
 2. Smoking
 3. Alcohol
 4. Diet
 5. Obesity
 6. Reproductive history
 7. Environmental carcinogens
 2- Enlist environmental carcinogens and the occupational
cancers caused by them.