Epidemiology Of Cancer Notes

Epidemiology Of Cancer

It is widely known that no single etiologic factor is responsible for the development of tumours. While the role of some etiologic factors in neoplasms is known, many factors are established by epidemiological studies while others are still unknown.

Then, there are certain diseases which have a predisposition to develop cancers. Endogenous or exogenous excess of hormones in predisposing some cancers is also known.

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Thus, the subject of epidemiology here is discussed under the following headings:

• Cancer incidence
• Predisposing factors
• Acquired predisposing diseases
• Predisposing hormones

Cancer Incidence

The overall incidence of cancer in a population or a country is known by the registration of all cancer cases (cancer registry) and by rate of death from cancer. Worldwide, it is estimated that about 20% of all deaths are cancer-related; in US, cancer is the second most common cause of deaths, next to heart disease.

There have been changing patterns in the incidence of cancers in both sexes and in different geographic locations as outlined below. Shows worldwide incidence (in descending order) of five most common cancers in men, women, and children.

Due to varying etiologic factors, cancers of the uterine cervix in females and oral cavity in males are more common in India while cancers of the breast in women and lung in men are commoner in the Western populations.

Worldwide, the most common cancers in developed and developing countries are as under:

• Developed countries Lung, breast, prostate and colorectal.
• Developing countries’ Liver, cervix, oral cavity and oesophagus.

Strategies for cancer prevention and control require not only education for the avoidance of carcinogens implicated in various cancers but also to identify people at risk and by having effective screening programmes for early detection of common cancers.

• About one-third of all cancers worldwide are attributed to following modifiable risk factors requiring public health education:
  • Smoking cessation
  • Diet modification (low-fat and high-fibre diet)
  • Physical activity
  • Energy balance by caloric restriction to avoid obesity, and
  • Avoidance of excessive sun-exposure.
• Overall, there has been a declining trend in incidence of some of the cancers by early detection due to effective periodic screening programmes in many developed countries for example,
  • Cancers of the cervix (by Pap screening)
  • Breast (by screening mammography)
  • colorectal region (by surveillance colonoscopy)
  • Prostate (screening by serum PSA), and
  • Liver (screening by serum AFP).

Predisposing Factors

Epidemiological studies give an insight into the prevalence of cancers and the identification of possible predisposing factors in different populations.

These are:

1. Constitutional factors (age and gender)
2. Familial and
3. Genetic factors
4. Racial and geographic factors
5. Environmental and cultural factors.

Five most common primary cancers in the world:

1. Constitutional Factors:

Age and gender are important constitutional risk factors for different cancers.

• Age:  The most significant risk factor for cancer is age. Cancers occur more frequently in older individuals past 5th decade of life (two-thirds of all cancers occur above 65 years of age), though there are variations in age incidence in different forms of cancers.
  • A higher incidence of cancer in advanced age could be due to alteration in the cells of the host, longer exposure to the effect of carcinogen, or decreased ability of the host immune response.
  • Some tumours have two peaks of incidence for example, Acute leukaemias occur in children and in older age groups.
  • The biological behaviour of tumours in children does not always correlate with histologic features.
  • Besides acute leukaemias, other common tumours in infancy and childhood are:
  • CNS tumours, neuroblastoma, nephroblastoma (Wilms’ tumour), retinoblastoma, hepatoblastoma, rhabdomyosarcoma, Ewing’s sarcoma and teratoma.
• Gender: Apart from the malignant tumours of organs peculiar to each sex, most tumours are generally more common in men than in women except for cancer of the breast, gallbladder, thyroid and hypopharynx.
  • Although there are geographic and racial variations, cancer of the breast is the commonest cancer in women throughout the world while lung cancer is the commonest cancer in men.
  • The differences in the incidence of certain cancers in the two sexes may be related to the presence of specific sex hormones.

2. Familial And Genetic Factors:

It has long been suspected that familial predisposition and heredity play a role in the development of cancers. In general, the risk of developing cancer in relatives of a known cancer patient is almost three times higher as compared to control subjects. Some of the cancers with familial occurrence are of the colon, breast, ovary, brain and melanoma.

Familial cancers occur at a relatively early age, may appear at multiple sites and occur in 2 or more first-degree blood relatives. The overall estimates suggest that genetic cancers comprise about 5% of all cancers. Some of the common examples are as under:

• Retinoblastoma: About 40% of retinoblastomas are familial and show an autosomal dominant inheritance. Carriers of such genetic composition have a 10,000 times higher risk of developing retinoblastoma which is often bilateral.
  • The familial form of retinoblastoma is due to the missing of portion of chromosome 13 where RB gene is normally located.
    In fact, the genetic absence of the RB gene was the first ever tumour-suppressor gene identified.
  • The absence of a single copy of the RB gene predisposes an individual to retinoblastoma and the tumour develops when another copy of the RB gene from the second parent is also defective.
  • Such patients are further predisposed to develop another primary malignant tumour, notably osteogenic sarcoma.
• Adenomatous polyposis coli (APC):  This condition has autosomal dominant inheritance. Multiple polypoid adenomas may be seen at birth or an early age. By the age of 50 years, almost 100% of cases of APC develop cancer of the colon.
• Multiple endocrine neoplasias (MEN):  A combination of adenomas of pituitary, parathyroid and pancreatic islets (MEN-I) or syndrome of medullary carcinoma thyroid, pheochromocytoma and parathyroid tumour (MEN-II) are encountered in families.
• Neurofibromatosis or von Recklinghausen’s disease: This condition is characterised by multiple neurofibromas and pigmented skin spots (cafe aü lait spots). These patients have a family history consistent with autosomal dominant inheritance in 50% of patients.
• Cancer of the breast: Female relatives of patients with breast cancer have 2–6 times higher risk of developing breast cancer. Inherited breast cancer comprises about 5-10% of all breast cancers.
  • As discussed later, there are two breast cancer susceptibility genes, BRCA-1 and BRCA-2.
  • Mutations in these genes appear in about 3% of cases and these patients have about 85% risk of development of breast cancer.
• Congenital chromosomal syndromes For example:
  • Down’s syndrome or mongolism has trisomy 21; these cases have increased risk of development of acute leukaemia.
  • Klinefelter syndrome is associated with an extra X chromosome (47, XXY); these cases have a high risk of developing cancer of the male breast and extra-gonadal germ cell tumours.
• DNA-chromosomal instability syndromes: These are a group of pre-neoplastic conditions having defects in the DNA repair mechanism.
  • A classical example is xeroderma pigmentosum, an autosomal recessive disorder, characterised by extreme sensitivity to ultraviolet radiation.
  • The patients may develop various types of skin cancers such as basal cell carcinoma, squamous cell carcinoma and malignant melanoma.
• Li-Fraumeni syndrome: In this syndrome, there is an inherited predisposition to develop cancers at multiple primary sites and they occur at a younger age.
  • The most common sites are cancer breast, sarcomas, brain tumours, leukaemias and adrenal cortical tumours.
  • Li-Fraumeni tumours occur in individuals due to two hits: an inherited mutant TP53 allele and an additional acquired mutation of the TP53 allele.
  • Person carrying this inherited mutation have about 25 times higher risk of developing cancer by the age of 50 than the general population.

3. Racial And Geographic Factors:

Differences in racial incidence of some cancers may be partly attributed to the role of genetic composition but are largely due to the influence of the environment and geographic differences affecting the whole population such as climate, soil, water, diet, habits, customs etc.

Some of the examples of racial and geographic variations in various cancers are as under:

• White Europeans and Americans: More common cancers of the lung, breast and colorectal region. Liver cancer has lower incidence in these races.
• Blacks: More common cancers of the lung, liver, prostate and penis and cervix.
• Japanese: They have a five times higher incidence of carcinoma of the stomach than the Americans. Breast cancer is more uncommon in Japanese women than American women.
• South-East Asians: Higher incidence of nasopharyngeal cancer.
• Indians: Higher incidence of carcinoma of the oral cavity and upper aerodigestive tract in both sexes, while in females carcinoma of the uterine cervix and of the breast run parallel in incidence.

The etiologic factor responsible for liver cancer in India is more often viral hepatitis (HBV and HCV) and subsequent cirrhosis, while in western populations it is more often due to alcoholic cirrhosis.

4. Environmental And Cultural Factors:

It may seem rather surprising that throughout life, we are surrounded by an environment of carcinogens which we eat, drink, inhale and touch.

Some of the examples are given below:

• Cigarette smoking:  (as well as passive inhalation) Is the single most important environmental factor implicated in the etiology of many cancers:
  • Lung
  • Oral cavity
  • Pharynx
  • Larynx
  • Nasal cavity and
  • Paranasal sinuses
  • Oesophagus
  • Stomach
  • Pancreas
  • Liver
  • Kidney
  • Urinary bladder
  • Uterine cervix and Myeloid leukaemia.
• Alcohol abuse: Predisposes to the development of cancer of the oropharynx, larynx, oesophagus and liver.
• Synergistic interaction:  Synergistic interaction: Of alcohol and tobacco further accentuates the risk of developing cancer of the upper aerodigestive tract and lung.
• Cancer of the cervix: Cancer of the cervix Is linked to a number of factors such as age at first coitus, frequency of coitus, multiplicity of partners, parity etc. Sexual partners of circumcised males have lower incidence of cervical cancer than the partners of uncircumcised males.
• Penile cancer: Penile cancer Is rare in the Jews and Muslims as they are customarily circumcised. The carcinogenic component of smegma appears to play a role in the etiology of penile cancer.
• Betel-nut cancer: Betel-nut cancer  Of the cheek and tongue is quite common in some parts of India due to habitual practice of keeping the bolus of pain at one location in the mouth for a prolonged duration.
• Industrial and environmental substances: In many occupations are carcinogenic and are occupational hazards for workers and their families. These include exposure to substances like arsenic, asbestos, benzene, vinyl chloride, naphthylamine etc.
• Certain constituents of diet: Have also been implicated in the causation of cancer. Overweight individuals, those consuming high-fat and low-fibre diets, and diet deficient in vitamin A, are more at risk of developing certain cancers such as colorectal cancer.
• A diet rich in vitamin E, on the other hand, possibly has some protective influence by its antioxidant action.