Page 222 - Textbook of Pathology, 6th Edition

206 Carriers of such genetic composition have 10,000 times higher iv) South-East Asians, especially of Chinese origin develop
risk of developing retinoblastoma which is often bilateral. nasopharyngeal cancer more commonly.
Such patients are predisposed to develop another primary v) Indians of both sexes have higher incidence of carcinoma
malignant tumour, notably osteogenic sarcoma. of the oral cavity and upper aerodigestive tract, while in
Familial form of retinoblastoma is due to missing of a females carcinoma of uterine cervix and of the breast run
portion of chromosome 13 where RB gene is normally located. parallel in incidence. Cancer of the liver in India is more often
This results in a genetic defect of absence of RB gene, the due to viral hepatitis (HBV and HCV) and subsequent
first ever tumour suppressor gene identified. An absent RB cirrhosis, while in western populations it is more often due
gene predisposes an individual to retinoblastoma but cancer to alcoholic cirrhosis.
SECTION I
develops when other copy of RB gene from the other parent
is also defective. 3. ENVIRONMENTAL AND CULTURAL FACTORS.
ii) Familial polyposis coli. This condition has autosomal Surprising as it may seem, we are surrounded by an
dominant inheritance. The polypoid adenomas may be seen environment of carcinogens which we eat, drink, inhale and
at birth or in early age. By the age of 50 years, almost 100% touch. Some of the examples are given below:
cases of familial polyposis coli develop cancer of the colon. i) Cigarette smoking is the single most important environ-
iii) Multiple endocrine neoplasia (MEN). A combination of mental factor implicated in the etiology of cancer of the oral
adenomas of pituitary, parathyroid and pancreatic islets cavity, pharynx, larynx, oesophagus, lungs, pancreas and
(MEN-I) or syndrome of medullary carcinoma thyroid, urinary bladder.
pheochromocytoma and parathyroid tumour (MEN-II) are ii) Alcohol abuse predisposes to the development of cancer
encountered in families. of oropharynx, larynx, oesophagus and liver.
iv) Neurofibromatosis or von Recklinghausen’s disease. iii) Alcohol and tobacco together further accentuate the risk
This condition is characterised by multiple neurofibromas of developing cancer of the upper aerodigestive tract.
and pigmented skin spots (cafe au lait spots). These patients iv) Cancer of the cervix is linked to a number of factors such
have family history consistent with autosomal dominant as age at first coitus, frequency of coitus, multiplicity of
inheritance in 50% of patients. partners, parity etc. Sexual partners of circumcised males
v) Cancer of the breast. Female relatives of breast cancer have lower incidence of cervical cancer than the partners of
patients have 2 to 6 times higher risk of developing breast uncircumcised males.
cancer. Inherited breast cancer comprises about 5-10% of all v) Penile cancer is rare in the Jews and Muslims as they are
breast cancers. As discussed later, there are two breast cancer customarily circumcised. Carcinogenic component of
General Pathology and Basic Techniques
susceptibility genes, BRCA-1 and BRCA-2. Mutations in these smegma appears to play a role in the etiology of penile cancer.
genes appear in about 3% cases and these patients have about vi) Betel nut cancer of the cheek and tongue is quite common
85% risk of development of breast cancer.
in some parts of India due to habitual practice of keeping
vi) DNA-chromosomal instability syndromes. These are a the bolus of paan in a particular place in mouth for a long
group of pre-neoplastic conditions having defect in DNA time.
repair mechanism. A classical example is xeroderma vii) A large number of industrial and environmental
pigmentosum, an autosomal recessive disorder, substances are carcinogenic and are occupational hazard for
characterised by extreme sensitivity to ultraviolet radiation. some populations. These include exposure to substances like
The patients may develop various types of skin cancers such arsenic, asbestos, benzene, vinyl chloride, naphthylamine etc.
as basal cell carcinoma, squamous cell carcinoma and
malignant melanoma. viii) Certain constituents of diet have also been implicated
in the causation of cancer. Overweight individuals, deficiency
2. RACIAL AND GEOGRAPHIC FACTORS. Differences of vitamin A and people consuming diet rich in animal fats
in racial incidence of some cancers may be partly attributed and low in fibre content are more at risk of developing certain
to the role of genetic composition but are largely due to cancers such as colonic cancer. Diet rich in vitamin E, on the
influence of the environment and geographic differences other hand, possibly has some protective influence by its
affecting the whole population such as climate, soil, water, antioxidant action.
diet, habits, customs etc. Some of the examples of racial and
geographic variations in various cancers are as under: 4. AGE. The most significant risk factor for cancer is age.
Generally, cancers occur in older individuals past 5th decade
i) White Europeans and Americans develop most of life (two-third of all cancers occur above 65 years of age),
commonly malignancies of the lung, breast, and colon. Liver though there are variations in age incidence in different forms
cancer is uncommon in these races. Breast cancer is of cancers. It is not clear whether higher incidence of cancer
uncommon in Japanese women but is more common in in advanced age is due to alteration in the cells of the host,
American women.
longer exposure to the effect of carcinogen, or decreased
ii) Black Africans, on the other hand, have more commonly ability of the host immune response. Some tumours have
cancers of the skin, penis, cervix and liver. two peaks of incidence e.g. acute leukaemias occur in children
iii) Japanese have five times higher incidence of carcinoma and in older age group. The biologic behaviour of tumours
of the stomach than the Americans. in children does not always correlate with histologic features.