Cancer-A Brief in depth knowledge of the causes and cure of this silent killer
The term “cancer” is derived from Latin word “cancrum” or Greek “karkinoma”, that is equivalent to Sanskrit term “karkitakam”, which means “crab”. The disease is so called because of swollen veins around the area, resemble a crab’s limbs.
Indian Medical Science had identified cancer, gave the name “arbuda”, which literally means the number 108 , identifying the extreme cellularity of the cancer tissue.
The International Union Against Cancer (UICC; Union Internationale Contre le Cancer) has defined cancer as a disturbance of growth characterised by excessive proliferation of cells without apparent relation to the physiological demands of the organs involved.
Oncology deals with the etiology, diagnosis, treatment, prevention and research aspects of cancer.
Etiology of Cancer All cancers are multifactorial in origin. They include genetic, hormonal, metabolic, physical, chemical and environmental factors. Most human cancers are spontaneous.
All cancers originate usually from one aberrant cell, which goes on to multiply and produce a tumor mass.
One mutation occurs out of 106 cell divisions. By the time a person reaches adulthood, about 1026 cell divisions have occurred. Thanks to the surveillance by the immune system, these aberrant cells are usually destroyed.
As age advances, the number of mutations accumulate, hence the statistical probability of the incidence of cancer is increased. No wonder, cancer is a disease of old age, especially after 60 years.
Cancer is the second most common cause for death in developed countries, second only to cardiovascular diseases. When the average life expectancy is less, as in the case of India, the death due to cancer is also low.
Oral cavity and upper gastrointestinal tract are the organs where cancer occurs most often in India. On the other hand, lungs and colon are the common sites for cancer in Western countries.
Mutagens Any substance which increases the rate of mutation can also enhance the rate of incidence of cancer. Therefore all carcinogens are mutogens. Examples are X-ray, gamma-ray, ultraviolet ray. Some human cancers are caused by chemicals. These may be introduced into the body by means of (a) occupation (aniline, asbestos), (b) diet (aflatoxins) or (c) lifestyle (smoking). Chemical carcinogens act cumulatively. Tobacco, food additives, coloring agents, and aflatoxins are common carcinogens in our environment.
Thousands of chemicals are known mutagens and carcinogens.Methyl cholanthrene is a powerful carcinogen, only nanograms are sufficient to produce a tumor in a mouse .
Aflatoxins They are a group of chemically related compounds synthesised by the fungi, Aspergillus flavus. The mould grows on rice, wheat and groundnut, when kept in damp conditions. The fungi may grow in cattle fodder, which may enter into human body through the cow’s milk.
Aflatoxins are powerful carcinogens, which produce hepatomas.
Cigarette Lung cancer is associated with the habit of cigarette smoking. Cigarette contains many carcinogens, the most important group being benzo(a)pyrenes. Other important deleterious substances in cigarette smoke are nicotine, carbon monoxide, nitrogen dioxide and carbon soot.
Statistically, it is estimated that one cigarette reduces 10 minutes from the life span of the individual. The incidence of lung cancer is increased to 15 times more in persons smoking 10 cigarettes per day and 40 times more when smoking 20 cigarettes per day.
Thus WHO suggested the slogan ‘cigarette smoke is injurious to health’. Moreover, non-smoking spouse of a heavy smoker will have 5 times more probability to get lung cancer than a non-smoker.
This effect of ‘passive smoking’ made the International Union against Cancer (UICC) to change the slogan to ‘Your smoking is injurious to our health’. Oral cancer is strongly associated with chewing of tobacco. Oral cancer constitutes 20% of all cancers seen in India, whereas it is less than 1% in Western countries.
Alcohol intake increases the risk of oral, pharyngeal, esophageal and liver cancers. Diet high in total fat and cholesterol, increases the risk of colon, breast and prostate cancers.
An often asked question is, why only some smokers are getting cancer and not all smokers? Glutathione-Stransferase (GST) is involved in the detoxification of various carcinogens, including cigarette smoke.
About 5% of population are lacking in GST. Smokers who are devoid of GST are more prone to develop lung cancer. There are 3 different genes and 3 iso-enzymes for GST. Promoters of Cancer Most carcinogens require promoters for the production of a cancer. Benzopyrene applied on skin does not produce cancer. Croton oil application also does not lead to skin cancer.
But when benzopyrene application is followed by croton oil, tumor is developed. In this case, croton oil is termed as the promoter. The active agent in croton oil is a phorbol ester, tetradecanoyl phorbol acetate (TPA). It activates Protein kinase-C.
This results in phosphorylation of membrane proteins, leading to the triggering of malignancy. The carcinogen produces a mutation, but the promoter gives the drive for unchecked cell division. Progression The biological history of a tumor shows progression of malignancy.
Cells with faster growth rate have a selection advantage. Thus cells with increased malignant character are progressively selected. Development of familial adenomatous polyposis is a good example for multistep progression. Mutations in the APC gene are inherited from parents.
By the time the patient becomes adult, there will be different dysplastic aberrant crypts in the large intestine. Some of the cells will get somatic mutations in the K-Ras gene; these will progress to form adenomas.
Further mutation in TGF gene or p53 gene or Bax gene will give the push for the development of malignancy. Action of Chemical Carcinogens Chemical carcinogens are usually ingested as procarcinogens.
They are metabolised in the body, usually in liver, to become the active carcinogen, e.g. 2-acetyl amino fluorene (AAF) when ingested, is metabolized to produce the ultimate carcinogen, sulfate ester of N-hydroxy-AAF.
The enzymes responsible for the activation of procarcinogens are cytochrome P-450 system. On the other hand, direct carcinogens are the ones which interact directly with the target molecules, e.g. methyl cholanthrene.
Mechanisms of action of chemical carcinogens are:
(a) Carcinogens are generally electrophiles (molecules deficient in electrons); they readily attack nucleophilic (electron rich) groups of DNA.
(b) Carcinogens may bind covalently to cellular DNA. N2, N3, and N7 atoms of guanine are highly prone to addition of carcinogen groups.
(c) These changes will lead to DNA alterations, in spite of DNA repair, with increased probability of mutations. Chemical carcinogens may produce the cancer: (a) At the site of exposure.
Viruses producing tumors in animals Virus Nucleic acid of virus Host Type of tumor produced Papova virus group SV-40 Papilloma Marek DNA DNA Mouse Sarcoma Rabbit DNA Retrovirus type C Gross Rous Retrovirus type B Bittner RNA RNA Chicken Mouse Avian Papilloma Lymphoma Leukemia, Sarcoma RNA Mouse Mammary tumor cancer in tobacco chewers, skin cancer in tar workers. (b) At the site of metabolism, e.g. liver cancer produced by aflatoxin. (c) At the site of elimination, e.g. bladder cancer in persons working with aromatic dyes.
Physical Carcinogens X-ray, gamma-ray and UV-ray may cause: (a) formation of pyrimidine dimers, (b) apurinic sites with consequent break in DNA, and (c) formation of free radicals and superoxides which cause DNA break, leading to somatic mutations.
Exposure of X-ray in fetal life will increase the risk of leukemia in childhood. In population studies, 1 rad per year will increase the cancer incidence by 40/ million people per year.
Antimutagens i. These are substances which will interfere with tumor promotion. Vitamin A and carotenoids are shown to reverse precancerous conditions.
ii. Vitamin E acts as an antioxidant, preventing the damage made by free radicals and superoxides.
iii. Vitamin C regularly given to persons working with aniline prevented the production of new cancer cases.
iv. Tubers, beans and leafy vegetables are sjhown to interrupt tumor promotion.
v. Curcumin, the yellow substance in Turmeric is known to prevent mutations.
vi. The beneficial effect of the fibre content of the diet is Low protein, low fat, diet decreases the risk of cancer in animal.