Cancer in human beings is caused by certain chemical, physical or biological agents, collectively known as carcinogens. Carcinogens damage the DNA, thus causing mutations in the genes that can lead to cancer. It is not easy to trace the origin of a cancer to the particular carcinogen, because the latent period between exposure to a carcinogen and development of cancer is very long. Moreover, degree and nature of exposure to the carcinogen is usually unclear or poorly documented. The full effect of a carcinogen is often established in about a decade and it may take another few years for the development of cancer.
In 1915, two Japanese scientists named Katsusaburo Yamagiwa and Koichi Ishikawa induced cancer in rabbits by using coal tar. Later, in 1925, Ernest L. Kennaway of England isolated some chemicals from coal tar and demonstrated the carcinogenic effect of these chemicals. In another experiment, butter yellow (dye used to give yellow colour to butter) was fed to rats that led to genesis of the liver cancer in these test animals. Similarly, a study revealed that there was a much higher incidence of bladder cancer among the workers of aniline dye factories. Followed by such observations, certain programmes were initiated all over the world to identify various cancer-causing chemicals. Many chemical carcinogens have been identified so far. The carcinogenic activity of a chemical is measured by its ability to cause cancer in the test animals, for which specific strains of mice are used. The chemical is either painted over the skin or injected in the subcutaneous tissue of the test animals according to a pre-determined schedule, after which the animals are kept under observation.
Tobacco is the most recognised source of chemical carcinogens. Tobacco related cancers account for one third of the human cancers. Tobacco smoke generates many chemical compounds, most of which are carcinogenic. Carbon monoxide level in the tobacco smoke is eight times higher than the maximum permissible limit. Tobacco smoke contains nicotine, which is one of the major cancer promoters. Tobacco tar contains certain hydrocarbons such as nitrosamines, benzene, benzopyrenes and many other carcinogenic compounds. The chewing or smoking of tobacco may lead to many cancers including those of the mouth, larynx, lung, stomach and the bladder. India has highest incidence of the oral cavity cancers in the world due to wide spread habit of tobacco-chewing.
Pollution is another major source of chemical carcinogen. Fumes emitted by vehicles contain many toxic compounds, most of which are carcinogenic. These include carbon monoxide, lead, nitrous oxide, benzene and many other toxic volatile compounds. The list of chemical carcinogens further includes complex organic chemicals and salts of heavy metals.
Industrial toxic chemicals and heavy metals such as lead, arsenic, mercury, aluminium, nickel and cadmium having carcinogenic activity may enter and get accumulated in the human body. The bioaccumulation of these industrial carcinogens in different tissues and organs of the body may lead to genesis of cancer by damaging the DNA.
Chlorine, used to purify drinking water, may produce certain carcinogenic compounds in the water including chloroform and trichloroethylene, which have carcinogenic activity.
Farmers and agricultural workers are directly exposed to pesticides, insecticides and herbicides such as Carbaryl, Chlordane, Diazinon, Dichlorvos, Dichloro-diphenyl-trichloroethane (DDT), Lindane, Malathion and Toxaphene, most of which are having carcinogenic activity. The food containing residues of pesticides, insecticides and herbicides is one of the three major causes of cancer.
Most of the food additives including preservatives, sweeteners and colorants have carcinogenic activity. Butylated hydroxytoluene, used as a preservative, may lead to the liver cancer. Saccharin and cyclamates, used as artificial sweeteners, may cause cancer of the bladder. Another artificial sweetener, known as Aspartame, may cause the brain tumours. Other food additives, known to cause cancer, include Blue Dye No. 2, Red Dye No. 3, Propyl gallate, Gentian violet, Nitrofurans and Aldicarb.
Recent studies have also concluded that the ink used to print receipt in most shops also have carcinogenic properties.
Ionising radiation emitted by X-rays, gamma rays and particle radiation emitted by radioactive substances possess carcinogenic activity. The ionising radiation produce highly reactive ions in the exposed cells that rupture the DNA strands leading to mutations in the genes. It has been observed that exposure to even low levels of ionising radiation lead to genesis of cancer. For example, in earlier days, many radiologists developed the thyroid tumour and leukaemia because they were not protected from the X-rays. Ernest Sternglass, professor of Radiation Physics at the University of Pittsburgh, has confirmed that low levels of radiation from X-rays, background radioactivity and nuclear reactor fallout may cause cancer.
Radioactive waves emitted by atomic explosion have a significant carcinogenic effect. Survivors of the 1945 atomic bomb explosions at Hiroshima and Nagasaki in Japan had manifold higher incidence of leukaemia due to the atomic radiation. Similarly, after the Chernobyl nuclear accident in 1986, the incidence of thyroid cancer increased 100 times among the children living in the most exposed areas of Ukraine, Belarus and Russia.
Ultraviolet radiation induces permanent mutation in the tumour suppressor gene, the p53 gene about which you have read in an earlier blog, in the exposed cells that leads to the skin cancer. The exposure to ultraviolet radiation is increasing day-by-day due to the expanding ozone hole in the earth’s upper atmosphere. It has been observed that the people with darker skin are protected from ultraviolet radiation due to higher concentration of a pigment, known as melanin, in their skin. Caucasians of Australia are the worst affected people from ultraviolet radiation due to over exposure to the sunlight and the least concentration of melanin in their skin.
The electromagnetic fields (EMFs) generated by electrical wirings, electric motors, food mixers, hair dryers, heaters, electric shavers, vacuum cleaners, fluorescent lights, microwave ovens, televisions, computers, video terminals and cell phones emit 30 to 100 times higher EMFs than the maximum permissible limits. Ordinary home appliances generate larger cumulative electromagnetic effect of radiation due to proximity of the user to these appliances. The electromagnetic fields generated from these appliances drop off considerably at a distance of about 16 feet but the users usually stand or sit closer to these appliances. Studies have revealed that prolonged exposure to electromagnetic fields causes mutations in the oncogenes. According to David A. Savitz of the University of North Carolina School of Public Health, the children living near high-tension power lines have twofold higher risk of the brain tumours and the leukaemia. Research done at the Veteran’s Administration Medical Centre in Loma Linda, California has shown that electromagnetic fields stimulate the activity of an enzyme known as ornithine decarboxylase, which promotes growth of the malignant cells.
Physical irritants such as chronic abrasion of mucus membrane lining the gastrointestinal tract by some food items and abrasion of the buccal mucosa by an ill-fitted denture may cause cancer. The damaged cells of injured tissues are replaced by the new cells produced as a result of rapid cell division, thus enhancing chances of mutations in the genes that may lead to genesis of cancer.
Certain viruses are known to cause cancer in animals but role of these viruses in genesis of the human cancer is still a subject of debate. It is difficult for the scientists to prove that viruses have a causative role in the human cancer because direct experiments in the human beings are not allowed, but the evidences suggest the causative role of viruses in the human cancer. For example, 90 per cent cases of nasopharyngeal carcinoma are found to have antigens of Epstein-Barr virus (EBV). There is an established link between Epstein-Barr virus and the Burkitt’s lymphoma. Studies have also revealed an association between Epstein-Barr virus and the testicular tumours. Similarly, the Epstein-Barr virus is associated with leiomyoma in children. Viruses of Hepatitis B and Hepatitis C are known to enhance risk of the hepatocellular carcinoma. Human immuno-deficiency virus (HIV) is associated with the non-Hodgkin’s lymphoma, Kaposi’s sarcoma and cancers of the cervix & the anus. Sexually transmitted Human Papilloma virus (HPV) is a major risk factor of the cervical and the anal cancers. The DNA sequences of the Human Herpes virus-8 (HHV-8) are found in the Kaposi’s sarcoma and the multiple myeloma that supports the causative role of Human Herpes virus in human cancers.
[Virus is a sub microscopic entity consisting of a molecule of DNA or RNA covered by a protective protein coating known as capsid. The DNA strands of virus insert directly into one of the chromosomes of the animal cell, causing mutations in the oncogenes that lead to genesis of cancer. Some RNA viruses carry an enzyme called reverse transcriptase that transcribes the RNA to the DNA. The strands of transcribed DNA then insert into chromosomes of the animal cell, causing mutations in the genes.]
Role of Genes
Theodor Boveri, a German scientist, hypothesised in 1914 that alteration in the genome of a cell lead to genesis of cancer. He proposed that cancer is caused by exchange of genetic material at cellular level. In 1961, Peter Nowell and David Hungerford of the Institute for Cancer Research in Philadelphia observed specific chromosomal abnormalities in patients suffering from the chronic myeloid leukaemia. This altered chromosome was named Philadelphia chromosome (Ph chromosome). Janet Rowley of Chicago disclosed that Ph chromosome is formed by translocation (exchange of parts) between the chromosome 9 and the chromosome 22. It was also observed that translocation of genetic material occurs between the chromosome 8 and the chromosome 14 in the Burkitt’s lymphoma. Later, it was found that most of the cancers exhibit chromosomal abnormalities such as translocation, deletion, insertion and duplication. These chromosomal abnormalities can be seen at the level of an individual gene by using chromosome banding technique and karyotype. Such genetic alterations are now used in the diagnosis and prognosis of cancer, for example loss of long arm of the chromosome 18 in a patient of colon cancer predicts a poor prognosis.
Hereditary predisposition of cancer is linked to specific molecular events within the genes. Strong family history of a particular cancer indicates existence of hereditary cancer syndromes such as the familial retinoblastoma, familial adenomatous polyposis, multiple endocrine neoplasia syndrome and the hereditary breast & ovarian cancer syndromes. Genetic mutations are commonly seen in the breast and the ovarian cancers. Studies have shown that more than 40 per cent cases of the breast cancers occurring below 30 years of age are due to inheritance of BRCA 1 gene, which is located on the chromosome 17. This abnormal gene, first identified in 1990, is found in members of those families, who have the tendency to develop the breast or the ovarian cancers at an early age. Studies have revealed that inheritance of the BRCA 1 gene confers lifelong risk of the breast cancer in 85 per cent cases and that of the ovarian cancer in 50 per cent cases. It is believed that members of those families who are predisposed to a particular cancer, have one or more activated oncogenes in their inherited genome, therefore fewer additional mutations are required in such persons to develop the cancer.
It has been observed that incidence of the oesophageal cancer is much higher in the geographical band covering Southeast Africa, Iran, Afghanistan, Central Asia, Mongolia and North China. Similarly, studies have shown that the incidence of pancreatic cancer is highest in the Western countries and lowest in the Japan. On the other hand, incidence of the stomach cancer is much higher in Japan as compared to the Western countries. The incidence of breast cancer varies considerably in different parts of the world, being highest in the USA and lowest in the Orient. Studies conducted in Norway, Canada, USA and Australia have revealed that incidence of the malignant melanoma increases appreciably as one approaches the Equator, probably due to greater exposure to the ultraviolet rays.
The incidence of cancer is three times higher in women as compared to men during 30 to 50 years of age, whereas men have a greater risk of cancer as compared to women during 60 to 80 years of age. Cancer is generally considered as the disease of middle aged and elderly people, but some cancers are known to affect the children.
An additional cause of cancer that has emerged recently is the use of chemotherapy and radiotherapy for a prior malignancy. The aggressive use of chemotherapy and radiotherapy may lead to genesis of leukaemia & certain other cancers. It has been observed that the latent period is shorter in leukaemia (2 to 5 years) and longer in the solid tumours (10 to 20 years).
Dr. S.P. Kaushal
Sino Vedic Cancer Clinic