Most of the human cancers are caused by certain chemical, physical and biological agents, collectively known as carcinogens, which damage DNA leading to mutations in the growth regulatory genes including Oncogenes and Tumour Suppressor Genes. To trace origin of cancer to a particular carcinogen is not an easy job as the latent period between exposure to a carcinogen and development of cancer is quite long. Moreover, the degree and nature of exposure is usually unclear or poorly documented.
In 1915, two Japanese scientists named Katsusaburo Yamagiwa and Koichi Ishikawa induced cancer in rabbits by painting coal tar on their ears. Later, in 1925, Ernest L. Kennaway of England isolated certain chemicals from coal tar and demonstrated their carcinogenic effect. In another experiment, butter yellow (a dye used to give yellow colour to butter) was fed to rats for few weeks and it was found that these rats developed cancer in their liver. It was also observed that the workers of aniline dye factories were having much higher incidence of bladder cancer. Followed by such observations, certain programmes were initiated all over the world to identify cancer-causing chemicals. Carcinogenic activity of a chemical can be measured by its ability to cause cancer in the test animals. Specific strains of mice are used in such experiments. The chemical is either painted over skin or injected below the skin in test animals according to a pre-determined schedule and they are kept under observation. Over a period of time, many chemical carcinogens have been identified.
Tobacco is considered as the most recognised source of chemical carcinogens. Tobacco smoke generates more than 2000 chemical compounds, most of which are carcinogens. The level of Carbon monoxide in tobacco smoke is eight times higher than the maximum permissible limits. Tobacco smoke also contains Nicotine, which is one of the major cancer promoters. Tobacco tar contains hydrocarbons such as Nitrosamines, Benzene, Benzopyrenes and other carcinogenic compounds. Tobacco chewing & smoking can cause many cancers including those of the lung, mouth, larynx, stomach and bladder. India has the highest rate of oral cancers in the world due to wide spread habit of tobacco chewing. The tobacco related cancers account for more than one third of all the cancer.
The polluted environment is another major source of chemical carcinogens. Fumes emitted by vehicles contain many toxic chemical compounds, most of which are carcinogens such as Carbon monoxide, Lead, Nitrous oxide, Benzene and many other toxic volatile compounds. The list of chemical carcinogens also includes salts of heavy metals and complex organic chemicals.
Most of the industrial toxic chemicals and heavy metals such as Lead, Arsenic, Mercury, Aluminium, Nickel and Cadmium having carcinogenic activity may find their way into the human body. The bioaccumulation of these industrial carcinogens in different tissues & organs of the human body can cause cancer by damaging the DNA.
Farmers and agricultural workers are directly exposed to pesticides such as Carbaryl, Chlordane, Diazinon, Dichlorvos, Dichloro-diphenyl-trichloroethane (DDT), Lindane, Malathion and Toxaphene, which are carcinogens.
Chlorine is commonly used to purify the drinking water. Chlorine can form cancer-causing compounds in the drinking water such as Chloroform and Trichloroethylene.
Food containing the residues of pesticides & herbicides is a major source of chemical carcinogens. Most of the food additives like preservatives, sweeteners and colours can cause cancer. Butylated hydroxytoluene used as a preservative can cause liver cancer. Saccharin and cyclamates used as artificial sweeteners can cause cancer of the bladder. Another artificial sweetener called aspartame, which is used in many food products can cause brain tumours. Other food additives, which are known to cause cancer, include Blue Dye No 2, Red Dye No. 3, Propyl gallate, Gentian violet, Nitro furans and Aldicarb.
Exposure to ionising radiation such as X-rays, Gamma rays and particle radiation from radioactive substances form highly reactive ions in the exposed cells that can rupture the DNA strands, causing mutations in the genes, leading to the development of cancer. It has been observed that the exposures to even low-levels of ionising radiation can cause cancer. In earlier days, the radiologists used to develop thyroid tumours and leukaemias because they were not protected from the X-rays. According to Ernest Sternglass, a professor of radiation physics at the University of Pittsburgh, low-levels of radiation from X rays, background radioactivity and nuclear reactor fallout can cause cancer.
Radioactive waves emitted in the atomic explosions have a significant carcinogenic effect. Most of the survivors of the 1945 atomic bomb explosions at Hiroshima and Nagasaki in Japan developed leukaemia due to exposure to the atomic radiation. After the Chernobyl nuclear accident in 1986, the incidence of the thyroid cancer increased 100 times among the children living in the most exposed areas of Ukraine, Belarus and Russia.
Solar radiation (ultraviolet B and ultraviolet C) is the causative factor in about 40 per cent of the skin cancers. Ultraviolet radiation induces permanent mutation in the tumour suppressor gene (p53 gene) in the exposed cells that causes skin cancer. Exposure to ultraviolet radiation is increasing, day-by-day, due to the expanding ozone hole in the earth’s upper atmosphere. The people with darker skin are protected from ultraviolet radiation due to presence of a pigment called Melanin in their skin. Caucasians of Australia are the worst affected from ultraviolet radiation, due to over exposure to sunlight and the least amount of melanin in their skin.
Exposure to electromagnetic radiation, emitted by man-made technological devices and installations can cause cancer. The electromagnetic fields (EMFs) generated by fluorescent lights, electrical wirings, electric motors, food mixers, hair dryers, heaters, electric shavers, vacuum cleaners, microwave ovens, televisions, computers, video terminals and cell phones, etc. emit 30 to 100 times greater EMFs than the permissible limits. Ordinary home appliances generate large cumulative electromagnetic radiation due to proximity of the user to these appliances. The EMFs from these appliances drop off at a distance of about 16 feet but the users usually stand or sit closer to the these appliances. It has been observed that prolonged exposure to electromagnetic fields causes mutations in the genes. According to David A. Savitz of the University of North Carolina School of Public Health, children living near the high-tension power lines have twofold higher risk of developing cancer, especially brain tumour & leukaemia. Research done at the Veteran’s Administration Medical Centre in Loma Linda, California has shown that EMFs stimulate the activity of an enzyme called Ornithine decarboxylase that promotes the growth of malignant cells.
Physical irritants such as chronic abrasion of mucus membrane of the gastrointestinal tract by some food item or abrasion of the buccal mucosa by an ill-fitted denture can lead to the development of cancer. The worn out cells in these tissues are to be replaced by the new cells, formed as a result of rapid mitosis (cell division) that increases the chance of mutations in the genes, thus increasing the risk of developing cancer.
Viruses are known to cause cancer in animals but their role in the genesis of human cancer is a subject of debate. It is difficult for the scientists to prove that viruses cause human cancer, because direct experiments on the human beings are not allowed. Some of the evidences suggest the causative role of viruses in the human cancers. About 90 per cent cases of nasopharyngeal carcinoma have the antigens of Epstein-Barr virus (EBV). There is a link between EBV and Burkitt’s lymphoma. Studies have suggested an association between EBV and the testicular tumours. Epstein-Barr virus is also associated with leiomyoma in children. Similarly, Hepatitis B and Hepatitis C viruses are known to enhance the risk of hepatocellular carcinoma. Human immunodeficiency virus (HIV) is associated with non-Hodgkin’s lymphoma, Kaposi’s sarcoma and cancers of the cervix & anus. The findings of DNA sequences of human herpes virus-8 (HHV-8) in Kaposi’s sarcoma and multiple myeloma support the causative role of herpes virus in cancer. Sexually transmitted human papilloma virus (HPV) is a major risk factor of cervical & anal cancers.
***Virus is a sub microscopic entity consisting of a molecule of DNA or RNA covered by a protective protein coating called capsid. It has been observed that the DNA strands of virus insert directly into one of the chromosomes of the animal cell, causing mutations that can lead to the development of cancer. Some of the RNA viruses are found to carry an enzyme called reverse transcriptase that transcribes RNA to DNA. The strands of transcribed DNA then insert into the chromosomes of the animal cell, causing mutations in the genes.
Hereditary predisposition to a specific cancer is linked to the specific molecular events within the genes. A strong family history in some cancers indicates the existence of hereditary cancer syndromes such as familial retinoblastoma, familial adenomatous polyposis, multiple endocrine neoplasia syndrome and hereditary breast & ovarian cancer syndromes. Genetic mutations are commonly associated with the breast and ovarian cancers. Studies have shown that more than 40 per cent of breast cancers occurring below the age of 30 years are due to inheritance of the abnormal gene known as BRCA-1, which is located on chromosome 17. This gene was first identified in 1990. The BRCA-1 and BRCA-2 genes are found in the members of those families, who have tendency to develop breast and ovarian cancers at an early age. Studies have revealed that inheritance of the BRCA-1 gene confers a lifelong risk of the breast cancer (85 per cent) and ovarian cancer (50 per cent). It has been observed that the members of those families who are predisposed to a particular cancer, have one or more mutated oncogenes in their inherited genome. Therefore fewer additional mutations are required in these persons for the cancer to develop.
Geography plays a role in the development of cancer. It has been observed that the incidence of oesophageal cancer is particularly high in the geographical band covering South-East Africa, Iran, Afghanistan, Central Asia, Mongolia and North China. The incidence of pancreatic cancer is higher in the Western countries and lower in Japan. On the other hand, the stomach cancer is more common in Japan as compared to the Western countries. Similarly, the incidence of breast cancer varies appreciably in different parts of the world, being higher in the USA and lower in the Orient. Studies from Norway, Canada, USA and Australia have shown that the incidence of malignant melanoma increases considerably as one approach the equator, probably due to the greater exposure to ultraviolet radiation.
Generally, it is considered that cancer occurs in middle and old age. We should know that certain cancers are more common in childhood. Between 30 to 50 years of age, cancer is three times more common in females as compared to males whereas males are having a greater risk of cancer than females in the age group of 60 to 80 years.
An additional cause of cancer that has emerged recently is the exposure to chemotherapy and radiotherapy. The aggressive use of chemotherapy and radiotherapy, especially combination of the two modalities is associated with leukaemia and other cancers. It has been observed that the cancer developed due to chemotherapy and radiotherapy is more aggressive in character with poor prognosis.