Causes of cancer


Cancer is caused by genetic changes leading to uncontrolled cell growth and tumor formation. The basic cause of sporadic cancers is DNA damage and genomic instability. A minority of cancers are due to inherited genetic mutations. Most cancers are related to environmental, lifestyle, or behavioral exposures. Cancer is generally not contagious in humans, though it can be caused by oncoviruses and cancer bacteria. The term "environmental", as used by cancer researchers, refers to everything outside the body that interacts with humans. The environment is not limited to the biophysical environment, but also includes lifestyle and behavioral factors.
Over one third of cancer deaths worldwide are potentially avoidable by reducing exposure to known factors. Common environmental factors that contribute to cancer death include exposure to different chemical and physical agents, environmental pollutants, diet and obesity, infections, and radiation. These factors act, at least partly, by altering the function of genes within cells. Typically many such genetic changes are required before cancer develops. Aging has been repeatedly and consistently regarded as an important aspect to consider when evaluating the risk factors for the development of particular cancers. Many molecular and cellular changes involved in the development of cancer accumulate during the aging process and eventually manifest as cancer.

Genetics

Although there are over 50 identifiable hereditary forms of cancer, less than 0.3% of the population are carriers of a cancer-related genetic mutation and these make up less than 3–10% of all cancer cases. The vast majority of cancers are non-hereditary. Hereditary cancers are primarily caused by an inherited genetic defect. A cancer syndrome or family cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predisposes the affected individuals to the development of cancers and may also cause the early onset of these cancers. Although cancer syndromes exhibit an increased risk of cancer, the risk varies. For some of these diseases, cancer is not the primary feature and is a rare consequence.
Many of the cancer syndrome cases are caused by mutations in tumor suppressor genes that regulate cell growth. Other common mutations alter the function of DNA repair genes, oncogenes and genes involved in the production of blood vessels. Certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer. Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of colon cancer cases. In many cases, genetic testing can be used to identify mutated genes or chromosomes that are passed through generations.

Cancer syndromes

Particular substances, known as carcinogens, have been linked to specific types of cancer. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise in both natural and synthetic substances. It is estimated that approximately 20,000 cancer deaths and 40,000 new cases of cancer each year in the U.S. are attributable to occupation. Every year, at least 200,000 people die worldwide from cancer related to their workplace. Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling asbestos fibers and tobacco smoke, or leukemia from exposure to benzene at their workplaces. Cancer related to one's occupation is believed to represent between 2–20% of all cases. Most cancer deaths caused by occupational risk factors occur in the developed world. Job stress does not appear to be a significant factor at least in lung, colorectal, breast and prostate cancers. Participation in Operation Ranchhand in Vietnam during the Vietnam war, or living near a golf course, or living on a farm would increase the risk of non-Hodgkins lymphoma due to exposure to the chemical 2,4-D. When 2,4-D is mixed with another chemical pesticide or herbicide, 2,4-T, at a 50:50 ratio, they are collectively known as Agent Orange.

Air pollution

Smoking

is associated with many forms of cancer, and causes 80% of lung cancer. Decades of research has demonstrated the link between tobacco use and cancer in the lung, larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas. There is some evidence suggesting a small increased risk of developing myeloid leukemia, squamous cell sinonasal cancer, liver cancer, colorectal cancer, cancers of the gallbladder, the adrenal gland, the small intestine, and various childhood cancers. Seven toxicants in cigarette smoke have been identified that are most associated with respiratory tract carcinogenesis. The mechanism of action of two of them, acrylonitrile and acrolein, appears to involve oxidative stress and oxidative DNA damage. The other five toxicants, acetaldehyde, cadmium, ethylene oxide, formaldehyde and isoprene act through various mechanisms including direct interaction with DNA. Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons. Tobacco is responsible for about one in three of all cancer deaths in the developed world, and about one in five worldwide. Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990. However, the numbers of smokers worldwide is still rising, leading to what some organizations have described as the tobacco epidemic.
Electronic cigarettes or e-cigarettes are handheld electronic devices that simulate the feeling of tobacco smoking. Daily long-term use of high voltage electronic cigarettes may generate formaldehyde-forming chemicals at a greater level than smoking, which was determined to be a lifetime cancer risk of approximately 5 to 15 times greater than smoking. However, the overall safety and long-term health effects of electronic cigarettes is still uncertain.

Materials

Some substances cause cancer primarily through their physical, rather than chemical, effects on cells. A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers which are a major cause of mesothelioma, which is a cancer of the serous membrane, usually the serous membrane surrounding the lungs. Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers such as wollastonite, attapulgite, glass wool, and rock wool, are believed to have similar effects. Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel, and crystalline silica. Usually, physical carcinogens must get inside the body and require years of exposure to develop cancer. Common occupational carcinogens include:
Many different lifestyle factors contribute to increasing cancer risk. Together, diet and obesity are related to approximately 30–35% of cancer deaths. Dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains, and fish, and avoidance of processed meat, red meat, animal fats, and refined carbohydrates. The evidence to support these dietary changes is not definitive.

Alcohol

is an example of a chemical carcinogen. The World Health Organization has classified alcohol as a Group 1 carcinogen. In Western Europe 10% of cancers in males and 3% of cancers in females are attributed to alcohol. Worldwide, 3.6% of all cancer cases and 3.5% of cancer deaths are attributable to alcohol. In particular, alcohol use has been shown to increase the risk of developing cancers of the mouth, esophagus, pharynx, larynx, stomach, liver, ovaries, and colon. The main mechanism of cancer development involves increased exposure to acetaldehyde, a carcinogen and breakdown product of ethanol. Acetaldehyde induces DNA interstrand crosslinks, a form of DNA damage. These can be repaired by an inaccurate replication-coupled DNA repair pathway. This repair pathway results in increased mutation frequency and altered mutational spectrum. Other mechanisms have been proposed, including alcohol-related nutritional deficiencies, changes in DNA methylation, and induction of oxidative stress in tissues.

Diet

Some specific foods have been linked to specific cancers. Studies have shown that individuals that eat red or processed meat have a higher risk of developing breast cancer, prostate cancer, and pancreatic cancer. This may be partially explained by the presence of carcinogens in food cooked at high temperatures. Several risk factors for the development of colorectal cancer include high intake of fat, alcohol, red and processed meats, obesity, and lack of physical exercise. A high-salt diet is linked to gastric cancer. Aflatoxin B1, a frequent food contaminate, is associated with liver cancer. Betel nut chewing has been shown to cause oral cancers.
The relationship between diet and the development of particular cancers may partly explain differences in cancer incidence in different countries. For example, gastric cancer is more common in Japan due to the frequency of high-salt diets and colon cancer is more common in the United States due to the increased intake of processed and red meats. Immigrant communities tend to develop the cancer risk profile of their new country, often within one to two generations, suggesting a substantial link between diet and cancer.
When deoxycholate was added to the food of mice so that their feces contained deoxycholate at about the same level present in feces of human on a high fat diet, 45% to 56% of the mice developed colon cancer over the next 10 months, while none of the mice on a diet without deoxycholate developed cancer. A recent prospective human study investigating the relationship between microbial metabolites and cancer found a strong correlation between circulating deoxycholate as well as other specific bile acids and colorectal cancer risk in women.