Carcinogen
A carcinogen is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruses and bacteria. Most carcinogens act by creating mutations in DNA that disrupt a cell's normal processes for regulating growth, leading to uncontrolled cellular proliferation. This occurs when the cell's DNA repair processes fail to identify DNA damage allowing the defect to be passed down to daughter cells. The damage accumulates over time. This is typically a multi-step process during which the regulatory mechanisms within the cell are gradually dismantled allowing for unchecked cellular division.
The specific mechanisms for carcinogenic activity is unique to each agent and cell type. Carcinogens can be broadly categorized, however, as activation-dependent and activation-independent which relate to the agent's ability to engage directly with DNA. Activation-dependent agents are relatively inert in their original form, but are bioactivated in the body into metabolites or intermediaries capable of damaging human DNA. These are also known as "indirect-acting" carcinogens. Examples of activation-dependent carcinogens include polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, and mycotoxins. Activation-independent carcinogens, or "direct-acting" carcinogens, are those that are capable of directly damaging DNA without any modification to their molecular structure. These agents typically include electrophilic groups that react readily with the net negative charge of DNA molecules. Examples of activation-independent carcinogens include ultraviolet light, ionizing radiation and alkylating agents.
The time from exposure to a carcinogen to the development of cancer is known as the latency period. For most solid tumors in humans the latency period is between 10 and 40 years depending on cancer type. For blood cancers, the latency period may be as short as two. Due to prolonged latency periods identification of carcinogens can be challenging.
A number of organizations review and evaluate the cumulative scientific evidence regarding the potential carcinogenicity of specific substances. Foremost among these is the International Agency for Research on Cancer. IARC routinely publishes monographs in which specific substances are evaluated for their potential carcinogenicity to humans and subsequently categorized into one of four groupings: Group 1: Carcinogenic to humans, Group 2A: Probably carcinogenic to humans, Group 2B: Possibly carcinogenic to humans and Group 3: Not classifiable as to its carcinogenicity to humans. Other organizations that evaluate the carcinogenicity of substances include the National Toxicology Program of the US Public Health Service, NIOSH, the American Conference of Governmental Industrial Hygienists and others.
There are numerous sources of exposures to carcinogens including ultraviolet radiation from the sun, radon gas emitted in residential basements, environmental contaminants such as chlordecone, cigarette smoke and ingestion of some types of foods such as alcohol and processed meats. Occupational exposures represent a major source of carcinogens with an estimated 666,000 annual fatalities worldwide attributable to work related cancers. According to NIOSH, 3-6% of cancers worldwide are due to occupational exposures. Well established occupational carcinogens include vinyl chloride and hemangiosarcoma of the liver, benzene and leukemia, aniline dyes and bladder cancer, asbestos and mesothelioma, polycyclic aromatic hydrocarbons and scrotal cancer among chimney sweeps to name a few.
Radiation
Ionizing Radiation
identifies all radionuclides as carcinogens, although the nature of the emitted radiation, its consequent capacity to cause ionization in tissues, and the magnitude of radiation exposure, determine the potential hazard. Carcinogenicity of radiation depends on the type of radiation, type of exposure, and penetration. For example, alpha radiation has low penetration and is not a hazard outside the body, but emitters are carcinogenic when inhaled or ingested. For example, Thorotrast, a suspension previously used as a contrast medium in x-ray diagnostics, is a potent human carcinogen known because of its retention within various organs and persistent emission of alpha particles. Low-level ionizing radiation may induce irreparable DNA damage leading to pre-mature aging and cancer.Non-ionizing radiation
Not all types of electromagnetic radiation are carcinogenic. Low-energy waves on the electromagnetic spectrum including radio waves, microwaves, infrared radiation and visible light are thought not to be, because they have insufficient energy to break chemical bonds. Evidence for carcinogenic effects of non-ionizing radiation is generally inconclusive, though there are some documented cases of radar technicians with prolonged high exposure experiencing significantly higher cancer incidence.Higher-energy radiation, including ultraviolet radiation generally is carcinogenic, if received in sufficient doses. For most people, ultraviolet radiations from sunlight is the most common cause of skin cancer. In Australia, where people with pale skin are often exposed to strong sunlight, melanoma is the most common cancer diagnosed in people aged 15–44 years.
Substances or foods irradiated with electrons or electromagnetic radiation are not carcinogenic. In contrast, non-electromagnetic neutron radiation produced inside nuclear reactors can produce secondary radiation through nuclear transmutation.
Common carcinogens associated with food
Alcohol
is a carcinogen of the head and neck, esophagus, liver, colon and rectum, and breast. It has a synergistic effect with tobacco smoke in the development of head and neck cancers. In the United States approximately 6% of cancers and 4% of cancer deaths are attributable to alcohol use.Processed meats
Chemicals used in processed and cured meat such as some brands of bacon, sausages and ham may produce carcinogens. For example, nitrites used as food preservatives in cured meat such as bacon have also been noted as being carcinogenic with demographic links, but not causation, to colon cancer.Meats cooked at high temperatures
Cooking food at high temperatures, for example grilling or barbecuing meats, may also lead to the formation of minute quantities of many potent carcinogens that are comparable to those found in cigarette smoke. Charring of food looks like coking and tobacco pyrolysis, and produces carcinogens. There are several carcinogenic pyrolysis products, such as polynuclear aromatic hydrocarbons, which are converted by human enzymes into epoxides, which attach permanently to DNA. Pre-cooking meats in a microwave oven for 2–3 minutes before grilling shortens the time on the hot pan, and removes heterocyclic amine precursors, which can help minimize the formation of these carcinogens.Acrylamide in foods
Frying, grilling or broiling food at high temperatures, especially starchy foods, until a toasted crust is formed generates acrylamides. This discovery in 2002 led to international health concerns. Subsequent research has however found that it is not likely that the acrylamides in burnt or well-cooked food cause cancer in humans; Cancer Research UK categorizes the idea that burnt food causes cancer as a "myth".Biologic Agents
Several biologic agents are known carcinogens.Aflatoxin B1, a toxin produced by the fungus Aspergillus flavus which is a common contaminant of stored grains and nuts is a known cause of hepatocellular cancer. The bacteria H. Pylori is known to cause stomach cancer and MALT lymphoma. Hepatitis B and C are associated with the development of hepatocellular cancer. HPV is the primary cause of cervical cancer.
Cigarette smoke
Tobacco smoke contains at least 70 known carcinogens and is implicated in the development of numerous types of cancers including cancers of the lung, larynx, esophagus, stomach, kidney, pancreas, liver, bladder, cervix, colon, rectum and blood. Potent carcinogens found in cigarette smoke include polycyclic aromatic hydrocarbons, benzene, and nitrosamine.Occupational carcinogens
Given that populations of workers are more likely to have consistent, often high level exposures to chemicals rarely encountered in normal life, much of the evidence for the carcinogenicity of specific agents is derived from studies of workers.Selected carcinogens
| Carcinogen | Associated cancer sites or types | Occupational uses or sources |
| Arsenic and its compounds | ||
| Asbestos | Not in widespread use, but found in:
| |
| Benzene | ||
| Beryllium and its compounds | ||
| Cadmium and its compounds | ||
| Hexavalent chromium compounds | ||
| Nitrosamines | ||
| Ethylene oxide | ||
| Nickel | ||
| Radon and its decay products | ||
| Vinyl chloride | ||
| Shift work that involvescircadian disruption | ||
| Involuntary smoking | ||
| Radium-226, Radium-224, Plutonium-238, Plutonium-239 and other alpha particle emitters with high atomic weight |
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| Unless otherwise specified, ref is: | - | - |