International Agency for Research on Cancer

IARCInternational Agency for Research on Cancer (IARC)Group 4
European Prospective Investigation into Cancer and Nutrition. European Organisation for Research and Treatment of Cancer (EORTC). Genotoxic. Mutagen. National Cancer Institute (US). Toxicology.


mutationsgenetic mutationmutated
Measuring this rate is important in predicting the rate at which people may develop cancer. Point mutations may arise from spontaneous mutations that occur during DNA replication. The rate of mutation may be increased by mutagens. Mutagens can be physical, such as radiation from UV rays, X-rays or extreme heat, or chemical (molecules that misplace base pairs or disrupt the helical shape of DNA). Mutagens associated with cancers are often studied to learn about cancer and its prevention. A hypomorphic mutation is a mutation which results in lowered gene expression. Usually, hypomorphic mutations are recessive, but haploinsufficiency causes some alleles to be dominant.


herbicidesweed killerherbicidal
Plants have developed resistance to atrazine and to ALS-inhibitors, and more recently, to glyphosate herbicides. Marestail is one weed that has developed glyphosate resistance. Glyphosate-resistant weeds are present in the vast majority of soybean, cotton and corn farms in some U.S. states. Weeds that can resist multiple other herbicides are spreading. Few new herbicides are near commercialization, and none with a molecular mode of action for which there is no resistance. Because most herbicides could not kill all weeds, farmers rotated crops and herbicides to stop resistant weeds.


carbohydratessaccharidecomplex carbohydrates
It is abundant in cereals (wheat, maize, rice), potatoes, and processed food based on cereal flour, such as bread, pizza or pasta. Sugars appear in human diet mainly as table sugar (sucrose, extracted from sugarcane or sugar beets), lactose (abundant in milk), glucose and fructose, both of which occur naturally in honey, many fruits, and some vegetables. Table sugar, milk, or honey are often added to drinks and many prepared foods such as jam, biscuits and cakes. Cellulose, a polysaccharide found in the cell walls of all plants, is one of the main components of insoluble dietary fiber.


Monsanto CompanyMonsanto Chemical CompanyCalgene
Over 8,000 cancer patients are suing Monsanto in numerous state courts for failure to warn the public about the risk of cancer associated with the glyphosate-based weedkiller Roundup after the IARC report in 2015 linking glyphosate to cancer in humans. Monsanto denies that Roundup is carcinogenic. In March 2017, 40 plaintiffs filed a lawsuit at the Alameda County Superior Court, a branch of the California Superior Court, asking for damages caused by the company's glyphosate-based weed-killers, including Roundup, and demanding a jury trial. On August 10, 2018, Monsanto lost the first decided case.


deoxyribonucleic aciddouble-stranded DNAdsDNA
DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases. On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks. A typical human cell contains about 150,000 bases that have suffered oxidative damage.


chromosomeschromosomalChromosomal number
Usually, this will make the cell initiate apoptosis leading to its own death, but sometimes mutations in the cell hamper this process and thus cause progression of cancer. Some use the term chromosome in a wider sense, to refer to the individualized portions of chromatin in cells, either visible or not under light microscopy. Others use the concept in a narrower sense, to refer to the individualized portions of chromatin during cell division, visible under light microscopy due to high condensation. The word chromosome comes from the Greek χρῶμα (chroma, "colour") and σῶμα (soma, "body"), describing their strong staining by particular dyes.


Under this model, cancer arises as the result of a single, isolated event, rather than the slow accumulation of multiple mutations. Many mutagens are also carcinogens, but some carcinogens are not mutagens. Examples of carcinogens that are not mutagens include alcohol and estrogen. These are thought to promote cancers through their stimulating effect on the rate of cell mitosis. Faster rates of mitosis increasingly leave fewer opportunities for repair enzymes to repair damaged DNA during DNA replication, increasing the likelihood of a genetic mistake.


Mutations come from errors made during the replication of DNA or from exposure to mutagens. Mutation rates vary widely among different species of bacteria and even among different clones of a single species of bacteria. Genetic changes in bacterial genomes come from either random mutation during replication or "stress-directed mutation", where genes involved in a particular growth-limiting process have an increased mutation rate. Some bacteria also transfer genetic material between cells. This can occur in three main ways. First, bacteria can take up exogenous DNA from their environment, in a process called transformation.

World Health Organization

WHOWorld Health OrganisationWorld Health Organization (WHO)
He claimed that this classification did not take into account the extent of exposure: for example, red meat is qualified as probably carcinogenic, but the quantity of consumed red meat at which it could become dangerous is not specified. Controversies have erupted multiple times when the IARC has classified many things as Class 2a (probable carcinogens), including cell phone signals, glyphosate, drinking hot beverages, and working as a barber. Political pressure from China has led to Taiwan being barred from membership of the WHO and other UN-affiliated organizations, and in both 2017 and 2018 the WHO refused to allow Taiwanese delegates to attend the WHO annual assembly.


folic acidfolate biosynthesisone carbon pool by folate
The second study reported no significant increase or decrease in total cancer incidence, colorectal cancer, other gastrointestinal cancer, genitourinary cancer, lung cancer or hematological malignancies in people who were consuming folic acid supplements. A third supplementation meta-analysis limited to reporting only on colorectal cancer incidence showed that folic acid treatment was not associated with colorectal cancer risk. Folate is important for cells and tissues that divide rapidly. Cancer cells divide rapidly, and drugs that interfere with folate metabolism are used to treat cancer.


Cancer-related fatigue. Leukaemia information from Cancer Research UK.


Processes that increase the rate of changes in DNA are called mutagenic: mutagenic chemicals promote errors in DNA replication, often by interfering with the structure of base-pairing, while UV radiation induces mutations by causing damage to the DNA structure. Chemical damage to DNA occurs naturally as well and cells use DNA repair mechanisms to repair mismatches and breaks. The repair does not, however, always restore the original sequence. In organisms that use chromosomal crossover to exchange DNA and recombine genes, errors in alignment during meiosis can also cause mutations.

Polycyclic aromatic hydrocarbon

polycyclic aromatic hydrocarbonsPAHsPAH
Some carcinogenic PAHs are genotoxic and induce mutations that initiate cancer; others are not genotoxic and instead affect cancer promotion or progression. PAHs that affect cancer initiation are typically first chemically modified by enzymes into metabolites that react with DNA, leading to mutations. When the DNA sequence is altered in genes that regulate cell replication, cancer can result. Mutagenic PAHs, such as benzo[a]pyrene, usually have four or more aromatic rings as well as a "bay region", a structural pocket that increases reactivity of the molecule to the metabolizing enzymes. Mutagenic metabolites of PAHs include diol epoxides, quinones, and radical PAH cations.


AsAs 2 Arsenate
The International Agency for Research on Cancer (IARC) recognizes arsenic and inorganic arsenic compounds as group 1 carcinogens, and the EU lists arsenic trioxide, arsenic pentoxide, and arsenate salts as category 1 carcinogens. Arsenic is known to cause arsenicosis when present in drinking water, "the most common species being arsenate [; As(V)] and arsenite [H 3 AsO 3 ; As(III)]". In the United States since 2006, the maximum concentration in drinking water allowed by the Environmental Protection Agency (EPA) is 10 ppb and the FDA set the same standard in 2005 for bottled water. The Department of Environmental Protection for New Jersey set a drinking water limit of 5 ppb in 2006.


vegetablessalad vegetablewild vegetables
Throughout recorded history, the rich have been able to afford a varied diet including meat, vegetables and fruit, but for poor people, meat was a luxury and the food they ate was very dull, typically comprising mainly some staple product made from rice, rye, barley, wheat, millet or maize. The addition of vegetable matter provided some variety to the diet. The staple diet of the Aztecs in Central America was maize and they cultivated tomatoes, avocados, beans, peppers, pumpkins, squashes, peanuts, and amaranth seeds to supplement their tortillas and porridge. In Peru, the Incas subsisted on maize in the lowlands and potatoes at higher altitudes.


proteinsproteinaceousstructural proteins
Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells, and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific three-dimensional structure that determines its activity.


chemotherapeuticantineoplasticantineoplastic agent
Moreover, these drugs have carcinogenic effects. In the past five decades, multiple studies have shown the carcinogenic effects of exposure to antineoplastic drugs. Similarly, there have been research studies that linked alkylating agents with humans developing leukemias. Studies have reported elevated risk of breast cancer, nonmelanoma skin cancer, and cancer of the rectum among nurses who are exposed to these drugs. Other investigations revealed that there is a potential genotoxic effect from anti-neoplastic drugs to workers in health care settings.


Cancer. Support hormone-sensitive breast cancers (see section below). Lung function. Promotes lung function by supporting alveoli (in rodents but probably in humans). Uterus lining. Estrogen together with progesterone promotes and maintains the uterus lining in preparation for implantation of fertilized egg and maintenance of uterus function during gestation period, also upregulates oxytocin receptor in myometrium. Ovulation. Surge in estrogen level induces the release of luteinizing hormone, which then triggers ovulation by releasing the egg from the Graafian follicle in the ovary. Sexual behavior. Promotes sexual receptivity in estrus, and induces lordosis behavior.

Glyphosate-based herbicides

glyphosate formulationglyphosate-based herbicideglyphosate-based weed-killing products
Attempts were made to apply them to row crops, but problems with crop damage kept glyphosate-based herbicides from being widely used for this purpose. In the US, use of glyphosate experienced rapid growth following the commercial introduction of a glyphosate-resistant soybean in 1996. Between 1990 and 1996 sales of RoundUp increased around 20% per year. it is used in over 160 countries. RoundUp is used most heavily on corn, soy, and cotton crops that have been genetically modified to withstand the chemical, but since 2012 glyphosate was used in California to treat other crops like almond, peach, cantaloupe, onion, cherry, sweet corn, and citrus.

Malignant transformation

These compounds and their genotoxic effects are listed in the article Cigarette. The top three compounds are acrolein, formaldehyde and acrylonitrile, all known carcinogens. In 2002 the World Health Organizations International Agency for Research on Cancer estimated that 11.9% of human cancers are caused by one of seven viruses (see Oncovirus overview table). These are Epstein-Barr virus (EBV or HHV4); Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8); Hepatitis B and Hepatitis C viruses (HBV and HCV); Human T-lymphotrophic virus 1 (HTLV-1); Merkel cell polyomavirus (MCPyV); and a group of alpha Human papillomaviruses (HPVs).

Mutational signatures

mutational signature
Selected exogenous genotoxins/carcinogens and their mutagen-induced DNA damage and repair mechanisms have been linked to specific molecular signatures. It has a strong transcriptional bias with C>T substitutions enriched on the untranscribed DNA strand. Ultraviolet radiation exposure is the proposed underlying mutagenic mechanism of this signature. This signature is enriched for C>T substitutions on guanine bases due to transcription-coupled nucleotide excision repair. A strong transcriptional strand-bias is present in this signature. Signature 9 has been identified in chronic lymphocytic leukemia and malignant B-cell lymphoma and feature enrichment for T>G transversion events.


L-tryptophanTrptryptophan metabolism
Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a non-polar aromatic amino acid. It is essential in humans, meaning the body cannot synthesize it; it must be obtained from the diet. Tryptophan is also a precursor to the neurotransmitter serotonin, the hormone melatonin and vitamin B3. It is encoded by the codon UGG.

Tobacco smoking

smokingcigarette smokingsmoker
The most important chemicals causing cancer are those that produce DNA damage since such damage appears to be the primary underlying cause of cancer. Cunningham et al. combined the microgram weight of the compound in the smoke of one cigarette with the known genotoxic effect per microgram to identify the most carcinogenic compounds in cigarette smoke. The seven most important carcinogens in tobacco smoke are shown in the table, along with DNA alterations they cause. Cigarette smoking has also been associated with sarcopenia, the age-related loss of muscle mass and strength.


pesticidescrop sprayingchemical pesticides
In Europe, EU legislation has been approved banning the use of highly toxic pesticides including those that are carcinogenic, mutagenic or toxic to reproduction, those that are endocrine-disrupting, and those that are persistent, bioaccumulative and toxic (PBT) or very persistent and very bioaccumulative (vPvB) and measures have been approved to improve the general safety of pesticides across all EU member states. Though pesticide regulations differ from country to country, pesticides, and products on which they were used are traded across international borders.