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Concept: International Agency for Research on Cancer

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The International Agency for Research on Cancer convened a workshop on the relationship between body fatness and cancer, from which an IARC handbook on the topic will appear. An executive summary of the evidence is presented.

Concepts: International Agency for Research on Cancer

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In November 2014, experts from 16 countries met at the International Agency for Research on Cancer (IARC) to assess the cancer-preventive and adverse effects of different methods of screening for breast cancer. (The members of the working group for volume 15 of the IARC Handbook are listed at the end of the article; affiliations are provided in the Supplementary Appendix, available with the full text of this article at NEJM.org.) This update of the 2002 IARC handbook on breast-cancer screening(1) is timely for several reasons. Recent improvements in treatment outcomes for late-stage breast cancer and concerns regarding overdiagnosis call for reconsideration. . . .

Concepts: Metastatic breast cancer, International Agency for Research on Cancer, Janet Lane-Claypon, Pleural effusion, Metastasis, Chemotherapy, Breast cancer, Cancer

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The widespread distribution of unconventional oil and gas (UO&G) wells and other facilities in the United States potentially exposes millions of people to air and water pollutants, including known or suspected carcinogens. Childhood leukemia is a particular concern because of the disease severity, vulnerable population, and short disease latency. A comprehensive review of carcinogens and leukemogens associated with UO&G development is not available and could inform future exposure monitoring studies and human health assessments. The objective of this analysis was to assess the evidence of carcinogenicity of water contaminants and air pollutants related to UO&G development. We obtained a list of 1177 chemicals in hydraulic fracturing fluids and wastewater from the U.S. Environmental Protection Agency and constructed a list of 143 UO&G-related air pollutants through a review of scientific papers published through 2015 using PubMed and ProQuest databases. We assessed carcinogenicity and evidence of increased risk for leukemia/lymphoma of these chemicals using International Agency for Research on Cancer (IARC) monographs. The majority of compounds (>80%) were not evaluated by IARC and therefore could not be reviewed. Of the 111 potential water contaminants and 29 potential air pollutants evaluated by IARC (119 unique compounds), 49 water and 20 air pollutants were known, probable, or possible human carcinogens (55 unique compounds). A total of 17 water and 11 air pollutants (20 unique compounds) had evidence of increased risk for leukemia/lymphoma, including benzene, 1,3-butadiene, cadmium, diesel exhaust, and several polycyclic aromatic hydrocarbons. Though information on the carcinogenicity of compounds associated with UO&G development was limited, our assessment identified 20 known or suspected carcinogens that could be measured in future studies to advance exposure and risk assessments of cancer-causing agents. Our findings support the need for investigation into the relationship between UO&G development and risk of cancer in general and childhood leukemia in particular.

Concepts: United States Environmental Protection Agency, Polycyclic aromatic hydrocarbon, Assessment, Leukemia, Cancer, Carcinogen, International Agency for Research on Cancer, Benzene

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Classification schemes for carcinogenicity based solely on hazard-identification such as the IARC monograph process and the UN system adopted in the EU have become outmoded. They are based on a concept developed in the 1970s that chemicals could be divided into two classes: carcinogens and non-carcinogens. Categorization in this way places into the same category chemicals and agents with widely differing potencies and modes of action. This is how eating processed meat can fall into the same category as sulfur mustard gas. Approaches based on hazard and risk characterization present an integrated and balanced picture of hazard, dose response and exposure and allow informed risk management decisions to be taken. Because a risk-based decision framework fully considers hazard in the context of dose, potency, and exposure the unintended downsides of a hazard only approach are avoided, e.g., health scares, unnecessary economic costs, loss of beneficial products, adoption of strategies with greater health costs, and the diversion of public funds into unnecessary research. An initiative to agree upon a standardized, internationally acceptable methodology for carcinogen assessment is needed now. The approach should incorporate principles and concepts of existing international consensus-based frameworks including the WHO IPCS mode of action framework.

Concepts: Chemical warfare, Benzene, Chemical Weapons Convention, Carcinogen, International Agency for Research on Cancer, Sulfur mustard, Risk, Decision making

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Radiofrequency radiation in the frequency range 30 kHz-300 GHz was evaluated to be Group 2B, i.e. ‘possibly’ carcinogenic to humans, by the International Agency for Research on Cancer (IARC) at WHO in May 2011. Among the evaluated devices were mobile and cordless phones, since they emit radiofrequency electromagnetic fields (RF-EMF). In addition to the brain, another organ, the thyroid gland, also receives high exposure. The incidence of thyroid cancer is increasing in many countries, especially the papillary type that is the most radiosensitive type.

Concepts: Cancer, Mobile phone, Cordless telephone, Ultraviolet, Ionizing radiation, X-ray, Carcinogen, International Agency for Research on Cancer

16

Circadian rhythms show universally a 24-h oscillation pattern in metabolic, physiological and behavioral functions of almost all species. This pattern is due to a fundamental adaptation to the rotation of Earth around its own axis. Molecular mechanisms of generation of circadian rhythms organize a biochemical network in suprachiasmatic nucleus and peripheral tissues, building cell autonomous clock pacemakers. Rhythmicity is observed in transcriptional expression of a wide range of clock-controlled genes that regulate a variety of normal cell functions, such as cell division and proliferation. Desynchrony of this rhythmicity seems to be implicated in several pathologic conditions, including tumorigenesis and progression of cancer. In 2007, the International Agency for Research on Cancer (IARC) categorized “shiftwork that involves circadian disruption [as] probably carcinogenic to humans” (Group 2A in the IARC classification system of carcinogenic potency of an agentagent) (Painting, Firefighting, and Shiftwork; IARC; 2007). This review discusses the potential relation between disruptions of normal circadian rhythms with genetic driving machinery of cancer. Elucidation of the role of clockwork disruption, such as exposure to light at night and sleep disruption, in cancer biology could be important in developing new targeted anticancer therapies, optimizing individualized chronotherapy and modifying lighting environment in workplaces or homes.

Concepts: International Agency for Research on Cancer, Cell, Genetics, Sleep, Circadian rhythms, Gene expression, Gene, DNA

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Recently, the International Agency for Research on Cancer issued a warning about the carcinogenicity of 1,2-dichloropropane (1,2-DCP) to humans based on an epidemiological study suggesting a relationship between the incidence of cholangiocarcinoma and occupational exposure to halogenated hydrocarbon solvent comprised mostly of 1,2-DCP. Although this dihaloalkane has been used in various industrial fields, there has been no biological evidence explaining the cholangiocarcinoma latency, as well as little understanding of general cholangiocarcinoma risk. In the present study, we explored the biliary excretion of 1,2-DCP metabolites by an untargeted metabolomics approach and the related molecular mechanism with in vitro and in vivo experiments. We hypothesized that the biliary excretion of carcinogens derived from 1,2-DCP contribute to the increased cholangiocarcinoma risk. We found that 1,2-DCP was conjugated with glutathione in the liver, and that the glutathione-conjugated forms of 1,2-DCP, including a potential carcinogen that contains a chloride atom, were excreted into bile by the bile canalicular membrane transporter, ABCC2. These results may reflect a risk in the backfiring of biliary excretion as a connatural detoxification systems for xenobiotics. Our findings would contribute to uncover the latent mechanism by which the chronic exposure to 1,2-DCP increases cholangiocarcinoma risk and future understanding of cholangiocarcinoma biology.

Concepts: Bile duct, Carcinogen, Metabolism, Liver, International Agency for Research on Cancer, Cancer, Benzene, Toxicology

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In October 26, 2015, the International Agency for Research on Cancer (IARC) issued a press release informing of the recent evaluation of the carcinogenicity of red and processed meat consumption. The consumption of red meat and processed meat was classified as “probably carcinogenic to humans”, and as “carcinogenic to humans”, respectively. The substances responsible of this potential carcinogenicity would be generated during meat processing, such as curing and smoking, or when meat is heated at high temperatures (N-nitroso-compounds, polycyclic aromatic hydrocarbons and heterocyclic aromatic amines). However, in its assessments, the IARC did not make any reference to the role that may pose some carcinogenic environmental pollutants, which are already present in raw or unprocessed meat. The potential role of a number of environmental chemical contaminants (toxic trace elements, polycyclic aromatic hydrocarbons, polychlorinated dibenzo-p-dioxins and dibenzofurans, polychlorinated biphenyls, polybrominated diphenyl ethers, polychlorinated diphenyl ethers, polychlorinated naphthalenes and perfluoroalkyl substances) on the carcinogenicity of consumption of meat and meat products is discussed in this paper. A case-study, Catalonia (Spain), is specifically assessed, while the influence of cooking on the concentrations of environmental pollutants is also reviewed. It is concluded that although certain cooking processes could modify the levels of chemical contaminants in food, the influence of cooking on the pollutant concentrations depends not only on the particular cooking process, but even more on their original contents in each specific food item. As most of these environmental pollutants are organic, cooking procedures that release or remove fat from the meat should tend to reduce the total concentrations of these contaminants in the cooked meat.

Concepts: Pollution, Soil contamination, Toxicology, Polycyclic aromatic hydrocarbon, International Agency for Research on Cancer, Meat, Polychlorinated biphenyl, Benzene

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The recent classification by International Agency for Research on Cancer (IARC) of the herbicide glyphosate as a probable human carcinogen has generated considerable discussion. The classification is at variance with evaluations of the carcinogenic potential of glyphosate by several national and international regulatory bodies. The basis for the IARC classification is examined under the assumptions that the IARC criteria are reasonable and that the body of scientific studies determined by IARC staff to be relevant to the evaluation of glyphosate by the Monograph Working Group is sufficiently complete. It is shown that the classification of glyphosate as a probable human carcinogen was the result of a flawed and incomplete summary of the experimental evidence evaluated by the Working Group. Rational and effective cancer prevention activities depend on scientifically sound and unbiased assessments of the carcinogenic potential of suspected agents. Implications of the erroneous classification of glyphosate with respect to the IARC Monograph Working Group deliberative process are discussed.

Concepts: Theory, Cancer, Evaluation, Research, Scientific method, Carcinogen, Science, International Agency for Research on Cancer

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The International Agency for Research on Cancer (IARC) classified diesel exhaust as carcinogenic to humans (Group 1) and gasoline exhaust as a possible carcinogen (Group 2B) based studies of lung cancer, however the evidence for other sites is limited. We addressed this question by investigating exposure to diesel and gasoline emissions with respect to risk of colorectal cancer in men.

Concepts: Internal combustion engine, Colorectal cancer, Lung cancer, Gasoline, Benzene, International Agency for Research on Cancer, Carcinogen, Cancer