PRESS RELEASE N° 208
31 May 2011
IARC CLASSIFIES RADIOFREQUENCY ELECTROMAGNETIC FIELDS AS
POSSIBLY CARCINOGENIC TO HUMANS
Lyon, France, May 31, 2011 The WHO/International Agency for Research on Cancer (IARC) has classified radiofrequency electromagnetic fields as possibly carcinogenic to humans (Group 2B), based on an increased risk for glioma, a malignant type of brain cancer1, associated with wireless phone use.
Over the last few years, there has been mounting concern about the possibility of adverse health effects resulting from exposure to radiofrequency elecromagnetic fields, such as those emitted by wireless communication devices. The number of mobile phone subscriptions is estimated at 5 billion globally
From May 24–31 2011, a Working Group of 31 scientists from 14 countries has been meeting at IARC in Lyon, France, to assess the potential carcinogenic hazards from exposure to radiofrequency electromagnetic fields. These assessments will be published as Volume 102 of the IARC Monographs, which will be the fifth volume in this series to focus on physical agents, after Volume 55 (Solar Radiation), Volume 75 and Volume 78 on ionizing radiation (Xrays, gammarays, neutrons, radionuclides), and Volume 80 on nonionizing radiation (extremely lowfrequency electromagnetic fields).
The IARC Monograph Working Group discussed the possibility that these exposures might induce longterm health effects, in particular an increased risk for cancer. This has relevance for public health, particularly for users of mobile phones, as the number of users is large and growing, particularly among young adults and children.
The IARC Monograph Working Group discussed and evaluated the available literature on the following exposure categories involving radiofrequency electromagnetic fields:
occupational exposures to radar and to microwaves;
environmental exposures associated with transmission of signals for radio, television
and wireless telecommunication; and
personal exposures associated with the use of wireless telephones.
International experts shared the complex task of tackling the exposure data, the studies of cancer in humans,
the studies of cancer in experimental animals, and the mechanistic and other relevant data
The evidence was reviewed critically, and overall evaluated as being limited2 among users of wireless telephones for
glioma and acoustic neuroma, and inadequate3 to draw conclusions for other types of cancers. The evidence from the
occupational and environmental exposures mentioned above was similarly judged inadequate. The Working Group did
not quantitate the risk; however, one study of past cell phone use (up to the year 2004), showed a 40% increased risk
for gliomas in the highest category of heavy users (reported average: 30 minutes per day over a 10year period).
Dr Jonathan Samet (University of Southern California, USA), overall Chairman of the Working Group, indicated that
"the evidence, while still accumulating, is strong enough to support a conclusion and the 2B classification. The conclusion means that there could be some risk, and therefore we need to keep a close watch for a link between
cell phones and cancer risk."
"Given the potential consequences for public health of this classification and findings," said IARC Director
Christopher Wild, "it is important that additional research be conducted into the longterm, heavy use of mobile phones. Pending the availability of such information, it is important to take pragmatic measures to reduce exposure such as handsfree devices or texting. "
The Working Group considered hundreds of scientific articles; the complete list will be published in the Monograph.
It is noteworthy to mention that several recent inpress scientific articles4 resulting from the Interphone study were made available to the working group shortly before it was due to convene, reflecting their acceptance for publication at that time, and were included in the evaluation.
A concise report summarizing the main conclusions of the IARC Working Group and the evaluations of the carcinogenic
hazard fromradiofrequency electromagnetic fields (including the use of mobile telephones) will be published in
The Lancet Oncology in its July 1 issue, and in a few days online.
1 237 913 new cases of brain cancers (all types combined) occurred around the world in 2008 (gliomas represent 2/3 of these).
Source: Globocan 2008
For more information, please contact
Dr Kurt Straif, IARC Monographs Section, at +33 472 738 511, or email@example.com;
Dr Robert Baan, IARC Monographs Section, at +33 472 738 659, or firstname.lastname@example.org; or
Nicolas Gaudin, IARC Communications Group, at email@example.com (+33 472 738 478)
Link to the audio file posted shortly after the briefing:
The International Agency for Research on Cancer (IARC) is part of the World Health Organization. Its mission is to
coordinate and conduct research on the causes of human cancer, the mechanisms of carcinogenesis, and to develop
scientific strategies for cancer control. The Agency is involved in both epidemiological and laboratory research and
disseminates scientific information through publicaions, meetings, courses, and fellowships.
Nicolas Gaudin, Ph.D.
Head, IARC Communications
International Agency for Research on Cancer
World Health Organization
150, cours AlbertThomas
69008 Lyon France
ABOUT THE IARC MONOGRAPHS
What are the IARC Monographs?
The IARC Monographs identify environmental factors that can increase the risk of human cancer. These include
chemicals, complex mixtures, occupational exposures, physical and biological agents, and lifestyle factors. National
health agencies use this information as scientific support for their actions to prevent exposure to potential carcinoens.
Interdisciplinary working groups of expert scientists review the published studies and evaluate the weight of the
evidence tha an agent can increase the risk of cancer. The principles, procedures, and scientific criteria that guide the
evaluations are described in the Preamble to the IARC Monographs.
Since 1971, more than 900 agents have been evaluated, of which approximately 400 have been identified as
carcinogenic or potentially carcinogenic to humans.
Group 1: The agent is carcinogenic to humans.
This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent may be
placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficent
evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent acts
through a relvant mechanism of carcinogenicity.
This category includes agents for which, at one extreme, the degree of evidence of carcinogenicity in humans is
almost sufficient, as well as those for which, at the other extreme, there are no human data but for which there is
evidence of carcinogenicity in experimental animals. Agents are assigned to either Group 2A (probably carcinogenic
to humans) or Group 2B (possibly carcinogenic to humans) on the basis of epidemiological and experimental evidence
of carcinogenicity and mechanistic and other relevant data. The terms probably carcinogenic and possibly carcinogenic
have no quantitative significance and are used simply as descriptorsof different levels of evidence of human
carcinogenicity, with probably carcinogenic signifying a higher level of evidence than possibly carcinogenic.
Group 2A: The agent is probably carcinogenic to humans.
This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of
carcinogenicity inexperimental animals. In some cases, an agent may be classified in this category when there
is inadequate evidence of carcinogenicity in humans and sufficient evidnce of carcinogenicity in experimental
animals and strong evidence that the carcinogenesis is mediated by a mechanism that alsooperates in humans.
Exceptionally, an agent may be classified in this category solely on the basis of limited evidence of carcinogenicity
in humans. An agent may be assigned to this category if it clearly belongs, based on mechanistic considerations, to a
class of agents for which one or more members have been classified in Group 1 or Group 2A.
Group 2B: The agent is possibly carcinogenic to humans.
This category is used for agents for which there is limited evidence of carcinogenicity in humans and less than
sufficient evidnce of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence
of carcinogenicity in humans but there is sufficient evidence of carcinoenicity in experimental animals. In some
instances, an agent for which there is inadequate evidence of carcinogenicity in humans and less than sufficient
evidence of carcinogenicty in experimental animals together with supporting evidence from mechanistic and other
relevant data may be placed in this grop. An agent may be classified in this category solely on the basis of strong
evidence from mechanistic and other relevant data.
Group 3: The agent is not classifiable as to its carcinogenicity to humans.
This category is used most commonly for agents for which the evidence of carcinogenicity is inadequate in humans
and inadequateor limited in experimental animals.
Exceptionally, agents for which the evidence of carcinogenicity is inadequate in humans but sufficient in experimental
animals may be placed n this category when there is strong evidence that the mechanism of carcinogenicity in experimental animals does not operate in humans.
Agents that do not fall into any other group are also placed in this category.
An evaluation in Group 3 is not a determination of noncarcinogenicity or overall safety. It often means that further research is needed, especially when exposures are widespread or the cancer data are consistent with differing interpretations.
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This category is used for agents for which there is evidence suggesting lack of carcinogenicity in humans and in
experimental aimals. In some instances, agents for which there is inadequate evidence of carcinogenicity in humans
but evidence suggesting lack of carcinogenicity in xperimental animals, consistently and strongly supported by a
broad range of mechanistic and other relevant data, may be classified in this group.
Definitions of evidence, as used in IARC Monographs for studies in humans
The evidence relevant to carcinogenicity from studies in humans is classified into one of the following categories:
Sufficient evidence of carcinogenicity: The Working Group considers that a causal relationship has been established between exposure to the agent and human cancer. That is, a positive relationship has been observed between the exposure and cancer in studies in which chance, bias and confounding could be ruled out with reasonable confidence.
A statement that there is sufficient evidence is followed by a separate sentence that identifies the target organ(s) or tissue(s) where an increased risk of cancer was observed in humans. Identification of a specific target organ or tissue does not preclude the possibility that the agent may cause cancer at othersites.
Limited evidence of carcinogenicity: A positive association has been observed between exposure to the agent and cancer for which a causal interpretation is consideed by the Working Group to be credible, but chance, bias or confounding could not be ruled out with reasonable confidence.
Inadequate evidence of carcinogenicity: The available studies are of insufficient quality, consistency or statistical power to permit a conclusion regarding the presence or absence of a causal association between expoure and cancer, or no data on cancer in humans are available.
Evidence suggesting lack of carcinogenicity: There are several adequate studies covering the full range of levels of exposure that humans are known to encounter, which are mutually consistent in not showing a positive association between exposure to the agent and any studied cancer at an observed level of exposure. The results from these studies alone or combined should have narrow confidence intervals with an upper limit close to the nullvalue (e.g. a relative risk of 1.0). Bias and confounding should be ruled out with reasonable confidence, and the studies should have an adequate length of follow up. A conclusion of evidence suggesting lack of carcinogenicity is inevitably limited to the cancer sites, conditions and levels of exposure, and length of observation covered by the available studies. In addition, the possibility of a very small risk at the levels of exposure studied can never be excluded.
In some instances, the above categories may be used to classify the degree of evidence related to carcinogenicity in specific organs or tissues.
- Red de Institutos Nacionales de Cancer de Latinoamérica RINC-ALC - 26th June 2019
- Pioneers in Infectious Agents and Cancer Meeting - 2nd March 2017
- IARC 50th Anniversary Meeting 2016 - 13th June 2016
Defeating cancer with antidepressants
Julian Lieb, M.D
Prostaglandins are ephemeral, infinitesimal signalers self-regulating every cell in the body, including those sub-serving mood and immunity. At first, they were perceived as a master switch, but now are believed to regulate every component of cellular micro-anatomy and physiology, including those of the organelles, cytoskeleton, proteins, enzymes, nucleic acids and mitochondria. Prostaglandins are responsible, paradoxically, for cell function and dysfunction. Excessive prostaglandin synthesis depresses immune function and may induce cancer. An ideal anti-cancer agent would inhibit prostaglandins in such a manner as to shut down the pathogenesis of cancer. In this paper, I will show that antidepressants have such properties.
The anti-prostaglandin, immunostimulating and antimicrobial properties of lithium and antidepressants
Depression predisposes us to, among other things, infection, cancer, osteoporosis, and neurodegenerative, cardiovascular and auto-immune disorders [1,2]. Excessive syntheses of prostaglandins is incriminated in all of these [1,2]. Lithium and antidepressants have potent anti-prostaglandin, immunostimulating and antimicrobial properties, and antidepressants have the paradoxical ability to mitigate, reverse or induce auto-immunity [1,2].
When synthesized excessively, prostaglandin E2 depresses cellular and humoral immunity, allowing pathogens to replicate 3. Prostaglandins regulate the physiology, immunity, replication and toxicity of micro-organisms and the resistance of their hosts [1–4]. Failure of non-steroidal anti-inflammatory drugs in infections led to the conclusion that inhibiting prostaglandins has limited value in that field. The prostaglandin-inhibiting properties of lithium and antidepressants have been neglected [5–10], along with their unique immunopotentiating and antimicrobial actions . In the early 1950s, clinicians observed that patients treated for tuberculosis with the monoamine oxidase inhibitors isoniazid and iproniazid had an elevation of mood and energy. It was also observed that monoamine oxidase inhibitors have dual anti-tuberculosis and antidepressant properties failed to impact the pharmacology of infectious disorders. Remission of such manifestations of viral infections as sinusitis, sinobronchitis, frequent colds, sore throats, cold sores and genital herpes in patients taking lithium carbonate has been reported [11–13]. The polymorphonuclear leukocytes of a 29-year-old woman with eczema and recurrent staphylococcal and streptococcal skin infections were unresponsive to standard chemotactic stimuli. In vitro addition of lithium to her polymorphonuclear preparations restored their chemotactic response. After receiving lithium carbonate, 1 g/d for five weeks, she became free of infection and relapsed when lithium was withdrawn . Lithium chloride prevents replication of type 1 and 2 herpes virus in cell culture  and augments several in vitro immune reactions .
Monoamine oxidase inhibitors can reverse tuberculosis, aphthous ulcers, cold sores, genital herpes, upper respiratory tract infections and plantar warts [17–19]. Tricyclic antidepressants can reverse aphthous ulcers , reduce the frequency of recurrences of shingles [1,2], remit the pain of this disorder [1,2], prevent post-herpetic neuralgia [1,2], destroy leishmania minor and major in vitro , and inhibit in vitro growth of the intestinal parasite giardia lamblia . Tricyclic antidepressants have anti-malarial properties: they enhance in vitro susceptibility of Plasmodium falciparum to chloroquine and are lethal in vitro against Trypanasoma parasites [23-27]. Selective serotonin re-uptake inhibitors can destroy such fungi in vitro as Candida and Aspergillus , reverse recurrent vulvovaginal candidiasis in vivo , have anti-microbial activity  and are synergistic when combined with antibiotics .
Impaired lymphocyte function reduced natural killer cell activity, reduced lymphocyte responses to mitogens and decreased natural killer cell populations have been demonstrated in depressives [1,2,32,33]. Tricyclic antidepressants augment natural killer cell activity in vivo and in vitro  and the monoamine oxidase inhibitor tranylcypromine enhances defective cell-mediated immunity . As lithium and antidepressants have immunopotentiating properties, they are effective against a wide range of micro-organisms. Evidence to date shows that while lithium has antiviral and antibacterial properties, antidepressants have antiviral, antibacterial, antiparasitic and fungicidal properties. Response of infection to lithium and antidepressants mirrors that of response to depression, with subjects responding selectively to antidepressants or lithium; antidepressants are highly specific and humans remarkably variable. Response of depression and infection to lithium or an antidepressant is usually simultaneous, suggesting that the central actions of the drugs are important. While antivirals are not necessarily immunostimulants, lithium and antidepressants are invariably antivirals. If antidepressants double as antibiotics, it would not be surprising if antibiotics doubled as antidepressants. Many antibiotics, among them clarithromycin, erythromycin, amoxacillin and ciprofloxacin, can elevate mood to the level of hypomania or mania .
Prostaglandins in carcinogenesis
Among the mechanisms of carcinogenesis are up-regulation of cyclooxygenase, oncogene synthesis and expression, viral activation, signal disruption, accelerated cell replication, failed apoptosis, tumor initiation and promotion, angiogenesis, metastasis, immunosuppression, auto-immunity and activation of mitochondria. All fall within the orbit of prostaglandins and their forming enzymes. In 1968, Williams reported high levels of prostaglandins in the thyroid and plasma of patients with medullary cancer of the thyroid . In 1976, Goodwin reported excessive synthesis of prostaglandin E2 in suppressor T-cells of patients with Hodgkin’s disease . Numerous studies have confirmed elevated levels of prostaglandins in solid tumors and in the immune cells and body fluids of cancer patients [39,40]. The isolation of such isoforms of cyclooxygenase as COX-2 , and the synthesis of selective COX-2 inhibitors has stimulated research into the expression of this isoform in cancer and its role in apoptosis. COX-2 is up-regulated in such cancers as those of the head and neck, breast, lung, pancreas, bladder, cervix, prostate and mesothelium [41–43]. In population studies, chronic use of such prostaglandin inhibitors as aspirin and ibuprofen has reduced the risk of colon cancer by as much as 40% .
Armato and Andreis showed that arachidonic acid and prostaglandins F1 alpha and F2 alpha stimulate the DNA-synthetic and mitotic activities of hepatocytes . Goodlad has reported that the increase in gastric mucosal mass induced by misoprostol in the stomach of dogs is due to increased cell production. The increase in mucosal mass was the result of a dramatic increase in the foveolar surface mucous cells , other studies show a paradoxical, inhibitory effect of prostaglandins on DNA synthesis . Prostaglandins and their synthesizing enzymes are key factors in many signaling events, and disruptions of signaling pathways have been incriminated in many cancers.
In her pioneering studies, Karmali [48,49] showed that increased thromboxane formation in human breast cancer specimens is associated with three clinical variables: tumor size, axillary lymph node metastases and distant metastases. The mechanisms by which prostaglandins and thromboxanes induce metastasis include induction of proteolytic enzyme production, neovascularization and subversion of the immune response. The initiation of metastasis is thought to involve the adherence of circulating tumor cells to endothelial cells or to basement membranes. Prostaglandins and thromboxanes play a role in adherence [49,50], with local thromboxane concentrations possibly determining the sites of metastasis . Immunosuppression is a cause and effect of cancer. Increase in prostaglandins at the primary tumor focus may block surveillance by the immune system, while an increase in plasma prostaglandins may contribute to the suppressive environment for lymphocyte function .
In a paradoxical counterpoint to immunosuppression, numerous autoimmune phenomena are reported in patients with cancer . Malignant tumors are diagnosed with increased frequency in patients with such autoimmune disorders as pemphigus, Myasthenia gravis and the Eaton-Lambert syndrome [54,55]. The paraneoplastic syndrome includes a variety of neurological, hematological, metabolic, cardiovascular and dermatological disorders, in all of which prostaglandins have been incriminated [55,56]. As monoamine oxidase inhibitors, originally used in the treatment of tuberculosis, have potent antiviral and immunostimulating properties, it is not surprising that one of them, Matulane (procarbazine), is effective in treating stage 111 and 1V Hodgkin’s disease.
Depression: A precursor of cancer
In the Ward Jones lecture given at Manchester University in 1957, Sir Heneage Ogilvie commented, ‘I have slowly come to frame in my mind an aphorism that can never be stated as such, because no statistics can be advanced to support it: “The happy man never gets cancer” … The instances where the first recognizable onset of cancer has followed almost immediately on some disaster, bereavement, the breakup of a relationship, a financial crisis, or an accident are so numerous that they suggest that some controlling force that has hitherto kept the outbreak … in check has been removed’ . In 1998, Penninx et al at the National Institute of Aging provided compelling data for Ogilvie’s hypothesis: chronically depressed people over the age of 70 are 88% more likely to develop cancer and twice more likely to die of it than their mellow peers .
Antineoplastic properties of antidepressants in vitro
Many studies show that antidepressants have potent anti-cancer properties, both in vitro and in vivo, with regard to various antidepressants, mechanisms of action and cancer cell types [59–78]. Irrespective of their putative mechanism of action, the antidepressants destroyed the cells or arrested their proliferation [59–78]. Hydroxyprostaglandin dehydrogenase is the primary prostaglandin-degrading enzyme, highly expressed in normal colon mucosa but lost in human colon cancers [79,80]. Lack of this enzyme promotes the earliest steps of growth of benign as well as malignant colon tumors [79,80]. When this enzyme was first characterized, every agent tested in the hope of stimulating it either had no effect or inhibited it. Eventually Mak and Chen showed that amitriptyline and imipramine powerfully activate the enzyme in mice, especially the kidney enzyme, with more than a thousand-fold activation by amitriptyline. Amitriptyline and imipramine had potent activating effects on this enzyme in the brain .
Mitochondria, prostaglandins and antidepressants
Mitochondria are tiny organelles that supply cellular energy and are involved in signaling, cellular differentiation, control of the cell cycle, growth and programmed cell death. The cells of malignant gliomas of the brain, and small and non-small cell cancers of the lung, tend to repair DNA-breaks caused by radiation and chemotherapy. In an effort to accomplish cell death by an alternative method, investigators are targeting mitochondria. Small molecule agents known as ‘mitocans’ are able to enter tumor cell mitochondria, reduce oxygen consumption, and activate mechanisms leading to cell death. Agents that can destroy cancer cells in this manner, while leaving normal cells intact, notably include antidepressants [82-84]. Laboratory experiments using this approach on various cancer cells, including those of gliomas, are encouraging [65,66]. It goes without saying that prostaglandins are intermediaries between mitocans and mitochondria [85–87].
Antineoplastic properties of antidepressants in vivo
A woman suffering from major depression and advanced liver cancer (hepatoma) was treated with psychotherapy, the antidepressant fluvoxamine (Luvox), glycyrrhizin acid and dehydroepiandrosterone (DHEA). Various indices of defective immune function normalized, and her liver function tests improved. At follow-up two-and-a-half years later, she was well and symptom free . In 1990, a 60-year-old woman had a mastectomy for inflammatory breast cancer, followed by excision of infiltration of the chest wall. She was given a prognosis of less than a year. I treated her with various antidepressants, and when relocating in 2003 she was in apparent good health.
Antidepressants have the potential to arrest, prevent, reverse and palliate cancer. Short of that they have many other uses in cancer care. Antidepressants can reduce the severity and frequency of hot flashes in patients treated with chemotherapy for breast cancer, and remit acute neurosensory symptoms secondary to oxaliplatin chemotherapy . The monoamine oxidase inhibitors deprenyl and clorgyline protect nonmalignant human cells from ionizing radiation and chemotherapy toxicity , and antidepressants are capable of reversing chemotherapy-induced vomiting .
As the response to antidepressants is highly specific, many patients require multiple trials before responding. Some subjects are refractory to all antidepressants, and some relapse due to tachyphylaxis . Prostaglandins are capable of paradoxically inducing pro- and anti-cancer actions. The omnipresence of paradox warns that antidepressants are capable of initiating or accelerating cancer. Maintaining an index of suspicion, close clinical observation and limiting the duration of drug trials can mitigate such paradox. Epidemiological studies have failed to confirm the suspicion that antidepressants may induce breast cancer . However, breast cancer has been reported in three men, taking selective serotonin re-uptake inhibitors .
Wherever prostaglandin-synthesizing enzymes convert arachidonic acid or phospholipids to prostaglandins, there are possible sites of action of antidepressants. By maintaining these enzymes within physiological limits, antidepressants shut down the mechanisms of carcinogenesis. Considerable evidence now shows that antidepressants are cytotoxic and cytostatic; convert multidrug resistant cells to sensitive and protect nonmalignant cells from ionizing radiation and chemotherapy . While lithium has immunostimulating and anti-microbial properties, there is little evidence for its possible antineoplastic actions. Antidepressants have potent analgesic properties alone or as potentiators of narcotics, and they enhance sleep, appetite and occasionally energy. Their immunostimulating and anti-microbial properties are relevant to infection secondary to chemotherapy or radiation. Alleviation of anxiety, depression, fear of death,
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Good article! That what we are believing.
Jagadeesh S Rao PhD
Signal Transduction Unit
Brain Physiology and Metabolism Section National Institute on Aging
NIH 9000, Rockville Pike Building 9, Room 1S-126 Bethesda MD 20892
From: Julian Lieb M.D. [mailto:firstname.lastname@example.org]
Sent: Thursday, September 08, 2011 9:52 AM
To: Rao, Jagadeesh (NIH/NIA/IRP) [E]
Subject: Resisted paradigm shift
Retired, Yale medical school professor
48 articles, 12 books
All antidepressants are immunostimulating and anticancer agents. Significant variation in matching antidepressant to subject.
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Have only just read this and am sorry to learn of Dr Bui’s passing. I worked with him at UN CICRED in Paris from 1974 to 1984 and greatly appreciated his kindness.