proof required

Micah Barchana, the cancer registrar at the Ministry of Health reassures those who fear that cellular radiation causes cancer

Micah Barchana Galileo

Proving a causal relationship is a rather complex matter in the field of modern medicine, since such a proof must be based on previous knowledge, which itself is in a state of daily renewal and updating, and cross many bumps related to the fact that most known diseases have many causes. In addition to the relative contribution of each individual factor to the development of a disease, there is sometimes a pattern or overlap of the factors.

Moreover, even though we tend to treat human biology as a constant and universal fact, science today distinguishes, albeit partially and imperfectly, between different people in relation to the degree to which they are affected by certain factors, a fact that is at the basis of the growing trend in the world of "personalized medicine".

Already today, in an increasing part of treatments for various cancer diseases, various personal factors (receptors, hormones) are tested that predict the chances of success of various treatments; Depending on their presence, the therapeutic approach is determined.

Diseases: cause and effect

In the older world, where infectious diseases still dominated, Robert Koch (Koch) proposed in 1890 some assumptions for determining the causal relationship between microbial pollutants (Koch specifically referred to anthrax - anthrax, and tuberculosis) and morbidity. In order to confirm such a connection, Koch stated that the same pathogen must be present in the body of the sick person, but not in a healthy person; that the agent can be isolated from the patient's body and grown under laboratory conditions; that the pathogen will cause the symptoms of the disease if introduced into a healthy body; And after it gets sick, it will be possible to isolate the cause from the patient's body and grow it again under laboratory conditions and it will be the same cause.

The first assumption (that the causative agent will only be found in a sick person) was later abandoned, when it was clarified that there is a possibility of carrying a causative agent without an active disease, and it was clarified that one such causative agent may cause several diseases with different symptoms. These assumptions (known as "Koch's postulates") are only partly accepted in modern medicine, where there are not only two dimensions - the cause of a disease and the patient, but rather the number of actors related to the formation of a disease is large.

About a decade after the discovery of penicillin in 1928 (and other antibacterial drugs in 1932) these drugs were widely used, and because of this there was a decline in mortality from infectious diseases, and the scientific world was freed to deal with morbidity from other causes. One of the main effects of the use of antibiotic drugs was a considerable increase in life span.

In 1900, the average life expectancy was 31 years, and in the 50s it was 66 years (while at the beginning of the 80s, on a global average, the life expectancy is XNUMX years and in some countries it reaches XNUMX years or more). As a result, interest in non-infectious diseases increased at the expense of infectious ones .

At the same time, the development of industry and with it the environmental pollution and the changes in the working habits of the population, which moved from mainly physical work to more stationary work, on the side of machines and production lines, led to an increased interest in respiratory, cardiovascular and later malignant diseases (cancer).

Working near the production lines brought with it new diseases. Illustration: ingimage

Finding causality
Finding causality and proving it in these diseases seemed from the beginning to be more complex tasks, and as the research progressed the understanding that it was not only a direct relationship between one cause and one result. In this context, the biostatistician Bradford Hill (Hill) published an article in 1965 called "Environment and Disease: Connection or Causality?". Hill, who later received the title "Sir", insisted on the difficulties in determining causality for diseases and proposed some rules for examining the proof of causality.

The milestones proposed by Sir Hill are accepted to this day as a tool for examining the causation of diseases. As he himself pointed out, these rules are not binding rules in every situation, and the existence or absence of some of them does nothing to confirm or rule out such a connection (except for one rule that refers to the schedule, since the exposure to the cause must always precede the result - the symptoms of the disease). Drawing conclusions, in light of those points, remains, therefore, in the hands of scientists.

The rules established by Sir Hill are accepted even today, and are used by researchers when they come to establish a causal relationship between different phenomena. Therefore, in this article I will try to follow those milestones, one by one, while examining the question of a possible causal relationship between non-ionizing radiation of radio waves (electromagnetic radiation, EMF) from mobile (cellular) phones and various cancers.

I will start by saying that the LMWH radiation has accompanied the development of the human race for over 100 years, since Marconi (or his competitors) began experiments in 1895 by sending radio transmissions over distances that today are considered very short. This radiation has fully accompanied our lives for decades, starting with radio and television transmissions , communication between planes and ships, army and various rescue agencies, continued with transmissions between various commercial entities, and ended with transmissions at the level of the neighborhood pizza delivery and a local delivery company.

Two touchstones

The meteoric rise in the use of mobile radio-telephone devices (RATN) in Israel began in 1994 when 3.5% of the population in Israel had these devices. At the end of six years, 100% of the adult population had at least one Ratan device: data from recent years indicate that every citizen aged 15 and older has about 1.4 devices.

All of these have raised concerns about negative health effects that may be related to radiation. The basis for the concern is to a large extent a connection (and perhaps: a failure) to the language - the expression "radiation", since the general public knows the consequences of "radiation" in the context of various cancers, such as due to the dropping of the nuclear bombs in Hiroshima and Nagasaki and in the context of the accident in the nuclear reactor in Chernobyl.

It is important to note and emphasize that between these nuclear events and radiation from RTN devices there is nothing and half nothing, since in the nuclear cases we are dealing with ionizing radiation, which is completely different from LMG radiation, but in the mind of the general public, who is not necessarily aware of the differences, a connection is created, as mentioned automatic" between radiation and cancer.

Therefore, we will try to examine what is known today about the relationship between the use of rattan and malignant diseases (cancer), and this in light of the same milestones that Sir Hill proposed. We will also point out that the use of Ratan began worldwide (and even in Israel to a lesser extent) in the late XNUMXs, and therefore the common claim that "not enough time has yet passed" to examine those connections is not acceptable in our eyes.

1. The strength of the relationship
The strength of the relationship (strength): The strength of the relationship (between a factor and the outcome) describes the morbidity in the population exposed to the factor compared to a population not exposed to it. For example, if we follow a population of smokers for several decades and a similar population that does not smoke for a similar period of time and compare the number of lung cancer patients in each of the groups, then we can quantify the strength of the relationship between the cause (smoking) and the morbidity. It is clear to us that lung cancer patients will also be found among non-smokers, but assuming that the proportion of patients among smokers will be higher, we can, in a simple way, quantify the strength of the relationship between smoking and lung cancer morbidity.

The intensity is usually expressed in percentages: among smokers the morbidity is 400% higher (say, 4 times) than among non-smokers. This ratio expresses the strength of the relationship (4 times). When dealing with cancer, it is rare to find situations where the strength of the connection between a carcinogen and morbidity are at such levels. Usually, such relationships are measured in single or tens of percents (such as, for example, the use of hormonal replacements for menopausal women, which increase the risk of breast cancer by 20-15%).

On the same weight we can find opposite relationships, also in different strengths. For example, use of birth control pills and ovarian cancer. In many studies, it was found that in women who use birth control pills, the risk of ovarian cancer decreases by 20-10% after one year of use and it decreases to 50% after five years of using the pills. Numerically (in percentages), this means that women who use the pill have an 80% risk (or a ratio of 0.8) in relation to the population of women who do not use the pill to develop ovarian cancer after one year of use and a 50% risk after five years of use.

It is customary to call such a factor a "protective factor", since the use of pills is a protective factor (in varying strength depending on the duration of use) against ovarian cancer. The interpretation of the relationship strength index is intuitive and self-evident: the greater the strength, the stronger the relationship between the cause and morbidity (whether as a risk factor or as a protective factor).

In the field of cell phones, several studies were conducted in which the researchers examined the strength of the relationship between malignant diseases of the brain (mainly) and the salivary glands (located in the area of ​​the jaws) and the use of X-ray devices. I would like to point out that for practical reasons (the duration of the research and its costs as well as ethical considerations) the studies are all based on patients with these diseases compared to a population group that is not sick, and the duration of use of X-ray devices (the duration of exposure) is examined.

This research method, a case-control study, entails several difficult methodological problems, the main one of which is memory bias: the reader of the article will now be asked to try to recall how many hours per month he used his mobile phone four years ago, what device he had in his hands, how many of those hours he used In the car speaker or in the headset and some of them in the right ear and some in the left ear.

Most users find it very difficult to answer these questions, as these details are not of interest to us. In many studies it has been found that if a person who has a disease is asked the same questions, and especially if it is a disease that may be related to the same factor, then the memory mechanisms work differently, and the person asked will "remember" the variables themselves in a different way.

The interphone study
The study with the largest number of participants conducted so far is called "Interphone", in which 5,117 patients with the two most common types of brain malignancies (gliomas and meningiomas) and double the number of control subjects (with the necessary adjustments such as age and gender) who are not patients, were asked about the use of X-ray devices. The results of the study indicated that the crossover ratio (an expression describing the "relative risk" in case/control studies) was 81% among glioma patients (a malignant tumor originating from the tissue that surrounds the nerve cells) and 79% among meningioma patients (a tumor - benign or Malignant – of the meninges).

The researchers note that no cross-ratio higher than 100% was found for users over ten years: the cross-ratio was 98% for gliomas and 83% for meningiomas. The researchers concluded that no increased risk of gliomas or meningiomas was found in connection with mobile phone use.

As explained earlier, when the risk of morbidity in the exposed group is lower than that in the control group, then the factor is considered a "protective factor". Indeed, the results of this study clearly indicate that the use of cell phones is a protective factor (of about 20%) against the two common types of brain tumors. It is clear that in the prevailing atmosphere the authors did not dare to call their findings a protective factor, but from a research point of view the findings do indicate this.

Hence, the first milestone in which the question was examined indicates that the use of X-ray devices does not have sufficient strength to indicate a relationship between cancer morbidity and the use of the devices, but rather the opposite: although there is a relationship between use and morbidity, it is an "inverse relationship", i.e. Increased use is associated with less morbidity.

2. consistency
Consistency: The meaning of this touchstone is that the same morbidity factor is consistently found to be associated with the outcome (disease) in different studies, done by different researchers, and with different research methods. Let's take as an example the relationship between tobacco use (smoking) and breast cancer. For years, researchers have been trying to find out if there is a connection between breast cancer and smoking.

It is possible to find in the medical literature quite a number of articles describing studies in which such a relationship was found, as well as a similar number of studies that did not find such a relationship. Hence, there is no consistency in the findings that try to link these two phenomena as a causal factor, and because of this, there is, as of today, no broad agreement among the experts regarding such a link, and therefore the use of tobacco and its products is not considered a risk factor for breast cancer today.

This touchstone exhausts the scientific method of establishing a causal relationship in that not every "new study" establishes a clear rule in the field, and that it is necessary to repeat findings in order to conclude that a relationship does exist. The need for this touchstone is mainly due to the fact that each research method has advantages and disadvantages, in any research there may be unintended errors and therefore it is necessary to substantiate the evidence in order to establish a causal relationship.

In the context of exposure to LMG radiation from RTN devices, the results of several dozen studies have been published to date. Of those that refer to radiation from stationary transmission centers (antennas) and of those that refer to the exposure of patients with brain tumors. The finding of a lower rate of brain tumors among users is found in several studies, and not only in the study cited earlier (although the researchers note that in their opinion a "protective effect" is unlikely and therefore do not discuss it at all).

The researchers try to explain the strange findings in a variety of ways, including sampling errors, a low participation rate in the study, early symptoms of brain tumors that prevented people from using mobile phones, and other factors. I will only note that during the research those researchers published articles justifying the research method they used and indicated that the fear of these research errors is extremely low.

It is important to note that one or another single finding from a study laden with problems and biases cannot be admissible, since if there are biases (and so many biases), it is not possible for a single finding to be free of biases.

Pursuit of evidence
One of the methods used by researchers extremes the "pursuit" of evidence for the existence of such a connection; This is a case-control study of the use of cell phones and morbidity among dead people (!) the problem that the study participants found it a little difficult to answer questionnaires about the use they made (while they were alive, apparently) of phones, the researchers solved by asking their relatives (try to imagine what these answered in the case of death from a brain tumor).

The results of this study showed that there was a 2.4 times risk of brain tumor among users who died of a brain tumor. In this context, it should be noted that there are real failures in attempts to establish such a relationship: there is no real and accurate quantification of the exposures themselves. Since there is no research basis or a clear assumption of the mechanism by which radiation can cause cancer, there is no possibility of confirmation. The third problem is the relatively large variety of results (different brain tumors) that may be related to radiation and thus in the absence of a clear result it is more difficult to establish a connection between the exposure and the result
.
The direction of my research in the last few months is the examination of morbidity trends in brain tumors in connection with the frequency of the use of X-ray devices. Several studies have already been published in this context and the summary of their findings is also inconclusive: in most of them no correlation was found between an increase in the incidence of tumors corresponding to the use of mobile phones (Inskip and colleagues; Delator and colleagues), while in other studies such a correlation was found (Lerer and colleagues).

3. specificity
Specificity: The specificity criterion emphasizes the relationship between the cause and the result (the carcinogen and the target organ it affects). In the general public there is a widespread opinion that a carcinogen can cause "any cancer", but this is not the case. An example of this is exposure to asbestos fibers, which can cause cancer of the lung membrane (pleura), cancer of the abdominal membrane (peritoneum, peritoneum) and more rarely also lung cancer. There is no evidence that exposure to asbestos can cause another malignancy.

Specificity also applies to the ways of exposure, so exposure to cadmium, in order to be a cause of cancer, must be respiratory exposure (as opposed to skin contact or ingestion) and this exposure may cause lung cancer only (although there are claims, which are not well-founded, of a link with prostate cancer) . The same goes for ionizing radiation, whose target organs are more numerous but still limited in scope (brain tumors, thyroid gland, lung, blood cancer, breast, colon and kidney) or exposure to electromagnetic fields suspected of causing leukemia in children only (when the emphasis is on leukemia only and only in children) .

Hence, the "multiplicity of results" in the context of LMG radiation (different types of tumors and in different organs) is improbable both for the reason that the results of the studies indicate the absence of such a relationship and also for the reason that no specificity is revealed in this case. We will also note that the International Agency for Research on Cancer (IARC), a body of the World Health Organization, in its determination in June 2011 that radiation from cell phones may be linked to cancer, refers only to tumors of the glioma type (in the brain) and not to any other type of tumor.

The resulting media uproar in Israel resulted, unfortunately, in the dissemination of incorrect data and irrelevant "proofs" (such as statements that this announcement proves a link to salivary gland tumors).

4. hierarchy
Gradient (dose-response relationship, Gradient): Another layer that supports proving a causal relationship is a dose-response relationship. This relationship exists and is known for tobacco (smoking), so that the risk of lung cancer, for example, for those who smoke a larger amount, is greater compared to the risk of those who smoke a smaller amount. The same goes for the risk of esophageal or liver cancer in relation to alcohol consumption or the use of certain medications. In the current case, proof is required that those who use cell phones more are at an increased risk of cancer, and this in a monotonous way.

The findings of the interphone study that we have already discussed do not indicate such a relationship, since at all levels of use the risk of brain malignancies was lower among the users, regardless of the time or duration of use; Only in one subgroup did it seem as if those who used the mobile phone a lot were at increased risk. Since this finding is not supported by any dose-response curve, the authors of the study claimed that this finding is not significant at all, and certainly does not meet this important rule.

5. Time connection
Temporality: Among all the tests proposed by Sir Bradford Hill, the only one that is considered necessary to prove a causal relationship is the test of temporality. There is a clear requirement that the exposure precedes the result, and in the field of malignant diseases this requirement is even more emphasized, since there is a latency period between the exposure and the diagnosis of the disease. That is, the exposure can be very early, while the clinical diagnosis of the cancerous disease is much later, and throughout the latency period the cancerous process is present in the background, but with the existing diagnostic means it is not possible to detect it.

By this issue are meant those who claim that "not enough time has passed" since the beginning of the use of cell phones to give full expression to the morbidity that may be related to it. We note that when it comes to ionizing radiation, the latency time for malignancies in the thyroid gland and the circulatory system is about two years, depending on the amount of exposure, and the average time for clinical manifestation of most cancerous tumors is about ten years. If radio wave radiation had the ability to cause malignant changes in cells similar to ionizing radiation, since the use of this technology in the wider world (and even in Israel) has been going on for years, we should have seen at least the "tip of the iceberg" of the expected excess morbidity.

However, studies published in recent months indicate that the incidence of malignant brain tumors with a low level of violence has actually been decreasing in recent decades and that the incidence of more violent brain tumors, which has been on the rise since the seventies, continues to increase at a lower rate than in the past.

6. Additional criteria
Additional criteria: Another important rule in examining a possible causal relationship between the use of cell phones and the risk of cancer is the biological gradient & plausibility. It is a change in DNA, the cellular genetic material, that underlies the cancer process and is responsible for the uncontrolled cell divisions and the additional phenomena that characterize malignant tumors.

Biological feasibility means the ability to propose a biological mechanism acceptable and adapted to what is known so far, which would explain how LMG radiation is able to cause this type of damage. So far, despite many different attempts made in tissue cultures and laboratory animals, it has not been proven that LMWH radiation is able to cause cellular damage that could be translated into the beginning of a cancerous process.

Only recently has it been reported that LMG radiation affects the local blood circulation in the exposed area and that an increase in sugar consumption was observed in this area. That is, there is a local effect (within a range of 4-3 cm from the radiating device). But the meaning of these findings is not clear: on the one hand, it may indeed be "proof of damage", but on the other hand, it may actually be proof of encouraging factors that repair cellular damage, which may have existed before; Because in every case of damage to a living cell, different cells are "called in" to repair the damage and/or destroy the damaged cell.

There are studies that indicated a reduction in the rate of tumors with a low potential for violence in comparison to an increase in the rate of use of mobile phones, perhaps implying that the second explanation is the more likely (and especially when so far there is no evidence of causing damage at the cellular level due to exposure to radio radiation).

Summary
In conclusion, in this article I tried to systematically follow the accepted rules in the world of medical science for decades regarding proving a causal relationship between some factor and a health outcome. These rules were used in establishing a causal relationship between certain risk factors and cancer, and they are still used by researchers and health institutions around the world.

From examining the rules one by one, I was not convinced that at this stage there is indeed a well-founded research hold for the fear that there is a connection between exposure to radio radiation from mobile phones and any malignant diseases, both on the basis of the absence of a biological mechanism of causing damage and on the basis of the studies of the various populations. The recent statement made by the Agency for Cancer Research, that EMG radiation from mobile phones is classified in category IIb of human carcinogens (as well as drinking coffee and eating pickles), stems more from the desire to emphasize the principle of preventive precaution and less from being based on real findings in the field, at least according to all that is known So far.

And a final note: a study, the largest of its kind to date, was recently published in the professional press, which included approximately four million person-years and 18 years of monitoring groups of mobile phone users and those who do not use them. In examining users over 10 or 13 years of age, no excess morbidity was found and no basis for a dose-response effect was found in the context of the two main types of brain malignancies (gliomas and meningiomas). The advantage of the study, beyond its size and the long duration of the follow-up, is that there were no participation or memory biases in it, which are typical of the previous studies, and for which the results of the studies done so far are not solid. Although this study is free of the known biases and therefore its findings are of greater weight, there will certainly be more skeptics and those who are "convinced" of a connection that probably does not exist.

Dr. Micha Barhana, School of Public Health, Faculty of Welfare and Health Sciences, University of Haifa

for further reading:

Banks E, Canfell K, Reeves G. HRT and breast cancer: recent findings in the context of the evidence to date. Womens Health (Lond Engl). 2008 Sep. 4(5): 427-31.

Gorenoi V, Schönermark MP, Hagen A. Benefits and risks of hormonal contraception for women. GMS Health Technol Assess. 2007 10; 3:Doc06.

Ness RB, Grisso JA, Klapper J, Schlesselman JJ, Silberzweig S, Vergona R, Morgan M, Wheeler JE. Risk of ovarian cancer in relation to estrogen and progestin dose and use characteristics of oral contraceptives. SHARE Study Group. Steroid Hormones and Reproductions. Am J Epidemiol. 2000 1;152 (3):233-41.

Hardell L, Carlberg M, Hansson Mild K. Mobile phone use and the risk for malignant brain tumors: a case-control study on deceased cases and controls. Neuroepidemiology. 2010 Aug; 35(2):109-14.

Inskip PD, Hoover RN, Devesa SS. Brain cancer incidence trends in relation to cellular telephone use in the United States. Neuro Oncol. 2010 Nov;12(11):1147-51.

Lehrer S, Green S, Stock RG. Association between number of cell phone contracts and brain tumor incidence in nineteen US States. J Neurooncol. 2011 Feb; 101(3):505-7.

Deltour I, Johansen C, Auvinen A, Feychting M, Klaeboe L, Schüz J. Time trends in brain tumor incidence rates in Denmark, Finland, Norway, and Sweden, 1974-2003. J Natl Cancer Inst. 2009 Dec 16; 101(24):1721-4.

The full article was published in Galileo magazine, February 2012