REFLEXIÓN FINAL Y PERSONAL

Epidemiological research

Since the introduction and rapid spread of mobile telephones in the 1990s, the question as to whether the radiofrequency electromagnetic fields of cellular phones increase brain tumour risk has become an in- creasingly important public health concern. The use of mobile phones is so widespread that even a small tumour risk due to exposure to radiofrequency radi- ation emitted by cellular phones would result in in- creases in general population incidence rates. The In- terphone study is the largest epidemiological study of mobile phone use and brain tumours to date. This case-control study included 13 countries, with coor- dination by the World Health Organization (WHO). Case-control is a retrospective epidemiological study design where people with a disease (cases) are matched with people who do not have the disease

(controls). The studies compare the groups with re- spect to past exposure to the potential risk factor and look for differences. For example, if it were found that persons with brain tumours used their mobile phones significantly more often than comparable control persons, that would be an indication of increased risk.

The overall evaluation of the Interphone study is based on 2,400 cases of meningioma (brain tumours that develop from the meninges), 2,700 cases of gli- oma (brain tumours arising from glial cells), and 5,600 matched controls with no brain cancer, in peo- ple 30–60 years of age [1]. Evaluation of all data re- vealed a 20 % lower risk of meningioma and glioma for regular mobile phone users compared to non

Prof. Martin Röösli, PhD

Head of the Unit for Environmental Epidemiology and Risk Assessment, Swiss Tropical and Public Health Institute, Basel

Kerstin Hug, MD

Responsible for the Documentation and Service Database ELMAR – Electromagnetic Radiation and Health, Swiss Tropical and Public Health Institute, Basel

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1. The influence of confounders

In observational study designs, cancer incidence is compared in dependency upon mobile phone use. Here there is always the question as to how compa- rable the participants with high mobile telephone use are with the participants with no or infrequent phone use. If there is a difference in cancer rates between cellular phone users and non-users, the reason is not necessarily mobile phone radiation. The two groups may differ in other characteristics or be- haviours that affect cancer risk. These confounders can distort the results of a study.

This problem became particularly evident in a large Danish cohort study [3]. In cohort studies it is exam- ined whether a group of persons who are exposed to a potential risk factor have a higher incidence of dis- ease than persons in a control group that is not ex- posed or less exposed to this factor. In the study in Denmark, as compared to the rest of the population long-term mobile phone users were found to have a lower risk of brain tumours. At the same time, among men, long-term cellular phone users were also found to have a lower risk of lung cancer. Among women, long-term mobile phone users had a higher risk of uterine cancer. As it is very unlikely that cellular phone radiation affects lung cancer risk or uterine cancer risk, this indicated that other lifestyle factors could have led to the results. A plausible explanation, for example, is that men who started using mobile phones shortly after they were first introduced may have had higher incomes and may have smoked less. 2. Distortion of results due to selection bias In principle, lifestyle factors that also affect cancer risk, such as smoking or alcohol consumption, could be captured and taken into consideration in the anal- ysis. In the Danish study, however, no such informa- tion was available because the study was based on regular users. However, in a subset of users – the

highest users, with a history of at least 1,640 hours of call time – the risk of glioma was 40 % higher com- pared to non regular users. These contradictory find- ings raise the question of the explanatory power of epidemiological studies.

The conclusiveness of environmental epidemio- logical studies

Demonstrating cancer risk due to exposure to envi- ronmental factors is particularly difficult because the negative effects may occur only after a long period of exposure. To determine how a potentially harmful substance affects the organism and what biological processes are involved, experimental studies with cells or animals are helpful. However, the extent to which the findings can be applied to human beings is always uncertain, so that in the end only longitudinal studies with people can provide definitive answers. The WHO also attaches the most importance to these epidemiological studies [2].

Studies with human participants present a number of practical difficulties. The type of study least prone to error would be a very large randomised trial in which half of the participants were randomly assigned to mobile phone exposure for 10 years and the other half were not. Naturally, studying cancer risk in that way is not feasible for ethical and practical reasons, so we must rely on the findings of observational ep- idemiological studies. The three biggest difficulties with these studies are presented in the following tak- ing the example of studies on mobile phone use.

195 data from cancer registries. In the Interphone study,

great efforts were undertaken to capture all possible confounders by personally surveying all study partic- ipants. Due to the effort required, willingness to par- ticipate in such a study can depend on the state of health of the participants as well as their mobile phone use, and it is generally not very high, espe- cially among healthy participants. Already at the start a low rate of participation in one of the groups can result in systematic differences between the groups to be compared and thus lead to a distortion of the study results.

There are indications that this is what happened in the Interphone study: Since willingness to take part in the study was particularly low in healthy control persons who did not use cellular phones, mobile phone users came to be overrepresented in the con- trol group. Through this, the cellular phone use of healthy persons compared to persons with brain tumours was overestimated, and the statistical anal- yses yielded a seemingly reduced risk of cancer with regular mobile phone use.

3. Estimating exposure

The third big difficulty with observational studies in epidemiology is estimating and classifying exposure correctly. Retrospective studies like the Interphone study must frequently rely on participants’ self-re- ports, as no objective exposure data for the past, for instance from network providers, are available. Since people do not recall the exact number and duration of phone calls years or decades ago, their self-re- ports are fraught with great uncertainties. If patients and healthy participants make on average the same errors in their exposure estimates and if there is a correlation between the exposure estimates and ac- tual call time, the effect on the results is not dra- matic. The resulting erroneous classification of the participants leads to an underestimate of the associ-

ation, if there is a connection between exposure and disease. And if there is no connection, the study will not erroneously compute an association.

However, it is problematic if self-reports differ be- tween patients and control persons. It is known that persons with a disease tend to overestimate their past exposure to environmental risk factors, because they are looking for reasons why they became ill. In contrast, persons without a disease tend to under- estimate their exposure. As a result of this constella- tion, study results can mistakenly indicate an associ- ation between exposure and disease that in reality does not exist. Whether or not this phenomenon is the reason for the increased risk of glioma among mobile phone users with the highest exposure levels in the Interphone study cannot be determined con- clusively and is a matter of controversy in expert cir- cles.

Brain tumours caused by mobile phones?

Epidemiological studies are needed to clarify the long-term risks of exposure to potential environmen- tal factors such as electromagnetic fields. However, due to their non-experimental design the studies are prone to errors. For this reason it is necessary to in- vestigate a question using different types of studies in different contexts. The complementary informa- tion provided by the different studies yields an over- all picture that allows us to assess the scientific evi- dence.

As mentioned, the Interphone study and other simi- lar, previously conducted studies did not conclusively determine whether mobile phone use increases brain tumour risk. If it did, the widespread and nearly global use of mobile communications would lead us to expect an increase in brain tumour incidence. However, higher incidence rates have not been found

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based on evaluations of cancer registry data in Scan- dinavia [4], England [5], or the United States [6]. Al- though these data tend to speak against an associa- tion, it should be noted that long-term risk that would become manifest after more than 20 years of expo- sure is not yet discernible in the current incidence rates. In summary, the evidence to date does not in- dicate that cellular phone use causes an increase in brain tumour risk. But there are still only few studies on mobile phone use longer than 15 years and on the effects of cellular phone use on children and adoles- cents.

References

1. Interphone Study Group. Brain tumour risk in relation to mobile telephone use: results of the Interphone international case-control study. Int J Epidemiol. 2010 Jun;39(3):675-94.

2. International Agency for Research on Cancer (IARC). IARC monographs on the evaluation of carcinogenic risks to humans. Non-Ionizing radiation, part 1: static and extremely low-frequency (ELF) electric and magnetic fields, volume 80. Geneva: World Health Organization and IARC Press; 2002.

3. Schüz J, Jacobsen R, Olsen JH, Boice JD Jr, McLaughlin JK, Johansen C. Cellular telephone use and cancer risk: update of a nationwide Danish cohort. J Natl Cancer Inst. 2006 Dec 6;98(23):1707-13.

4. 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.

5. de Vocht F, Burstyn I, Cherrie JW. Time trends (1998–2007) in brain cancer incidence rates in relation to mobile phone use in England. Bioelectromagnetics. 2011 Jul;32(5):334-9. doi: 10.1002/bem.20648. Epub 2011 Jan 28.

6. 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.

Prof. Martin Röösli, PhD

Martin Röösli is an environmental epidemiologist with a background in atmospheric science. He is head of the Unit for Environ- mental Epidemiology and Risk Assessment at the Swiss Tropical and Public Health Institute. His research deals with the effects of environmental factors on health, such as electromagnetic fields, air pollution, noise, ioniz- ing and non-ionizing radiation, and passive smoking. Phone +41 (0)61 284 33 88,

[email protected] www.swisstph.ch

Kerstin Hug, MD

Kerstin Hug is a research assistant at the Swiss Tropical and Public Health Institute and is responsible for the ELMAR Documentation Service and Database on electro- magnetic radiation and health. In her work she focuses on sys- tematic literature research, meth- odological evaluation of epidemi- ological studies, and writing reviews of the literature on non-ionizing radiation.

Phone +41 (0)61 284 83 66 [email protected] www.elmar.unibas.ch

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The importance of cancer registries for health policy

Cancer is a significant disease in Switzerland: Four out of ten people are diagnosed with cancer at some point in their lives, and 16,000 people die of cancer each year. The number of cases of cancer in Switzerland is expected to increase in the future due to the ageing population.

Switzerland must have reliable data to monitor the development of cancer, to better under- stand the causes of cancer, and to assess the effectiveness and quality of prevention and treatment. These data are systematically collected by cantonal cancer registries and then aggregated and analyzed on a national level by the National Institute for Cancer Epidemiol- ogy and Registration (NICER). In February 2011 NICER, the Swiss Childhood Cancer Regis- try (SCCR), and the Federal Statistical Office (FSO) published the report “Cancer in Swit- zerland: Situation and development from 1983 to 2007”. This report provides an overview of the national cancer incidence and many other aspects of cancer, and it is an important, evidence-based foundation for decision-making in politics, prevention, and medical prac- tice.

At present there are 16 cantonal or regional cancer registries, which cover only about two- thirds of the population of Switzerland. Therefore, for estimates for the whole of Switzer- land these figures have to be extrapolated. Since it is assumed that there are differences in cancer incidence among the different language regions of Switzerland, certain distortions of the data are possible. These statistical problems will be solved only once there is full- coverage data collection in all cantons. NICER and the cancer registries therefore support the continued efforts of the Federal Council to create a basis in federal law for full-cover- age, nationally coordinated cancer registration in Switzerland.

National Institute for Cancer Epidemiology and Registration (NICER)

c/o ISPMZ University of Zurich Seilergraben 49 CH-8001 Zurich Phone +41 (0)44 634 53 74 [email protected] www.nicer.org

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Epidemiological research

List of completed research projects from July 2008 to December 2010

Bouchardy Christine | KLS 01759-08-2005 | CHF 310 600.–

Registre genevois des tumeurs, Institut national pour l’épidémiologie et l’enregistrement du cancer (NICER), Genève

Epidemiologic research on the impact of genetic factors in breast cancer occurrence among the female population of Geneva: A study from the first Familial breast cancer registry in Switzerland

Ess Silvia | KLS 01766-08-2005 | CHF 259 500.–

Krebsregister St. Gallen-Appenzell, Kantonsspital St. Gallen, St. Gallen

Patterns of care and survival in breast cancer patients in Switzerland

Levi Fabio | OCS 01633-02-2005 | CHF 265 620.–

Unité d’épidémiologie du cancer et Registres vaudois et neuchâtelois des tumeurs, Institut universitaire de médecine sociale et préventive, Centre hospitalier universitaire vaudois (CHUV), Lausanne

An integrated network of case­control studies on cancer: Nutrition, other environmental and genetic factors

Zwahlen Marcel | OCS 01869-02-2006 | CHF 171 400.–

Institut für Sozial- und Präventivmedizin, Universität Bern, Bern

Risk of childhood leukemia varies little by familial socio­economic status – while survival time after a brain tumor diagnosis varied considerably by familial socio­economic status

Potential patient benefit

These studies will allow to a better understanding of the genetic factors influencing disease prognosis and make it possible in the near future to improve surveillance and care of women with high risk breast cancer.

Project coordinator

Prof. Dr Christine Bouchardy Registre genevois des tumeurs

Institut de médecine sociale et préventive

Département de médecine et santé communautaire Université de Genève

Bd de la Cluse 55 CH-1205 Genève

Phone +41 (0)22 379 49 50

[email protected]

Bouchardy Christine | Epidemiologic research on the impact of genetic factors in breast cancer occur- rence among the female population of Geneva: A study from the first Familial breast cancer registry in Switzerland (KFS 01759-08-2005)

Breast cancer is a public health priority in Switzerland. Family history is one of the major risk factors for breast cancer. To perform innovative studies on the effect of hereditary factors on breast cancer occurrence and outcome, we set up the first and unique Familial breast cancer registry in Switzerland, which currently contains validated family histories of cancer for more than 6,000 patients.

Objectives of the study

The objectives of our study are to compare pathological characteristics of cancers occurring in the same family and to evaluate the concordance of prognosis between first- degree relatives with breast cancer.

Methods

We will compare tumour characteristics between women with breast cancer belonging to the same family, and in- vestigate whether the mother or sister’s prognosis influ- ences the patient’s prognosis.

Epidemiological research