Abstract compilation from Dr. Preetha Rajaraman and Dr. Martha Linet from the National Cancer Institute, National Institutes of Health.

Transcription

1 Abstract compilation from Dr. Preetha Rajaraman and Dr. Martha Linet from the National Cancer Institute, National Institutes of Health. Epidemiologic Evidence on Mobile Phones and Tumor Risk: A Review Anders Ahlbom,a Maria Feychting,a Adele Green,b Leeka Kheifets,c David A. Savitz,d Anthony J. Swerdlow,e and ICNIRP (International Commission for Non Ionizing Radiation Protection) Standing Committee on Epidemiology Epidemiology Volume 20, Number 5, September 2009 Discussion/Action Item 1d CEAC April 7, 2011 Abstract: This review summarizes and interprets epidemiologic evidence bearing on a possible causal relation between radiofrequency field exposure from mobile phone use and tumor risk. In the last few years, epidemiologic evidence on mobile phone use and the risk of brain and other tumors of the head in adults has grown in volume, geographic diversity of study settings, and the amount of data on longerterm users. However, some key methodologic problems remain, particularly with regard to selective nonresponse and inaccuracy and bias in recall of phone use. Most studies of glioma show small increased or decreased risks among users, although a subset of studies show appreciably elevated risks. We considered methodologic features that might explain the deviant results, but found no clear explanation. Overall the studies published to date do not demonstrate an increased risk within approximately 10 years of use for any tumor of the brain or any other head tumor. Despite the methodologic shortcomings and the limited data on long latency and long term use, the available data do not suggest a causal association between mobile phone use and fast growing tumors such as malignant glioma in adults (at least for tumors with short induction periods). For slow growing tumors such as meningioma and acoustic neuroma, as well as for glioma among long term users, the absence of association reported thus far is less conclusive because the observation period has been too short. Epidemiology of Health Effects of Radiofrequency Exposure ICNIRP (International Commission for Non Ionizing Radiation Protection) Standing Committee on Epidemiology: Anders Ahlbom,1,2 Adele Green,3 Leeka Kheifets,4 David Savitz,5 and Anthony Swerdlow6 1Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 2Stockholm Center for Public Health, Stockholm, Sweden; 3Epidemiology and Public Health Unit, Queensland Institute of Medical Research, Brisbane, Australia; 4Department of Epidemiology, School of Public Health, University of California at Los Angeles, Los Angeles, California, USA; 5Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 6Section of Epidemiology, Institute of Cancer Research, Sutton, Surrey, United Kingdom Environmental Health Perspectives VOLUME 112 NUMBER 17 December 2004 Abstract: We have undertaken a comprehensive review of epidemiologic studies about the effects of radiofrequency fields (RFs) on human health in order to summarize the current state of knowledge, explain the methodologic issues that are involved, and aid in the planning of future studies. There have been a large number of occupational studies over several decades, particularly on cancer, cardiovascular disease, adverse reproductive outcome, and cataract, in relation to RF exposure.

2 More recently, there have been studies of residential exposure, mainly from radio and television transmitters, and especially focusing on leukemia. There have also been studies of mobile telephone users, particularly on brain tumors and less often on other cancers and on symptoms. Results of these studies to date give no consistent or convincing evidence of a causal relation between RF exposure and any adverse health effect. On the other hand, the studies have too many deficiencies to rule out an association. A key concern across all studies is the quality of assessment of RF exposure. Despite the ubiquity of new technologies using RFs, little is known about population exposure from RF sources and even less about the relative importance of different sources. Other cautions are that mobile phone studies to date have been able to address only relatively short lag periods, that almost no data are available on the consequences of childhood exposure, and that published data largely concentrate on a small number of outcomes, especially brain tumor and leukemia. Cellular Telephone Use and Risk of Acoustic Neuroma Helle Collatz Christensen1, Joachim Schüz2, Michael Kosteljanetz3, Hans Skovgaard Poulsen4, Jens Thomsen5, and Christoffer Johansen1 1 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. 2 Institute for Medical Biostatistics, Epidemiology and Informatics, University of Mainz, Mainz, Germany. 3 Neurosurgical Department, Neuroscience Centre, University Hospital of Copenhagen, Copenhagen, Denmark. 4 Department of Radiation Biology, Finsen Centre, University Hospital of Copenhagen, Copenhagen, Denmark. 5 Department of Otolaryngology Head and Neck Surgery, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. Am J Epidemiol 2004;159: Despite limited evidence, cellular telephones have been claimed to cause cancer, especially in the brain. In this Danish study, the authors examined the possible association between use of cellular telephones and development of acoustic neuroma. Between 2000 and 2002, they ascertained 106 incident cases and matched these persons with 212 randomly sampled, population based controls on age and sex. The data obtained included information on use of cellular telephones from personal interviews, data from medical records, and the results of radiologic examinations. The authors obtained information on socioeconomic factors from Statistics Denmark. The overall estimated relative risk of acoustic neuroma was 0.90 (95% confidence interval: 0.51, 1.57). Use of a cell phone for 10 years or more did not increase acoustic neuroma risk over that of short term users. Furthermore, tumors did not occur more frequently on the side of the head on which the telephone was typically used, and the size of the tumor did not correlate with the pattern of cell phone use. The results of this prospective, population based, nationwide study, which included a large number of long term users of cellular telephones, do not support an association between cell phone use and risk of acoustic neuroma.

3 Cellular telephones and risk for brain tumors: A population based, incident case control study H. Collatz Christensen, MD; J. Schüz, PhD; M. Kosteljanetz, DMSc, MD; H. Skovgaard Poulsen, DMSc, MD; J.D. Boice, Jr., ScD; J.K. McLaughlin, PhD; and C. Johansen, PhD, DMSc, MD NEUROLOGY 2005;64: Abstract Objective: To evaluate a possible association of glioma or meningioma with use of cellular telephones, using a nationwide population based case control study of incident cases of meningioma and glioma. Methods: The authors ascertained all incident cases of glioma and meningioma diagnosed in Denmark between September 1, 2000, and August 31, They enrolled 252 persons with glioma and 175 persons with meningioma aged 20 to 69. The authors also enrolled 822 randomly sampled, population based controls matched for age and sex. Information was obtained from personal interviews, medical records containing diagnoses, and the results of radiologic examinations. For a small number of cases and controls, the authors obtained the numbers of incoming and outgoing calls. They evaluated the memory of the respondents with the Mini Mental State Examination and obtained data on socioeconomic factors from Statistics Denmark. Results: There were no material socioeconomic differences between cases and controls or participants and nonparticipants. Use of cellular telephone was associated with a low risk for high grade glioma (OR, 0.58; 95% CI, 0.37 to 0.90). The risk estimates were closer to unity for low grade glioma (1.08; 0.58 to 2.00) and meningioma (1.00; 0.54 to 1.28). Conclusion: The results do not support an association between use of cellular telephones and risk for glioma or meningioma. Mobile phones, cordless phones and the risk for brain tumours LENNART HARDELL and MICHAEL CARLBERG Department of Oncology, Orebro University Hospital, SE Orebro, Sweden INTERNATIONAL JOURNAL OF ONCOLOGY 35: 5 17, 2009 Abstract. The Hardell group conducted during two case control studies on brain tumours including assessment of use of mobile phones and cordless phones. The questionnaire was answered by 905 (90%) cases with malignant brain tumours, 1,254 (88%) cases with benign tumours and 2,162 (89%) population based controls. Cases were reported from the Swedish Cancer Registries. Anatomical area in the brain for the tumour was assessed and related to side of the head used for both types of wireless phones. In the current analysis we defined ipsilateral use (same side as the tumour) as 50% of the use and contralateral use (opposite side) as <50% of the calling time. We report now further results for use of mobile and cordless phones. Regarding astrocytoma we found highest risk for ipsilateral mobile phone use in the >10 year latency group, OR=3.3, 95% CI= and for cordless phone use OR=5.0, 95% CI= In total, the risk was highest for cases with first use <20 years age, for mobile phone OR=5.2, 95% CI= and for cordless phone OR=4.4, 95% CI= For acoustic neuroma, the highest OR was found for ipsilateral use and >10 year latency, for mobile phone OR=3.0, 95% CI= and cordless phone OR=2.3, 95% CI= Overall highest OR for mobile phone use was found in subjects with first

4 use at age <20 years, OR=5.0, 95% CI whereas no association was found for cordless phone in that group, but based on only one exposed case. The annual age adjusted incidence of astrocytoma for the age group >19 years increased significantly by +2.16%, 95% CI to during in Sweden in spite of seemingly underreporting of cases to the Swedish Cancer Registry. A decreasing incidence was found for acoustic neuroma during the same period. However, the medical diagnosis and treatment of this tumour type has changed during recent years and underreporting from a single center would have a large impact for such a rare tumour. Mobile phone use and risk of glioma in adults: case control study Sarah J Hepworth, Minouk J Schoemaker, Kenneth R Muir, Anthony J Swerdlow, Martie J A van Tongeren, Patricia A McKinney BMJ, doi: /bmj (published 20 January 2006) Abstract Objective To investigate the risk of glioma in adults in relation to mobile phone use. Design Population based case control study with collection of personal interview data. Setting Five areas of the United Kingdom. Participants 966 people aged 18 to 69 years diagnosed with a glioma from 1 December 2000 to 29 February 2004 and 1716 controls randomly selected from general practitioner lists. Main outcome measures Odds ratios for risk of glioma in relation to mobile phone use. Results The overall odds ratio for regular phone use was 0.94 (95% confidence interval 0.78 to 1.13). There was no relation for risk of glioma and time since first use, lifetime years of use, and cumulative number of calls and hours of use. A significant excess risk for reported phone use ipsilateral to the tumour (1.24, 1.02 to 1.52) was paralleled by a significant reduction in risk (0.75, 0.61 to 0.93) for contralateral use. Conclusions Use of a mobile phone, either in the short or medium term, is not associated with an increased risk of glioma. This is consistent with most but not all published studies. The complementary positive and negative risks associated with ipsilateral and contralateral use of the phone in relation to the side of the tumour might be due to recall bias. Colorectal cancers in Martinique: incidence and mortality rates over a period of 20 years P. Ngasseua,b,*, M. Dieyea,b, J. Veronique Baudina,b, C. Draganescua, M. J. Dorivalb, M. Ossondoc, J. Smith Ravind, H. Azalouxa,b a Service de médecine nucléaire oncologie, CHU de Fort de France, GREFCC, université des Antilles Guyane, Martinique b Registre des cancers de la Martinique, AMREC, le Lamentin, Martinique c Service d anatomopathologie, CHU de Fort de France, Martinique d UFR des sciences exactes, campus de Fouillole, Pointe à Pitre, GREFCC, université des Antilles Guyane, Guadeloupe Revue d Épidémiologie et de Santé Publique 55 (2007) Abstract

5 Background. Colorectal cancer is the second leading cause of cancer death in Western countries, with an incidence progressively increasing in developing countries. Worldwide, colorectal cancer is the second and third leading cause of death by cancer in females and males respectively. According to the Martinique Cancer Register data, colorectal cancer is the second leading cause of death by cancer in women, and the fourth in men. Colorectal cancer exhibits a variable distribution worldwide. This study was conducted to observe variations in colorectal incidence and mortality rates observed over a twentyyear period. Such data will be useful for monitoring changing trends related to onset of an organized screening program. Method. Patients with colorectal cancer diagnosed from 1981 to 2000 in Martinique were included in this study. Data are obtained from the Martinique Cancer Register. Results. The incidence of colorectal cancer in Martinique (16/100,000 and 17/100,000 in the female and male population respectively in the year 2000) is intermediary compared with other countries worldwide. There is a current trend towards increased incidence and mortality. The incidence has increased for cancers localized in the proximal colon, the sigmoid colon and the rectum. Conclusion. The increasing incidence of colorectal cancer in all localisations raises concern in Martinique. A significant predominance of colorectal cancer incidence among the male population in Martinique was not observed. Gender and age do not appear to imply any preferential localisation of colorectal cancer. CELLULAR TELEPHONE USE AND BRAIN TUMORS PETER D. INSKIP, SC.D., ROBERT E. TARONE, PH.D., ELIZABETH E. HATCH, PH.D., TIMOTHYC. WILCOSKY, PH.D.,WILLIAMR. SHAPIRO, M.D., ROBERTG. SELKER, M.D., HOWARDA. FINE, M.D., PETERM. BLACK, M.D.,JAYS. LOEFFLER, M.D.,AND MARTHAS.LINET, M.D. N Engl J Med, Vol. 344, No. 2 ABSTRACT Background Concern has arisen that the use of hand held cellular telephones might cause brain tumors. If such a risk does exist, the matter would be of considerable public health importance, given the rapid increase worldwide in the use of these devices. Methods We examined the use of cellular telephones in a case control study of intracranial tumors of the nervous system conducted between 1994 and We enrolled 782 patients through hospitals in Phoenix, Arizona; Boston; and Pittsburgh; 489 had histologically confirmed glioma, 197 had meningioma, and 96 had acoustic neuroma. The 799 controls were patients admitted to the same hospitals as the patients with brain tumors for a variety of nonmalignant conditions. Results As compared with never, or very rarely, having used a cellular telephone, the relative risks associated with a cumulative use of a cellular telephone for more than 100 hours were 0.9 for glioma (95 percent confidence interval, 0.5 to 1.6), 0.7 for meningioma (95 percent confidence interval, 0.3 to 1.7), 1.4 for acoustic neuroma (95 percent confidence interval, 0.6 to 3.5), and 1.0 for all types of tumors combined (95 percent confidence interval, 0.6 to 1.5). There was no evidence that the risks were higher among persons who used cellular telephones for 60 or more minutes per day or regularly for five or more years. Tumors did not occur disproportionately often on the side of head on which the telephone was typically used. Conclusions

6 These data do not support the hypothesis that the recent use of hand held cellular telephones causes brain tumors, but they are not sufficient to evaluate the risks among long term, heavy users and for potentially long induction periods. (N Engl J Med 2001;344:79 86.) Brain cancer incidence trends in relation to cellular telephone use in the United States Peter D. Inskip, Robert N. Hoover, and Susan S. Devesa Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (P.D.I., R.N.H., S.S.D.) Neuro Oncology doi: /neuonc/noq077 The use of cellular telephones has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States. If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable. One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long term users. To address this issue, we examined temporal trends in brain cancer incidence rates in the United States, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. Log linear models were used to estimate the annual percent change in rates among whites. With the exception of the year age group, the trends for were downward or flat. Among those aged years, there was a statistically significant increasing trend between 1992 and 2006 among females but not among males. The recent trend in year old women was driven by a rising incidence of frontal lobe cancers. No increases were apparent for temporal or parietal lobe cancers, or cancers of the cerebellum, which involve the parts of the brain that would be more highly exposed to radiofrequency radiation from cellular phones. Frontal lobe cancer rates also rose among year old males, but the increase began earlier than among females and before cell phone use was highly prevalent. Overall, these incidence data do not provide support to the view that cellular phone use causes brain cancer. Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case control study: The INTERPHONE Study Group* *Author list lengthy, included in appendix Corresponding author. Elisabeth Cardis; CREAL, Doctor Aiguader 88, Barcelona, Spain. E mail: ecardis@creal.cat International Journal of Epidemiology 2010;39: doi: /ije/dyq079 Background The rapid increase in mobile telephone use has generated concern about possible health risks related to radiofrequency electromagnetic fields from this technology. Methods An interview based case control study with 2708 glioma and 2409 meningioma cases and matched controls was conducted in 13 countries using a common protocol. Results A reduced odds ratio (OR) related to ever having been a regular mobile phone user was seen for glioma [OR 0.81; 95% confidence interval (CI) ] and meningioma (OR 0.79; 95% CI ), possibly reflecting participation bias or other methodological limitations. No elevated OR was observed 510 years after first phone use (glioma: OR 0.98; 95% CI ; meningioma: OR 0.83; 95% CI 0.61

7 1.14). ORs were <1.0 for all deciles of lifetime number of phone calls and nine deciles of cumulative call time. In the 10th decile of recalled cumulative call time, h, the OR was 1.40 (95% CI ) for glioma, and 1.15 (95% CI ) for meningioma; but there are implausible values of reported use in this group. ORs for glioma tended to be greater in the temporal lobe than in other lobes of the brain, but the CIs around the lobe specific estimates were wide. ORs for glioma tended to be greater in subjects who reported usual phone use on the same side of the head as their tumour than on the opposite side. Conclusions Overall, no increase in risk of glioma or meningioma was observed with use of mobile phones. There were suggestions of an increased risk of glioma at the highest exposure levels, but biases and error prevent a causal interpretation. The possible effects of long term heavy use of mobile phones require further investigation. The INTERPHONE study: design, epidemiological methods, and description of the study population Elisabeth Cardis, Lesley Richardson, Isabelle Deltour, Bruce Armstrong, Maria Feychting, Christoffer Johansen, Monique Kilkenny, Patricia McKinney, Baruch Modan, Siegal Sadetzki, Joachim Schu z, Anthony Swerdlow, Martine Vrijheid, Anssi Auvinen, Gabriele Berg, Maria Blettner, Joseph Bowman, Julianne Brown, Angela Chetrit, Helle Collatz Christensen, Angus Cook, Sarah Hepworth, Graham Giles, Martine Hours, Ivano Iavarone, Avital Jarus Hakak, Lars Klaeboe, Daniel Krewski, Susanna Lagorio, Stefan Lo nn, Simon Mann, Mary McBride, Kenneth Muir, Louise Nadon, Marie Elise Parent, Neil Pearce, Tiina Salminen, Minouk Schoemaker, Brigitte Schlehofer, Jack Siemiatycki, Masao Taki, Toru Takebayashi, Tore Tynes, Martie van Tongeren, Paolo Vecchia, Joe Wiart, Alistair Woodward, Naohito Yamaguchi Eur J Epidemiol (2007) 22: DOI /s z Abstract. The very rapid worldwide increase in mobilephone use in the last decade has generated considerable interest in the possible health effects of exposure to radio frequency (RF) fields. A multinational case control study, INTERPHONE, was set up to investigate whether mobile phone use increases the risk of cancer and, more specifically, whether the RF fields emitted by mobile phones are carcinogenic. The study focused on tumours arising in the tissues most exposed to RF fields from mobile phones: glioma, meningioma, acoustic neurinoma and parotid gland tumours. In addition to a detailed history of mobile phone use, information was collected on a number of known and potential risk factors for these tumours. The study was conducted in 13 countries. Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the UK using a common core protocol. This paper describes the study design and methods and the main characteristics of the study population. INTERPHONE is the largest case control study to date investigating risks related to mobile phone use and to other potential risk factors for the tumours of interest and includes 2,765 glioma, 2,425 meningioma, 1,121 acoustic neurinoma, 109 malignant parotid gland tumour cases and 7,658 controls. Particular attention was paid to estimating the amount and direction of potential recall and participation biases and their impact on the study results.

8 Cellular Telephones and Cancer a Nationwide Cohort Study in Denmark Christoffer Johansen, John D. Boice, Jr., Joseph K. McLaughlin, Jørgen H. Olsen Journal of the National Cancer Institute, Vol. 93, No. 3, February 7, 2001 Background: Use of cellular telephones is increasing exponentially and has become part of everyday life. Concerns about possible carcinogenic effects of radiofrequency signals have been raised, although they are based on limited scientific evidence. Methods: A retrospective cohort study of cancer incidence was conducted in Denmark of all users of cellular telephones during the period from 1982 through Subscriber lists from the two Danish operating companies identified cellular telephone users. Cancer incidence was determined by linkage with the Danish Cancer Registry. All statistical tests are two sided. Results: Overall, 3391 cancers were observed with 3825 expected, yielding a significantly decreased standardized incidence ratio (SIR) of 0.89 (95% confidence interval [CI] = 0.86 to 0.92). A substantial proportion of this decreased risk was attributed to deficits of lung cancer and other smoking related cancers. No excesses were observed for cancers of the brain or nervous system (SIR = 0.95; 95% CI = 0.81 to 1.12) or of the salivary gland (SIR = 0.72; 95% CI = 0.29 to 1.49) or for leukemia (SIR = 0.97; 95% CI = ), cancers of a priori interest. Risk for these cancers also did not vary by duration of cellular telephone use, time since first subscription, age at first subscription, or type of cellular telephone (analogue or digital). Analysis of brain and nervous system tumors showed no statistically significant SIRs for a y subtype or anatomic location. Conclusions: The results of this investigation, the first nationwide cancer incidence study of cellular phone users, do not support the hypothesis of an association between use of these telephones and tumors of the brain or salivary gland, leukemia, or other cancers. Use of mobile phones in Norway and risk of intracranial tumours Lars Klaeboea, Karl Gerhard Blaasaasb and Tore Tynesa,c European Journal of Cancer Prevention 16: To test the hypothesis that exposure to radio frequency electromagnetic fields from mobile phones increases the incidence of gliomas, meningiomas and acoustic neuromas in adults. The incident cases were of patients aged years who were diagnosed during in Southern Norway. Population controls were selected and frequency matched for age, sex, and residential area. Detailed information about mobile phone use was collected from 289 glioma (response rate 77%), 207 meningioma patients (71%), and 45 acoustic neuroma patients (68%) and from 358 (69%) controls. For regular mobile phone use, defined as use on average at least once a week or more for at least 6 months, the odds ratio was 0.6 (95% confidence interval ) for gliomas, 0.8 (95% confidence interval ) for meningiomas and 0.5 (95% confidence interval ) for acoustic neuromas. Similar results were found with mobile phone use for 6 years or more for gliomas and acoustic neuromas. An exception was meningiomas, where the odds ratio was 1.2 (95% confidence interval ). Furthermore, no increasing trend was observed for gliomas or acoustic neuromas by increasing duration of regular use, the time since first regular use or cumulative use of mobile phones. The results from the present study indicate that use of mobile phones is not associated with an increased risk of gliomas, meningiomas or acoustic neuromas.

9 Selection Bias Due to Differential Participation in a Case Control Study of Mobile Phone Use and Brain Tumors ANNA LAHKOLA, MSC, TIINA SALMINEN, PHD, AND ANSSI AUVINEN, MD, PHD Ann Epidemiol 2005;15: PURPOSE: To evaluate the possible selection bias related to the differential participation of mobile phone users and non users in a Finnish case control study on mobile phone use and brain tumors. METHODS: Mobile phone use was investigated among 777 controls and 726 cases participating in the full personal interview (full participants), and 321 controls and 103 cases giving only a brief phone interview (incomplete participants). To assess selection bias, the Mantel Haenszel estimate of odds ratio was calculated for three different groups: full study participants, incomplete participants, and a combined group consisting of both full and incomplete participants. RESULTS: Among controls, 83% of the full participants and 73% of the incomplete participants had regularly used a mobile phone. Among cases, the figures were 76% and 64%, respectively. The odds ratio for brain tumor based on the combined group of full and incomplete participants was slightly closer to unity than that based only on the full participants. CONCLUSIONS: Selection bias tends to distort the effect estimates below unity, while analyses based on more comprehensive material gave results close to unity. Mobile phone use and risk of glioma in 5 North European countries Anna Lahkola1*, Anssi Auvinen1,2, Jani Raitanen1,2, Minouk J. Schoemaker3, Helle C. Christensen4, Maria Feychting5, Christoffer Johansen4, Lars Kl,boe6, Stefan L onn5, Anthony J. Swerdlow3, Tore Tynes6,7 and Tiina Salminen1,2 1STUK, Radiation and Nuclear Safety Authority, Helsinki, Finland 2Tampere School of Public Health, University of Tampere, Tampere, Finland 3Section of Epidemiology, Institute of Cancer Research, Sutton 4Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark 5Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden 6Institute of Population Based Cancer Research, The Cancer Registry of Norway, Oslo, Norway 7Norwegian Radiation Protection Authority, Østera s, Norway Int. J. Cancer: 120, (2007) Abstract. Public concern has been expressed about the possible adverse health effects of mobile telephones, mainly related to intracranial tumors. We conducted a population based case control study to investigate the relationship between mobile phone use and risk of glioma among 1,521 glioma patients and 3,301 controls. We found no evidence of increased risk of glioma related to regular mobile phone use (odds ratio, OR , 95%confidence interval, CI: 0.68, 0.91). No significant association was found across categories with duration of use, years since first use, cumulative number of calls or cumulative hours of use. When the linear trend was examined, the OR for cumulative hours of mobile phone use was (1.002, 1.010) per 100 hr, but no such relationship was found for the years of use or the number of calls.we found no increased risks when analogue and digital phones were analyzed separately. For more than 10 years of mobile phone use reported on the side of the head where the tumor was located, an increased OR of borderline statistical significance (OR , 95% CI 1.01, 1.92, p

10 trend 0.04) was found, whereas similar use on the opposite side of the head resulted in an OR of 0.98 (95%CI 0.71, 1.37). Although our results overall do not indicate an increased risk of glioma in relation to mobile phone use, the possible risk in the most heavily exposed part of the brain with long term use needs to be explored further before firm conclusions can be drawn. Meningioma and mobile phone use a collaborative case control study in five North European countries A Lahkola,1* T Salminen,1,2 J Raitanen,1,2 S Heina vaara,1 MJ Schoemaker,3 H Collatz Christensen,4 M Feychting,5 C Johansen,4 L Kl,boe,6,7 S Lo nn,5 AJ Swerdlow,3 T Tynes6,7 and A Auvinen1,2 International Journal of Epidemiology 2008;37: Background Use of mobile telephones has been suggested as a possible risk factor for intracranial tumours. To evaluate the effect of mobile phones on risk of meningioma, we carried out an international, collaborative case control study of 1209 meningioma cases and 3299 population based controls. Methods Population based cases were identified, mostly from hospitals, and controls from national population registers and general practitioners patient lists. Detailed history of mobile phone use was obtained by personal interview. Regular mobile phone use (at least once a week for at least 6 months), duration of use, cumulative number and hours of use, and several other indicators of mobile phone use were assessed in relation to meningioma risk using conditional logistic regression with strata defined by age, sex, country and region. Results Risk of meningioma among regular users of mobile phones was apparently lower than among never or non regular users (odds ratio, OR¼0.76, 95% confidence interval, CI 0.65, 0.89). The risk was not increased in relation to years since first use, lifetime years of use, cumulative hours of use or cumulative number of calls. The findings were similar regardless of telephone network type (analogue/digital), age or sex. Conclusions Our results do not provide support for an association between mobile phone use and risk of meningioma. Cellular telephones and non Hodgkin lymphoma Martha S. Linet1*, Theresa Taggart2, Richard K. Severson3, James R. Cerhan4,5, Wendy Cozen6, Patricia Hartge1 and Joanne Colt1 1Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MA 2Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 3Epidemiology Section, Karmanos Cancer Institute, Wayne State University, Detroit, MI 4Department of Preventive Medicine and Environmental Health, College of Medicine, University of Iowa, Iowa City, IA 5Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN 6Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA Int. J. Cancer: 119, (2006)

11 Dramatic increase in hand held cellular telephone use since the 1980s and excess risk of lymphoproliferative malignancies associated with radio frequency radiation (RFR) exposures in epidemiological and experimental studies motivated assessment of cellular telephones within a comprehensive US case control investigation of non Hodgkin lymphoma (NHL). A questionnaire ascertained cellular telephone use in 551 NHL cases and 462 frequency matched population controls. Compared to persons who had never used cellular telephones, risks were not increased among individuals whose lifetime use was fewer than 10 (odds ratio (OR) 5 0.9, 95% confidence intervals (CI): 0.6, 1.3), (OR 5 1.0, 95 % CI: 0.7, 1.5) or more than 100 times (e.g., regular users, OR 5 0.9, 95% CI: 0.6, 1.4). Among regular users compared to those who had never used hand held cellular telephones, risks of NHL were not significantly associated with minutes per week, duration, cumulative lifetime or year of first use, although NHL was non significantly higher in men who used cellular telephones for more than 8 years. Little evidence linked use of cellular telephones with total, diffuse large B cell lymphoma or follicular NHL. These findings must be interpreted in the context of less than 5% of the population reporting duration of use of 6 or more years or lifetime cumulative use of 200 or more hours. Mobile Phone Use and the Risk of Acoustic Neuroma Stefan Lo nn,* Anders Ahlbom,* Per Hall, and Maria Feychting* Epidemiology 2004;15: Background: Radiofrequency exposure from mobile phones is concentrated to the tissue closest to the handset, which includes the auditory nerve. If this type of exposure increases tumor risk, acoustic neuroma would be a potential concern. Methods: In this population based case control study we identified all cases age 20 to 69 years diagnosed with acoustic neuroma during 1999 to 2002 in certain parts of Sweden. Controls were randomly selected from the study base, stratified on age, sex, and residential area. Detailed information about mobile phone use and other environmental exposures was collected from 148 (93%) cases and 604 (72%) controls. Results: The overall odds ratio for acoustic neuroma associated with regular mobile phone use was 1.0 (95% confidence interval _ ). Ten years after the start of mobile phone use the estimates relative risk increased to 1.9 ( ); when restricting to tumors on the same side of the head as the phone was normally used, the relative risk was 3.9 ( ). Conclusions: Our findings do not indicate an increased risk of acoustic neuroma related to short term mobile phone use after a short latency period. However, our data suggest an increased risk of acoustic neuroma associated with mobile phone use of at least 10 years duration. Long Term Mobile Phone Use and Brain Tumor Risk Stefan Lo nn1, Anders Ahlbom1, Per Hall2, Maria Feychting1, and the Swedish Interphone Study Group 1 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 2 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. American Journal of Epidemiology

12 Handheld mobile phones were introduced in Sweden during the late 1980s. The purpose of this population based, case control study was to test the hypothesis that long term mobile phone use increases the risk of brain tumors. The authors identified all cases aged years who were diagnosed with glioma or meningioma during in certain parts of Sweden. Randomly selected controls were stratified on age, gender, and residential area. Detailed information about mobile phone use was collected from 371 (74%) glioma and 273 (85%) meningioma cases and 674 (71%) controls. For regular mobile phone use, the odds ratio was 0.8 (95% confidence interval: 0.6, 1.0) for glioma and 0.7 (95% confidence interval: 0.5, 0.9) for meningioma. Similar results were found for more than 10 years duration of mobile phone use. No risk increase was found for ipsilateral phone use for tumors located in the temporal and parietal lobes. Furthermore, the odds ratio did not increase, regardless of tumor histology, type of phone, and amount of use. This study includes a large number of long term mobile phone users, and the authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of glioma or meningioma. Mobile Phone Use and Risk of Parotid Gland Tumor Stefan Lo nn1, Anders Ahlbom1, Helle C. Christensen2, Christoffer Johansen2, Joachim Schu z2, Staffan Edstro m3, Gert Henriksson4, Jan Lundgren4, Johan Wennerberg5, and Maria Feychting1 1 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. 2 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. 3 Department of Otorhinolaryngology, Sahlgrenska University Hospital, Go teborg, Sweden. 4 Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden. 5 Department of Otorhinolaryngology, Head and Neck Surgery, Lund University Hospital, Lund, Sweden. American Journal of Epidemiology Handheld mobile phones were introduced in Denmark and Sweden during the late 1980s. This makes the Danish and Swedish populations suitable for a study aimed at testing the hypothesis that long term mobile phone use increases the risk of parotid gland tumors. In this population based case control study, the authors identified all cases aged years diagnosed with parotid gland tumor during in Denmark and certain parts of Sweden. Controls were randomly selected from the study population base. Detailed information about mobile phone use was collected from 60 cases of malignant parotid gland tumors (85% response rate), 112 benign pleomorphic adenomas (88% response rate), and 681 controls (70% response rate). For regular mobile phone use, regardless of duration, the risk estimates for malignant and benign tumors were 0.7 (95% confidence interval: 0.4, 1.3) and 0.9 (95% confidence interval: 0.5, 1.5), respectively. Similar results were found for more than 10 years duration of mobile phone use. The risk estimate did not increase, regardless of type of phone and amount of use. The authors conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of parotid gland tumors.

13 Cellular Phone Use and Risk of Benign and Malignant Parotid Gland Tumors A Nationwide Case Control Study Siegal Sadetzki1,2, Angela Chetrit1, Avital Jarus Hakak1, Elisabeth Cardis3, Yonit Deutch1, Shay Duvdevani4, Ahuva Zultan1, Ilya Novikov5, Laurence Freedman5, and Michael Wolf2,4 1 Cancer and Radiation Epidemiology Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel. 2 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. 3 Radiation Group, International Agency for Research on Cancer, Lyon, France. 4 Department of Otolaryngology Head and Neck Surgery, Chaim Sheba Medical Center, Tel Hashomer, Israel. 5 Biostatistics Unit, Gertner Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel. American Journal of Epidemiology The objective of this nationwide study was to assess the association between cellular phone use and development of parotid gland tumors (PGTs). The methods were based on the international INTERPHONE study that aimed to evaluate possible adverse effects of cellular phone use. The study included 402 benign and 58 malignant incident cases of PGTs diagnosed in Israel at age 18 years or more, in , and 1,266 population individually matched controls. For the entire group, no increased risk of PGTs was observed for ever having been a regular cellular phone user (odds ratio ¼ 0.87; p ¼ 0.3) or for any other measure of exposure investigated. However, analysis restricted to regular users or to conditions that may yield higher levels of exposure (e.g., heavy use in rural areas) showed consistently elevated risks. For ipsilateral use, the odds ratios in the highest category of cumulative number of calls and call time without use of hands free devices were 1.58 (95% confidence interval: 1.11, 2.24) and 1.49 (95% confidence interval: 1.05, 2.13), respectively. The risk for contralateral use was not significantly different from 1. A positive dose response trend was found for these measurements. Based on the largest number of benign PGT patients reported to date, our results suggest an association between cellular phone use and PGTs. Mobile phone use and risk of acoustic neuroma: results of the Interphone case control study in five North European countries MJ Schoemaker*,1, AJ Swerdlow1, A Ahlbom2,13, A Auvinen3,10, KG Blaasaas4, E Cardis5, H Collatz Christensen6, M Feychting2, SJ Hepworth7, C Johansen6, L Kl,boe8, S Lo nn2, PA McKinney7, K Muir9, J Raitanen10, T Salminen3, J Thomsen11 and T Tynes8,12 1Section of Epidemiology, Institute of Cancer Research, Brookes Lawley Building, Sutton SM2 5NG, UK; 2Institute of Environmental Medicine, Karolinska Institute, Box 210, , Stockholm, Sweden; 3STUK Radiation and Nuclear Safety Authority, Helsinki, Finland; 4Norwegian Armed Forces, Bygning 0028A, Sessvollmoen 2058, Norway; 5International Agency for Research on Cancer, 150 Cours Albert Thomas, Cedex 08, Lyon, France; 6Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark; 7Centre for Epidemiology and Biostatistics, University of Leeds, 30 Hyde Terrace, Leeds LS2 9LN, UK; 8The Cancer Registry of Norway, Institute of Population based Cancer Research, Montebello, 0310 Oslo, Norway; 9Division of Epidemiology and Public Health, University of Nottingham, Nottingham NG7 2UH, UK; 10Tampere School

14 of Public Health, University of Tampere, Tampere 33014, Finland; 11Department of Otolaryngology Head and Neck Surgery, Gentofte Hospital, University of Copenhagen, DK 2900 Hellerup, Denmark; 12Norwegian Radiation Protection Authority, PO Box 55, 1332 Osteras, Norway British Journal of Cancer (2005) 93, doi: /sj.bjc There is public concern that use of mobile phones could increase the risk of brain tumours. If such an effect exists, acoustic neuroma would be of particular concern because of the proximity of the acoustic nerve to the handset. We conducted, to a shared protocol, six population based case control studies in four Nordic countries and the UK to assess the risk of acoustic neuroma in relation to mobile phone use. Data were collected by personal interview from 678 cases of acoustic neuroma and 3553 controls. The risk of acoustic neuroma in relation to regular mobile phone use in the pooled data set was not raised (odds ratio (OR)¼0.9, 95% confidence interval (CI): ). There was no association of risk with duration of use, lifetime cumulative hours of use or number of calls, for phone use overall or for analogue or digital phones separately. Risk of a tumour on the same side of the head as reported phone use was raised for use for 10 years or longer (OR¼1.8, 95% CI: ). The study suggests that there is no substantial risk of acoustic neuroma in the first decade after starting mobile phone use. However, an increase in risk after longer term use or after a longer lag period could not be ruled out. Cellular Telephone Use and Cancer Risk: Update of a Nationwide Danish Cohort Joachim Schüz, Rune Jacobsen, Jørgen H. Olsen, John D. Boice Jr, Joseph K. McLaughlin, Christoffer Johansen J Natl Cancer Inst 2006;98: Background: The widespread use of cellular telephones has heightened concerns about possible adverse health effects. The objective of this study was to investigate cancer risk among Danish cellular telephone users who were followed for up to 21 years. Methods: This study is an extended follow up of a large nationwide cohort of persons whose fi rst cellular telephone subscription was between 1982 and 1995 and who were followed through 2002 for cancer incidence. Standardized incidence ratios (SIRs) were calculated by dividing the number of observed cancer cases in the cohort by the number expected in the Danish population. Results: A total of cancers were observed (SIR = 0.95; 95% confi dence interval [CI] = 0.93 to 0.97) for men and women combined. Cellular telephone use was not associated with increased risk for brain tumors (SIR = 0.97), acoustic neuromas (SIR = 0.73), salivary gland tumors (SIR = 0.77), eye tumors (SIR = 0.96), or leukemias (SIR = 1.00). Among long term subscribers of 10 years or more, cellular telephone use was not associated with increased risk for brain tumors (SIR = 0.66, 95% CI = 0.44 to 0.95), and there was no trend with time since fi rst subscription. The risk for smoking related cancers was decreased among men (SIR = 0.88, 95% CI = 0.86 to 0.91) but increased among women (SIR = 1.11, 95% CI = 1.02 to 1.21). Additional data on income and smoking prevalence, primarily among men, indicated that cellular telephone users who started subscriptions in the mid 1980s appeared to have a higher income and to smoke less than the general population.

15 Conclusions: We found no evidence for an association between tumor risk and cellular telephone use among either short term or longterm users. Moreover, the narrow confi dence intervals provide evidence that any large association of risk of cancer and cellular telephone use can be excluded. The Possible Role of Radiofrequency Radiation in the Development of Uveal Melanoma Andreas Stang,1 Gerasimos Anastassiou,2 Wolfgang Ahrens,1,3 Katja Bromen,1 Norbert Bornfeld,2 and Karl Heinz Jöckel1 Epidemiology 2001;12:7 12 There are few epidemiologic studies dealing with electromagnetic radiation and uveal melanoma. The majority of these studies are exploratory and are based on job and industry titles only. We conducted a hospital based and population based case control study of uveal melanoma and occupational exposures to different sources of electromagnetic radiation, including radiofrequency radiation. We then pooled these results. We interviewed a total of 118 female and male cases with uveal melanoma and 475 controls matching on sex, age, and study regions. Exposure to radiofrequency transmitting devices was rated as (a) no radiofrequency radiation exposure, (b) possible exposure to mobile phones, or (c) probable/certain exposure to mobile phones. Exposures were rated independently by two of the authors who did not know case or control status. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). We found an elevated risk for exposure to radiofrequency transmitting devices (exposure to radio sets, OR 5 3.0, 95% CI ; probable/certain exposure to mobile phones, OR 5 4.2, 95% CI ). Other sources of electromagnetic radiation such as high voltage lines, electrical machines, complex electrical environments, visual display terminals, or radar units were not associated with uveal melanoma. This is the first study describing an association between radiofrequency radiation exposure and uveal melanoma. Several methodologic limitations prevent our results from providing clear evidence on the hypothesized association. Mobile phone use, exposure to radiofrequency electromagnetic field, and brain tumour: a case control study T Takebayashi1, N Varsier2,3, Y Kikuchi1, K Wake3, M Taki2, S Watanabe3, S Akiba4 and N Yamaguchi*,5 1Department of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan; 2Department of Electrical and Electronic Engineering, Tokyo Metropolitan University, Tokyo, Japan; 3EMC Group, Applied Electromagnetic Engineering, National Institute of Information and Communications Technology, Tokyo, Japan; 4Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima; 5Department of Public Health, Tokyo Women s Medical University, Tokyo , Japan British Journal of Cancer (2008) 98, doi: /sj.bjc

16 In a case control study in Japan of brain tumours in relation to mobile phone use, we used a novel approach for estimating the specific absorption rate (SAR) inside the tumour, taking account of spatial relationships between tumour localisation and intracranial radiofrequency distribution. Personal interviews were carried out with 88 patients with glioma, 132 with meningioma, and 102 with pituitary adenoma (322 cases in total), and with 683 individually matched controls. All maximal SAR values were below 0.1Wkg_1, far lower than the level at which thermal effects may occur, the adjusted odds ratios (ORs) for regular mobile phone users being 1.22 (95% confidence interval (CI): ) for glioma and 0.70 ( ) for meningioma. When the maximal SAR value inside the tumour tissue was accounted for in the exposure indices, the overall OR was again not increased and there was no significant trend towards an increasing OR in relation to SAR derived exposure indices. A non significant increase in OR among glioma patients in the heavily exposed group may reflect recall bias. The effects of recall errors and of selection bias in epidemiologic studies of mobile phone use and cancer risk MARTINE VRIJHEIDa, ISABELLE DELTOURa, DANIEL KREWSKIa,b, MARIE SANCHEZa AND ELISABETH CARDISa ainternational Agency for Research on Cancer, Lyon, France bmclaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada Journal of Exposure Science and Environmental Epidemiology (2006) 16, doi: /sj.jes This paper examines the effects of systematic and random errors in recall and of selection bias in case control studies of mobile phone use and cancer. These sensitivity analyses are based on Monte Carlo computer simulations and were carried out within the INTERPHONE Study, an international collaborative case control study in 13 countries. Recall error scenarios simulated plausible values of random and systematic, non differential and differential recall errors in amount of mobile phone use reported by study subjects. Plausible values for the recall error were obtained from validation studies. Selection bias scenarios assumed varying selection probabilities for cases and controls, mobile phone users, and non users. Where possible these selection probabilities were based on existing information from non respondents in INTERPHONE. Simulations used exposure distributions based on existing INTERPHONE data and assumed varying levels of the true risk of brain cancer related to mobile phone use. Results suggest that random recall errors of plausible levels can lead to a large underestimation in the risk of brain cancer associated with mobile phone use. Random errors were found to have larger impact than plausible systematic errors. Differential errors in recall had very little additional impact in the presence of large random errors. Selection bias resulting from underselection of unexposed controls led to J shaped exposure response patterns, with risk apparently decreasing at low to moderate exposure levels. The present results, in conjunction with those of the validation studies conducted within the INTERPHONE study, will play an important role in the interpretation of existing and future case control studies of mobile phone use and cancer risk, including the INTERPHONE study.