Summary – Interphone Study Group – brain tumours

The Interphone study is the name given to a series of multi-national case-control studies to assess whether RF exposure from mobile phones is associated with cancer risk. The International Agency for Cancer Research (IARC) has coordinated the study. Other potential environmental and endogenous risk factors were also examined. The types of cancer studied were acoustic neuroma, glioma, meningioma, and tumours of the parotid gland. It is the largest epidemiological study to date and should help resolve some of the questions about an association between cell phones and cancer.

Participating countries were Australia, Canada, Denmark, Finland, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Sweden, and the UK. The principal investigators of the INTERPHONE study published a paper that provided details of the design and epidemiological methods, as well as a description of the population included in the study (Cardis et al., 2007). The population included 2,765 glioma, 2,425 meningioma, 1,121 acoustic neuroma, 109 malignant parotid gland tumour cases and 7,658 controls. The paper discussed potential recall and participation biases and their impact on the results. Others papers have also been published on (1) the validation of short term recall of mobile phone use for the Interphone study, (2) the effects of recall errors and of selection bias, (3) and the recall bias in the assessment of exposure to mobile phones from a retrospective validation study. A publication on the distribution of RF energy emitted by mobile phones in anatomical structures of the brain was also recently published in 2008(4).

Results of national studies have been published since 2004 and are summarized below in Tables (a,b,c). The combined analyses of the 13 countries participating in the INTERPHONE study have been finalized and the results are published in the International Journal of Epidemiology.

The Interphone study group is currently working on detailed analyses for future publications such as precise localization of brain tumours using 3-dimensional radiological grid, the health effect of radiofrequency exposure at the exact location of the tumor by using a gradient of radiofrequency. Determinants of mobile phone output power from a software-modified phone (SMP) study is also in preparation. Results from both the prospective and retrospective validation studies and also data obtained from the simulation study of recall and selection bias will help make any adjustment for exposure measurement errors on cancer risk related to mobile phone use.

More information can be obtained at www.iarc.fr - follow the links to "IARC Scientific Structure" and "Radiation Group".

The Tables summarise the INTERPHONE studies of brain tumours, including acoustic neuroma and tumours of the parotid gland. (For complete results of studies of brain tumours, see the main menu of "Epidemiology".)

a) Glioma

Name, site
Case
(participation rate %)
Controls
(participation rate %)
Age range
OR regular use
(95% IC)
OR = 10 yrs
Other
Christensen '05 Denmark
252 (71)
485 (64)
20-69
0.71 (0.50-1.01)
1.64 (0.44-6.12) - low grade tumours -6 cases
= 10 yrs - high grade 0.48 (0.19-1.26) - 8 cases
Lonn '05 Sweden
371 (74)
674 (71)
20-69
0.8 (0.6-1.0)
0.9 (0.5-1.5) - 25 cases
Parietal/temporal lobes 0.8 (0.6-1.1)
Schuz '06 Germany
366 (79.6)
732 (62.7)
30-69
0.98 (0.74-1.29)
2.20 (0.94-5.11) -12 cases
Cordless 0.93
Hepworth '06 UK
966 (51)
1716 (45)
18-69
0.94 (0.78-1.13)
0.90 (0.63-1.28) – 66 cases
Ipsilateral 1.24 (1.02-1.52) Contralateral 0.75 (0.61-0.93)
Klaeboe '07 Norway
289 (77)
358 (69)
19-69
0.6 (0.4-0.9)
0.6 (0.4-0.9)
Ipsilateral 1.0 (0.7-1.4)
Lahkola '07 Nordic countries combined
1521 (60)
3301 (50)
18-69
0.78 (0.7-0.9)
0.95 (0.74-1.23)
Ipsilateral ≥ 10 yrs 1.39 (1.01-1.92)
Hours '07 France
96 (60)
96 (74.7)
30-59
1.15 (0.65-2.05)
0
Ipsilateral 1.15 (0.55-2.43)
Takebayashi '08 Japan
83 (59)
196 (53)
30-69
1.22 (0.63–2.37)
0.58 (0.09–3.86)
Ipsilateral
1.24 (0.67–2.29) Contralateral
1.08 (0.57–2.03)
The INTERPHONE Study Group
2708 (64)
2972 (53)
30-59
0.81 (0.70-0.94)
0.98 (0.76-1.26)
Ipsilateral
0.84 (0.69-1.04)
Contralateral
0.67 (0.52-0.87)
Temporal lobe
0.86 (0.66-1.13)
Parietal or frontal lobes
0.77 (0.62-0.95)
Other locations
0.79 (0.51-1.23)


b) Meningioma

Name, site
Case
(participation rate %)
Controls
(participation rate %)
Age range
OR regular use
(95% IC)
OR = 10 yrs
Other
Christensen '05 Denmarke
175 (74)
316 (64)
20-69
0.83 (0.54-1.28)
1.02 (0.32-3.24)
Lonn '05 Swede
273 (85)
674 (71)
20-69
0.7 (0.5-0.9)
0.9 (0.4-1.9)
Schuz '06 Alemagne
381 (88.4)
762 (62.7)
30-69
0.84 (0.62-1.13)
1.09 (0.35-3.37)
Klaeboe '07 Norway
207 (71)
358 (69)
19-69
0.8 (0.5-1.1)
0
Hours '07
145 (78.4)
145 (74.7)
30-59
0.74 (0.43-1.28)
0
Ipsilateral 0.62 (0.32-1.20)

Takebayashi '08 Japan

128 (78)

279 (52)

30-69

0.70 (0.42–1.16)

1.35 (0.31–5.93)

Ipsilateral            1.14 (0.65–2.01) Contralateral        0.65 (0.37–1.13)

Lahkola '08 Nordic countries combined

1209 (74)

3299 (50)

20-69
18-59 (England)

0.76 (0.65-0.89)

0.85 (0.57-1.26)

Ipsilateral ≥ 10 yrs 0.99 (0.57-1.73)

The INTERPHONE Study Group
2409 (78)
2662 (53)
30-59
0.79 (0.68-0.91)
0.83 (0.61-1.14)
>Ipsilateral
0.86 (0.69-1.08)
Contralateral
0.59 (0.46-0.76)
Temporal lobe
0.55 (0.36-0.82)
Parietal or frontal lobes
0.79 (0.63-0.99)
Other locations
0.76 (0.56-1.04)


c) Acoustic neuroma

Name
Cases
OR Regular use
OR>5 yrs (95% OR)
OR>10 yrs (95% OR)
Comments
Christensen 2004
106
0.9
(n=17) 0.86
(n=2) 0.22
Ipsilateral use: OR =0.68
Lonn 2004
148
1.0
(n = 30) (5-9 yrs) 1.1
(n = 14) 1.9 (0.9-4.1)
Ipsilateral use: OR 1.1; for 5-9 yrs 1.1; for = 10 yrs 3.9 (1.6-9.5) Contralateral use: 0.9 for all durations
Schoemaker 2005
678
0.9
0.9
1.1 (0.7-1.8)
Ipsilateral use: OR = 0.9; for >10 years since first use, OR = 1.3; OR for >10 lifetime years of use = 1.8 (1.1-3.1)
Takebayashi 2006
101
0.73
(n=19) 1.09 (0.58-2.06)
(n=1)
Ipsilateral use: OR=0.9
Klaeboe 2007
45
0.5
(= 6 yrs)
(n = 7) 0.5 (0.2-1.5)
0
Ipsilateral use: OR = 0.7
Schlehofer 2007
97
0.67 (0.38-1.19)
(n=8) 0.53 (0.22-1.27)
0

OR for persistent noise exposure = 2.31 (1.15-4.66); for hay fever = 2.20 (1.09-4.45)

Hours '07
109 (80.7)
214 (74.7)
0.92 (0.53-1.59)
0
Ipsilateral 0.62 (0.32-1.20)


d) Tumours of the parotid gland

Author
# of cases
OR any use
OR>5
(95% CI)
OR>10
(95% CI)
Comment

Lonn '06 Sweden & Denmark

199

0.7malignant 0.9 benign 

0.7 malignant n=8)
0.9 benign (n=24)

0.3 malignant (n=1)

1.1 benign (n=5)
Ipsilateral use: OR=1.2  (0.6-2.6)

Sadetzki '08 Israel

460

1.06 malignant 0.85 benign

0.79 malignant  (n=12)
1.04 benign (n=129)

0.45 malignant (n=1)
1.02 benign (n=12)

Ipsilateral use: OR 1.01; 1.34 for 5 yrs; 1.69 for ≥ 10 yrs                           

Other Interphone publications:

Schuz (2006c) also investigated the association between exposure to the base stations of cordless phones and the risk of brain cancer. No increased risk was found.
The same group found no significant association between occupational exposure to radiofrequency/microwave EMFs and brain tumours (Berg, 2006).
Lonn (2006) found no increased risk of either benign or malignant parotid gland tumours, regardless of duration of use.

The Interphone study group carried out a validation study of short-term recall of phone use (Vrijheid 2006).  There were moderate to high correlations between recalled and actual use, as measured by operators or through the use of software modified phones.  The authors found that there was moderate systematic error and substantial random error. The latter error would tend to reduce the power of the Interphone study to detect an increase in brain tumour risk, if one exists.

Kan and colleagues performed a meta-analysis of 9 Interphone studies published between 2000 and 2006 (Kan et al., 2007). The 9 studies included a total of 5,259 cases of primary brain tumours and 12,074 controls. There was an overall Odds ratio (OR) of 0.90 (95% CI 0.81-0.99) for cell phone use and brain tumour development. The pooled OR for cell phone users of ≥ 10 years (5 studies) was 1.25 (95% CI 1.01-1.54).

Schlehofer et al. (2007) used Interphone data to analyze potential environmental risk factors for acoustic neuroma. While there was no risk for ionizing radiation or for cell phone use, they found increased risks for persistent noise and for hay fever history.

References:

The INTERPHONE Study Group. Brain tumour risk in relation to mobile telephone use: results of the INTERPHONE international case–control study. International Journal of Epidemiology 2010. Epub ahead of print, May 18, 2010

Berg G, Spallek J, Schuz J, Schlefor B, et al. (2006): Occupational exposure to radio frequency/microwave radiation and the risk of brain tumours: Interphone study group, Germany.
Am J Epidemiol 164:538-548.
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Cardis E, Richardson L, Deltour I, Armstrong B, and 44 others (2007): The INTERPHONE study: design, epidemiological methods, and description of the study population. Eur J Epidemiol DOI 10.1007/s10654-007-9152-z.

Cardis E, Deltour I, Mann S, Moissonnier M, Taki M,Varsier N, Wake K, Wiart J. (2008). Distribution of RF energy emitted by mobile phones in anatomical structures of the brain. Phys. Med. Biol. 53:2771–2783.

Christensen HC, Schuz J, Kosteljanetz M, Skovgard H, et al. (2004): Cellular telephone use and risk of acoustic neuroma. Am J Epidemiol 159:277-283
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Christensen HC, Schuz J, Kosteljanetz M, Skovgaard Poulsen H, et al. (2005): Cellular telephones and risk for brain tumours: A population-based, incident case-control study. Neurology 64:1189-1195.
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Hepworth SJ, Schoemaker MJ, Muir KR, Swerdlow AJ, et al. (2006): Mobile phone use and risk of glioma in adults: case-control study. BMJ (published online 20 January)
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Hartikka H,Heinävaara S,Mäntylä R, Kähärä V, Kurttio P, Auvinen A. Mobile phone use and location of glioma: A case-case analysis Bioelectromagnetics Jan 13, 2009 Ahead of print.

Hours M, Montestrucq L, Arslan M, Bernard M, El Hadjimoussa H, Vrijheid M, Deltour I, Cardis E. (2007): Validation des outils utilizes pour la mesure de la consommation téléphonique mobile dans l’étude INTERPHONE en France. Environnement, Risques & Santé 6(2):101-109

Hours M, Bernard M, Montestrucq L, Arslan M, et al. (2007): Téléphone mobile, risque de tumeurs cérébrales et du nerf vestibulaacoustique: l'étude cas-témojns INTERPHONE en France. (Cell phones and risk of brain and acoustic nerve tumours: the French INTERPHONE case-control study). Revue d'Épidémiologie et de Santé Publique 2007, doi: 10.10.16/j.respe.2007.06.002
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Kan P, Simonsen SE, Lyon JL, Kestle JRW (2007): Cellular phone use and brain tumor: a meta-analysis. J Neurooncol DOI 10.1007/s11060-007-9432-1
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Klaeboe L, Blaasaas KG, Tynes T (2007): Use of mobile phones in Norway and risk of intracranial tumours. Eur J Cancer Prev 16:158-164
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Lahkola A, Auvinen A, Raitanen J, Schoemaker MJ, et al. (2007): Mobile phone use and risk of glioma in 5 North European countries. Int J Cancer 120:1769-1775.
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Lahkola A, Salminen T, Raitanen J, Heinävaara S, Schoemaker M, Christensen HC, Feychting M, Johansen C, Klæboe L, Lönn S, Swerdlow A, Tynes T, Auvinen A. Meningioma and mobile phone use--a collaborative case-control study in five North European countries. Int J Epidemiol. Aug 2, 2008 Ahead of print.

Lonn S, Ahlbom A, Hall P, Feychting M (2004): Mobile phone use and the risk of acoustic neuroma. Epidemiology 15:653-659.
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Lonn S, Ahlbom A, Hall P, Feychting M, et al. (2005): Long-term mobile phone use and brain tumour risk. Amer J Epidemiol 161:526-535.
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Lonn S, Ahlbom A, Christensen HC, Johansen C, et al. Mobile phone use and risk of parotid gland tumor. Am J Epidemiol:2006;164:637-643.
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Sadetzki S, Chetrit A, Jarus-Hakak A, Cardis E, Deutch Y, Duvdevani S, Zultan A, Novikov A, Freedman L, Wolf M.  Cellular Phone Use and Risk of Benign and Malignant Parotid Gland Tumors—A Nationwide Case-Control Study American Journal of Epidemiology Ahead of print December 6, 2007

Schlehofer B, Schlaefer K, Blettner M, Berg G, et al. (2007): Environmental risk factors for sporadic acoustic neuroma (Interphone Study Group, Germany). Eur J Cancer 43:1741-1747.
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Schoemaker MJ, Swerdlow AJ, Ahlbom A, Auvinen A, et al. (2005): Mobile phone use and risk of acoustic neuroma: results of the Interphone case-control study in five North European countries. British Journal of Cancer 2005;93:842-848.
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Schuz J, Bohler E, Berg G, Schlehofer B, et al. (2006a): Cellular phones, Cordless phones, and the risks of glioma and meningioma (Interphone study group, Germany). Am J Epidemiol 163:512-520.
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Schuz J, Bohler E, Schlehofer B, Berg K, et al. (2006c): Radiofrequency electromagnetic fields emitted from base stations of DECT cordless phones and the risk of glioma and meningioma (Interphone study group, Germany). Radiat Res 166:116-119.
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Takebayashi T, Akiba S, Kikuchi Y, Taki M, et al. Mobile phone use and acoustic neuroma risk in Japan. Occup Environ Med: Published online 15 August 2006.
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Takebayashi T, Varsier N, Kikuchi Y, Wake K, Taki M, Watanabe S, Akiba S, Yamaguchi N. Mobile phone use, exposure to radiofrequency electromagnetic field, and brain tumour: a case-control study. Br J Cancer. 2008 98(3):652-659. Epub ahead of print Feb 5 2008. doi:10.1038/sj.bjc.6604214

Vrijheid M, Cardis E, Armstrong BK, Auvinen A, et al. (2006a): Validation of short term recall of mobile phone use for the Interphone study. Occup Environ Med 63:237-243.

Vrijheid M, Deltour I, Krewski D, Sanchez M, et al. (2006b): The effects of recall errors and of selection bias in epidemiologic studies of mobile phone use and cancer risk. Journal of Exposure Science and Environmental Epidemiology, advance online publication 14 June, 2006.

Vrijheid M, Armstrong BK, Bedard D, Brown J, Deltour E, Iavarone I, Krewski D, Lagorio S, Moore S, Richarson L, Giles G, McBride M, Parent M-E, Siemiatycki J, Cardis E. (2008): Recall bias in the assessment of exposure to mobile phones Journal of Exposure Science and Environmental Epidemiology 1–13.

Vrijheid M, Armstrong BK, Bédard D, Brown J, Deltour I, Iavarone I, Krewski D, Lagorio S, Moore S, Richardson L, Giles GG, McBride M, Parent ME, Siemiatycki J, Cardis E.(2009). Recall bias in the assessment of exposure to mobile phones. J Expo Sci Environ Epidemiol. 19, 369–381.

Vrijheid M, Mann S, Vecchia P, Wiart J, Taki M, Ardoino L, Armstrong BK, Auvinen A, Bédard D, Berg-Beckhoff G, Brown J, Chetrit A, Collatz-Christensen H, Combalot E, Cook A, Deltour I, Feychting M, Giles GG, Hepworth SJ, Hours M, Iavarone I, Johansen C, Krewski D, Kurttio P, Lagorio S, Lönn S, McBride M, Montestruq L, Parslow RC, Sadietzki S, Schüz J, Tynes T, Woodward A, Cardis E.(2009). Determinants of mobile phone output power in a multinational study – implications for exposure assessment. Occup Environ Med. 66(10):664-71.

Vrijheid M, Richardson L, Armstrong BK, Auvinen A, Berg G, Carroll M, Chetrit A, Deltour I, Feychting M, Giles GG, Hours M, Iavarone I, Lagorio S, Lönn S, McBride M, Parent ME, Sadetzki S, Salminen T, Sanchez M, Schlehofer B, Schüz J, Siemiatycki J, Tynes T, Woodward A, Yamaguchi N, Cardis E. (2009). Quantifying the impact of selection bias caused by nonparticipation in a case-control study of mobile phone use. Ann Epidemiol 19(1):33-41.

 

 

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