Gliom-Inzidenzraten in den nordischen
Ländern im Kontext möglicher
Mobilfunk-assoziierter Risiken

Dr Joachim Schüz, Dr Isabelle Deltour
Head, Environment and Lifestyle Epidemiology BranchÜbersicht
Evidenz epidemiologischer Studien:• Kohortenstudien aus Dänemark und Großbritannien mit Hunderttausenden vonTeilnehmern zeigen keine erhöhten Gliom-Risiken
aber: keine Expositionsdaten um besonders häufige Nutzer separat zu analysieren• Einige Fallkontrollstudien zeigen keinen ebenfalls keinen Zusammenhangaber: meist Studien von vor dem Jahr 2000, so dass Nutzungszeit eher kurz war• Eine multinationale und eine frz. Studie zeigen moderat erhöhtes Gliom-Risiko unterden häufigsten Nutzern (<5% der Studienpopulation)
aber: Hinweise, dass der Zusammenhang ein statistisches Artefakt sein könnte
• Eine Studienserie in Schweden zeigt ein generell erhöhtes Gliom-Risiko
aber: schon mit früheren Inzidenzstudien als widersprüchlich eingestuft
Hypothese:
Weil Handy-Nutzung so weit verbreitet ist, müssten sich die in den epidemiologischenStudien beobachteten erhöhten Risiken in den entsprechenden Risikogruppen über die
Zeit durch einen messbaren, kompatiblen Anstieg der Gliom-Inzidenzrate zeigen

Data for Incidence Analyses• Data on number of cases from population based cancer registries in Denmark,Finland, Norway and Sweden• 28,015 male and 20,630 female primary glioma cases• Aged 20 to 84 years old• Diagnosed between 1979 and 2016
• Population data from population registries (5 year age groups)• Total person-years: 663 million• E.g., 2016: 1,724 observed cases in 19.7 million 20-84 years old• Annual age standardised incidence rates (European standard)• Time trends: Joinpoint regression models allowing for changes in time trends

Age-specific glioma incidence rates
IR / 100,000; Nordic countries

Men

Women

2520
15
10521
1979 1984 1989 1994 1999 2004 2009 2014 1979 1984 1989 1994 1999 2004 2009 2014

Year
Observed 70-84 years
Observed 40-59 years
Fitted values

Observed 60-69 years
Observed 20-39 years

Summary Incidence Analysis• Updated previous analyses (1979-2008) of Nordic glioma incidence rates (IR) by 8
additional years of data
• No modification of long term time trends in IR of glioma in last decades of observation• Overall, in ages < 59 years, IR were relatively stable• Increases in IR in ages 60-69 years, and in 70-84 yrs
 Improved access to improved diagnosis tools Improved registration of cancer cases (Denmark, Norway) Increased tendency to perfom biopsies (oligodendroglioma, treatment guidelines) Changes in risk factors?

Methods Simulation Study• There are epidemiological studies of case-control design which reported
elevated risks associated to use of mobile phone• We created risk scenarios with a range of at-risk groups, and risk levels, basedon risks reported in those studies
Men 40-59 yrs old: APC=0.1 (0.0; 0.3) [1979-2016]
Men 60-69 yrs old: APC=0.6 (0.4; 0.9) [1979-2016]• Evidence: No effect-measure modification of risk by age• In Hardell et al, 2015, those aged 20-49 and 50+ at first use of mobile phone had the samerisk increase• In Coureau et al, 2014, higher associations were observed for 30–59-years-old subjects,
compared to 18-29 and 60+.
• In Interphone, 2010, there was no appreciable effect modification by age or sex in any of
the glioma results

6

Identification ofreference

Period of caserecruitment

Hardell and Carlberg 1997-1999,(Pathophysiology,2000-2003 and2015)2007-2009

Cerenat study(Coureau et al, OEM, 2004–2006
2014)

Interphoneinternational study
2000-2004(13 countries)(IJE, 2010)
Interphone-Canada(Moioli et al, AJE,2001-2004
2017)

Size of case-control study

1498 malignant brain tumour
cases;
risk analysis on 1380 glioma
cases and 3430 controls

253 gliomas cases and 892
matched controls

Age atExposure definition
diagnosis

18–80

16 +

OR

95% CIuse of mobile phones morethan one year

1.3

1.1 to 1.6

10 to 15 years after firstusing a mobile phone (higherrisks reported for persons
exposed longer)

1.4

1.1 to 1.9

self-reported lifetime
cumulative mobile phone
conversations ≥ 339 hours

1.78

0.98 to 3.24

self-reported lifetime
cumulative mobile phone
conversations ≥896 hours

2.89

1.41 to 5.93

1.40

1.03 to 1.89

2.0

1.2 to 3.4

2708 gliomas cases and 2972
matched controls

30-59

self-reported lifetime
cumulative mobile phone
conversations ≥1640 hours

170 gliomas cases and 653
controls

30-59>558 hours of cumulative
hours of use

Modelling prevalence of regular mobile phone users
Regular users in men 40-59 years old

90

90

80

80

7060
50
4070
60
50
40

30302020

10100
1979

1984

1989

1994

1999

2004

Regular users in men 60-69 years old

100

Fraction of population (%)

Fraction of population (%)

1002009

2014

01979

1984

Cosmos Denmark

19941999

2004

2009

2014

YearYear
Nordic interphone1989

Cosmos France

Nordic interphone

Cosmos Denmark

Cosmos France

8

SIR Analysis in 40-59 year old men
350
300
250

250

300

350

Risk scenario: RR=1.1, all users at risk after an induction period

10 yrs

200

200

5 yrs
1980

1990

2000
year

Observed

2010

2020

1980

Expected

1990

2000
year

Observed

2020

Expected

300
250

250

300

350

Exp. if no risk

350

Exp. if no risk

2010

20 yrs200

200

15 yrs
1980

1990

2000
year

Observed
Exp. if no risk

2010
Expected

2020

1980

1990

2000year

Observed
Exp. if no risk

2010
Expected

2020

Exposure distribution ofNordic Interphone controls;
0.5 IR increase explainedSIR results in men 40-59 years oldAt risk group

All mobile phone users
5 yrs lag

10 yrs lag

15 yrs lag

20 yrs lag

Hypothetical RR

SIR

95%CI

SIR

95% CI

SIR

95%CI

SIR

95% CI

2.5

0.6(0.59 ; 0.62)

0.69(0.67 ; 0.70)

0.79(0.78; 0.81)

0.91(0.90 ; 0.93)

20.7(0.69 ; 0.71)

0.77(0.76 ; 0.78)

0.85(0.84; 0.87)

0.94(0.93 ; 0.96)

1.5

0.83

(0.81; 0.84)

0.87(0.86 ; 0.89)

0.93(0.91; 0.94)

0.98(0.96; 1.00)

1.4

0.86

(0.84; 0.87)

0.9(0.88 ; 0.92)

0.94(0.92; 0.96)

0.98(0.96 ; 1.00)

1.3

0.89

(0.88; 0.91)

0.92(0.91 ; 0.94)

0.96(0.94; 0.98)

0.99(0.97 ; 1.01)

1.2

0.93

(0.91; 0.95)

0.95(0.93 ; 0.97)

0.98(0.96; 0.99)

1.00(0.98 ; 1.02)

1.1

0.97

(0.95; 0.99)

0.98(0.96 ; 1.00)

0.99(0.97; 1.01)

1.00(0.99; 1.02)

1.08

0.98

(0.96; 1.00)

0.99(0.97 ; 1.01)1.00(0.98; 1.02)

1.01(0.99 ; 1.03)

1.05

0.99

(0.97; 1.01)

1.00(0.98 ; 1.02)

1.00(0.98; 1.02)

1.01(0.99; 1.03)

Exposure distribution ofNordic Interphone controls;
0.5*IR increase explainedSIR results in men 60-69 years oldAt risk group

All mobile phone users
5 yrs lag

10 yrs lag

15 yrs lag

20 yrs lag

Hypothetical RR

SIR

95% CISIR

95% CISIR

95% CISIR

95% CI

2.5

0.68(0.67 ; 0.70)

0.73(0.72 ; 0.75)

0.84(0.82 ; 0.86)

0.97(0.95 ; 0.99)

2.00.78(0.76 ; 0.80)

0.83(0.81 ; 0.84)

0.91(0.89 ; 0.93)

1.01(0.99 ; 1.03)

1.5

0.91

(0.89 ; 0.93)

0.94(0.92 ; 0.96)

0.99(0.97 ; 1.02)

1.05(1.03 ; 1.08)

1.4

0.94

(0.92 ; 0.97)

0.97(0.95 ; 0.99)

1.01(0.99 ; 1.04)

1.06(1.04 ; 1.09)

1.3

0.98

(0.96 ; 1.00)

1.00(0.98 ; 1.02)

1.03(1.01 ; 1.06)

1.07(1.05 ; 1.10)

1.2

1.02

(0.99 ; 1.04)

1.03(1.01 ; 1.05)

1.05(1.03 ; 1.08)

1.08(1.06 ; 1.10)

1.1

1.06

(1.03 ; 1.08)

1.06(1.04 ; 1.09)

1.08(1.05 ; 1.10)

1.09(1.07 ; 1.11)

1.08

1.06

(1.04 ; 1.09)

1.07(1.05 ; 1.10)

1.08(1.06 ; 1.11)

1.09(1.07 ; 1.12)

1.05

1.08

(1.05 ; 1.10)

1.08(1.06 ; 1.11)

1.09(1.06 ; 1.11)

1.09(1.07 ; 1.12)

Exposure distribution of
Nordic Interphone controls;
0.5*IR increase explainedIdentification ofreference
Hardell and Carlberg(Pathophysiology,2015)

Cerenat study(Coureau et al, OEM,2014)-Interphone (Canada)(Momoli et al, AJE,2017)
Interphoneinternational study(13 countries) (IJE,2010)

Age atExposure definition
diagnosis

18–80

16 +30-59

30-59

OR

95% CI

Compatibility with main SIR Analysis

1.3

1.1 to 1.6

Not compatible

1.4

1.1 to 1.9

Not compatible

1.78

0.98 to 3.24

Not compatible

self-reported lifetime
cumulative mobile phone
conversations ≥896 hours

2.89

1.41 to 5.93

Not compatible for 40-59 years

self-reported lifetime
cumulative mobile phone
conversations >558 hours

2.0

1.2 to 3.4

use of mobile phones morethan one year
10 to 15 years after firstusing a mobile phone (higherrisks reported for persons
exposed longer)
self-reported lifetime
cumulative mobile phone
conversations ≥ 339 hours

self-reported lifetime
cumulative mobile phone
conversations ≥1640 hours

Not compatible for 40-59 years
Not compatible for 40-59 years

1.4

1.03 to 1.89

Compatible when assuming risk only
related to GSM MP generation

Diskussion
Zeitliche Trends in der Gliom-Inzidenz widersprechen einem Einfluss durch Mobilfunk:• Anstieg bei 70-84-Jährigen vor der weiten Verbreitung Mobilfunk• Anstieg bei 60-69-Jährigen zu konstant für Einfluss Mobilfunk• Kein oder fast kein Anstieg bei den JüngerenZeitliche Trends bei Männern und Frauen zu ähnlich, was Einfluss durch MobilfunkwidersprichtÜberprüfung mit epidemiologischen Studien zeigen dass die in den Fallkontrollstudien
beobachteten Risikoerhöhung nicht mit den tatsächlichen Inzidenzen an Gliomen bei
Männern kompatibel sind
• Ausnahme: Interphone 13-Länder-Studie wenn nur Risikoerhöhung durch NMT/GSMTechnologien angenommen aber nicht ab UMTS oder Risiko wurde überschätztLatenzzeiten >20 Jahre, Risiken nur in Subgruppen oder kleine Risiken (<10%) sind miteinem derartigen ökologischen Analyse-Ansatz nicht auszuschließen

Co-authors
Aslak Harbo Poulsen, Danish Cancer Society Research Center,Copenhagen, Denmark
Christoffer Johansen, Rigshospitalet, Copenhagen, Denmark
Anssi Auvinen, University of Tampere, Finland
Tom Børge Johannesen, The cancer registry of Norway, Oslo,
NorwayMaria Feychting, Karolinska Institutet, Stockholm, Sweden
The Cancer Registries of the Nordic countriesFunding: Bundesamt für Strahlenschutz, FM 8867

IARC ENV Activities on RF
Funded by

INTER-CAL
Funded by

GliMoRi
Funded byFunded byCohort Study of Mobile Phone Users:
300,000+ MP Users followed up for various outcomes inDenmark, Finland, Sweden, The Netherlands, the UK andin France (by IARC); 1st Cancer FU in 2022
Modelling Study of INTERPHONE:
Is the J-shape relationship between MP use and glioma aresult of an interplay of various biases?; final report June
Consistency check; publication under review
Update of theUK Million Women
Cohort Study:
No association;
Published March