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Title: Epidemiologic evidence for a relationship between NIR and cancer - a controversial issue


1
Epidemiologic evidence for a relationship between
NIR and cancer - a controversial issue
  • Michael KundiInstitute of Environmental Health,
    Medical University of Vienna, Austria

2
(No Transcript)
3
Power Frequency EMF and Cancer
  • Childhood leukemia 23 studies
  • Childhood nervous system tumors 11 studies
  • Other childhood cancers 8 studies
  • Adult leukemia 15 studies
  • Adult nervous system tumors 10 studies
  • Breast cancer 19 studies
  • Other adult cancers 4 studies

4
Childhood Leukemia
5
Power Frequency EMF and Cancer
The most comprehensively studied endpoint is
childhood leukemia. Pooled analyses (Ahlbom et
al. 2000 Greenland et al. 2000) demonstrate an
about two-fold increased risk at average exposure
of gt0.3 to 0.4 µT.
The International Agency for Research on Cancer
(IARC) classified power frequency magnetic fields
as a possible human carcinogen (Group 2B).
6
Can the relationship between childhood leukemia
and magnetic fields be causally interpreted?
  • Requirements
  • Temporal relation Exposure onset must be in line
    with what is known about the natural history of
    the disease
  • Association There must be a significant
    relationship between exposure and disease
  • Population equivalence Cohorts or cases as well
    as controls must be sufficiently similar (except
    for the exposure) to consider them equivalent
  • Environmental equivalence Cohorts or cases as
    well as controls must be exposed to the same
    environmental conditions (except for the exposure
    under study) to consider their environments
    equivalent

7
Equivocal support from animal studies due to
genetic factors?
Fedrowitz et al. 2004
8
Only about 1 of homes above 0.4 µT
9
Attributable risk
Source Kheifets et al. 2007
10
There is an increased risk of childhood leukemia
associated with power frequency magnetic fields
that is consistent with the natural history of
the disease.
In spite of the large number data base, some
uncertainty remains as to whether magnetic field
exposure or some other factor(s) might have
accounted for the increased leukaemia incidence.
(WHO Fact Sheet 263, 2001)
No confounder, neither selection nor
misclassification bias has been shown to explain
the relationship. Hence there are no valid
counterarguments against a causal interpretation.
There is no established mechanism of action and
animal as well as in vitro studies provide only
equivocal evidence for the carcinogenicity of
magnetic fields.
11
Lack of consistency of animal and in vitro
studies is rather the rule as the exception (e.g.
chlorinated hydrocarbons). Mechanism of action of
carcinogens is rarely known even if the agent has
been banned (e.g. chrysotile asbestos).
But the number of children exposed to levels
above 0.3 or 0.4 µT is very low and in a global
context, the impact on public health, if any,
would be limited and uncertain. (WHO EHC 238,
2007)
The attributable fraction is only low under the
assumption that there is a threshold and that the
average exposure level is the correct metric.
Provided that the health, social and economic
benefits of electric power are not compromised,
implementing very low-cost precautionary
procedures to reduce exposure is reasonable and
warranted. (WHO EHC 238, 2007)
12
Can the relationship between childhood leukemia
and magnetic fields be causally interpreted?
  • Requirements
  • Temporal relation Exposure was determined for
    residence at birth and at diagnosis?
  • Association There is a monotonous increase of
    risk for increasing levels of estimated exposure
    ?
  • Population equivalence Participation of controls
    was in some studies low with a potential for
    differential misclassification, however,
    comparison with studies based on registry data
    only showed the same effect size ?
  • Environmental equivalence Investigated
    confounders could not explain the observed
    increased risk ?

13
Summary
  • There is consistent evidence from epidemiological
    studies
  • Support from animal and in vitro studies is
    equivocal
  • There is no evidence based exposure metric
  • If there is a threshold at 0.3 to 0.4 µT
    attributable risk is low, however, data are
    consistent with a much higher attributable risk
    depending on the mechanisms of action
  • There are no valid counter arguments against a
    causal interpretation of the relationship between
    magnetic fields and childhood leukemia
  • Future studies must focus on the mechanism of
    action and the definition of a suitable evidence
    based exposure metric

14
Radiotelephones and Human Health - A European
Research Initiative A.F. McKinlay Radiation
Protection Dosimetry 72313-320 (1997) Whereas a
large database exists for possible effects on
human health from exposure to extremely low
frequency (particularly power frequency)
electromagnetic fields, there are far fewer data
for radiofrequency (including microwave) fields,
and very few related to the emissions and
exposures specific to personal telecommunications.
A comprehensive assessment of the risk of
effects on human health requires such data.
15
Epidemiological Studies of Mobile Phones and
Brain Tumors
16
COHORT OF MP USERS
Incidence of brain tumors 55000
5000
Relative Risk 55000/350001.67
COHORT OF NON-USERS
5000
Incidence of brain tumors 35000
17
BRAIN TUMOR CASES
Odds for MP use 520
Odds ratio 520/3221.83
CONTROLS
Odds for MP use 322
18
Overall 25 epidemiological studies published
19
Methodological Difficulties
  • If correctly applied, analytical epidemiology is
    able to detect a risk from an exposure provided
    the following conditions are met
  • There is a reliable exposure metric
  • There is an evidence based selection of a disease
  • Exposure duration is compatible with the natural
    history of the disease

None of these conditions are at present met for
the study of mobile phone use and tumors in the
head region.
20
Problem 1 Exposure Metric
21
Fundamental problems of exposure assessment
All these patterns have the same cumulative hours
of use!
Are they equivalent?
22
Problem 1 Exposure Metric
It is unknown which aspect of exposure is
responsible for the increased risk.
Cumulative hours of use, cumulative number of
calls, specific absorption rate in the area of
the tumor and other parameters may or may not
reflect essential aspects of exposure.
The mechanism of interaction between the EMF and
cells and tissues must be the basis for the
definition of exposure!
23
Problem 2 Selection of Disease
24
Intracranial Tumors
Exposure for traditional MP use is predominantly
to the head. Therefore, studies were almost
exclusively about tumors in the head region.
Nervous System Tumors
Neuroepithelial tissue Astrocytic tumors
(11) Oligodendroglial tumors (2) Mixed glioma
(2) Ependymal tumors (8) Choroid plexus
(2) Neuronal and mixed (12) Embryonal tumors
(11) Others (5)
Peripheral nerves Schwannoma (4) Neurofibroma Peri
neuroma MPNST (5)
Lymphoma Haematopoietic Neoplasms (3) Germ cell
(8) Sellar region (4)
Meningial Tumors Meningioma (16) Mesenchymal (21)
25
Molecular histopathology
Pluripotent Stem-cell
One and the same histopathologic type may be
distinctly different with respect
to molecular histopathology
Glioblastoma multiforme
26
Problem 2 Selection of Disease
Are all types of brain tumors associated with an
increased risk from mobile phone use?
It is impossible to differentiate all types of
tumors with respect to this risk based on
epidemiology!
It is important to work on potential mechanisms
of action of low intensities of EMF on biological
systems!
27
Problem 3 Exposure Duration
28
Is there any chance to find an increased risk for
even the strongest environmental carcinogen in
the short or medium term?
29
Latency of Brain Tumors
  • Glioma
  • 20-30 years average (Kranzinger et al. 2001
    Sadetzki et al. 2005)
  • Meningioma
  • 20-40 years average (Umansky et al. 2008)
  • Acoustic Neuroma
  • Average doubling time 1.7 years -gt 25 years
    Latency (Mohyuddin et al. 2003)

30
Interphone Study Exposure Duration
Source Hepworth et al. BMJ 2006
332(7546)883-887
31
Problem 3 Exposure Duration
Average exposure duration in epidemiological
studies conducted so far is 15 of latency
period!
If exposure duration is only a small proportion
of the natural history of the disease even potent
carcinogens are undetectable in epidemiological
studies!
Only those subgroups that use a mobile phone for
at least 10 years are relevant!
32
Exposure is predominantly unilateral!
97-99 of absorbed power from mobile phone use
is absorbed in the hemisphere corresponding to
the side of the head the mobile phone is held
during calls
Only the side of the head the phone is held to
during calls can be considered exposed!
The most important result from epidemiological
studies is the risk estimate associated with long
term ipsilateral mobile phone use!
33
Summary Glioma (gt10 years of MP use)
34
Summary Acoustic Neuroma (gt10 years of MP use)
35
Summary Meningioma (gt10 years of MP use)
36
Summary
Epidemiologic evidence indicates an increased
risk for mobile phone users to develop brain
tumors. Considering biases that could have had
distorted estimates, combined risks are rather
underestimates. For the time being epidemiology
provides the only consistent evidence for an
increased risk. Although support from other areas
of research is weak evidence is sufficient to
recommend precautionary measures to reduce
exposure.
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