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From: [e-mail] (John Moulder)
Newsgroups: sci.med.physics,sci.answers,news.answers
Subject: Powerlines and Cancer FAQs (2 of 4)
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Date: 25 Mar 1994 18:03:03 GMT
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Summary: Q&As on the connection between powerlines, electrical
  occupations and cancer (continued)
Keywords: powerlines, magnetic fields, cancer, EMF, non-ionizing
  radiation, FAQ
Xref: bloom-beacon.mit.edu sci.med.physics:1293 sci.answers:1012 news.answers:16848

Archive-name: powerlines-cancer-FAQ/part2
Last-modified: 1994/3/25
Version: 2.4

FAQs on Power-Frequency Fields and Cancer (part 2 of 4)

16) What do laboratory studies tell us about power-frequency fields and
cancer?

Carcinogens, agents that cause cancer, are generally of two types:
genotoxins and promoters.  Genotoxic agents (often called initiators)
directly damage the genetic material of cells.  Genotoxins usually effect
all types of cells, and may cause many different types of cancer.
Genotoxins generally do not have thresholds for their effect; in other
words, as the dose of the genotoxin is lowered the risk gets smaller, but
it never goes away.  A promoter (often called an epigenetic agent) is
something that increases the cancer risk in animals already exposed to a
genotoxic carcinogen.  Promoters usually effect only certain types of
cells, and may cause only certain types of cancer.  Promoters generally
have thresholds for their effect; in other words, as the dose of the
promoter is lowered a level is reached in which there is no risk.

16A) Are power-frequency fields genotoxic?

There are many approaches to measuring genotoxicity.  Whole-organism
exposure studies can be used to see whether exposure causes cancer or
causes mutations.  Cellular studies can be done to detect DNA or
chromosomal damage.

Very few whole-organism exposure studies have been done.  Bellossi et al
[G13] exposed leukemia-prone mice for 5 generations and found no effect on
leukemia rates; however, since the study used 12 and 460 Hz pulsed fields
at 60 G (6 mT), the relevance of this to power-frequency fields is unclear.
 Otaka et al [G18] showed that power-frequency magnetic fields did not case
mutations in fruit flies.  Rannug et al [G19] found that power-frequency
magnetic fields did not increase the incidence of skin tumors or leukemia
in mice.  RD Benz et conducted a multi-generation mouse exposure study in
1983-1985 as part of the NY State Powerlines Project; this study reported
no increase in mutations rates or sister chromatid exchanges, but has never
been published.

A number of published laboratory studies have reported that power-frequency
magnetic fields do not cause DNA strand breaks [G4,G16] chromosome
aberrations [G1,G6,G15], sister chromatid exchanges [G2,G6,G11,G20],
micronuclei formation [G9,G11] or mutations [G3,G15,G17].

Many of the above laboratory studies also examined power-frequency
electrical fields and combination of power-frequency electrical and
magnetic fields [G1,G2,G4,G8,G11,G16].  As with the studies of magnetic
fields alone, the studies of electrical fields and combined fields showed
no evidence of genotoxicity.

There are two positive reports of genotoxicity.  Khalil & Qassem [G12]
reported that a 10.5 G (1.05 mT) pulsed field caused chromosome
aberrations.  Nordenson et al [E4] reported that switchyard workers exposed
to spark discharges had an increased rate of chromosomal defects, but
Bauchinger et al [E2] for no such increase in chromosomal defects in a
similar study.

16B) Are power-frequency magnetic fields cancer promoters?

There are agents (for example, promoters) that influence the development of
cancer without directly damaging the genetic material.  It has been
suggested that power-frequency EMFs could promote cancer [L1].  In a
promotion test, animals are exposed to a known genotoxin at a dose that
will cause cancer in some, but not all animals.  Another set of animals are
exposed to the genotoxin, plus another agent.  If the agent plus the
genotoxin results in more cancers that seen for the genotoxin alone, then
that agent is a promoter.

Published studies have shown that power-frequency magnetic fields do not
promote chemically-induced skin cancer [G10,G14,G19] or chemically-induced
liver cancers [G21,G24].  For chemically-induced breast cancer, one study
has shown promotion [G22] and one has not [G23].

16C) Do power-frequency magnetic fields enhance the effects of other
genotoxic agents?

There are some other types of studies that are relevant to the carcinogenic
potential of agents, but that are not strictly either genotoxicity or
promotion tests. The most common of these are cellular studies that test
whether an agent enhances the genotoxic activity of a known genotoxin;
these studies are the cellular equivalent of a promotion study.

Published studies have reported that power-frequency magnetic fields do not
enhance the mutagenic effects of known genotoxins [G3,G9], and do not
inhibit the repair of DNA damage induced by ionizing [G7,G8] or UV [G15]
radiation.

One study [G6] has reported that power-frequency fields can increase the
frequency of sister chromatid exchanges induced by known genotoxins.

17) How do laboratory studies of the effects of power-frequency fields on
cell growth, immune function, and melatonin relate to the question of
cancer risk?

There are other biological effects that might be related to cancer.  There
are substances (called mitogens) that cause non-growing normal cells to
start growing.  Some mitogens appear to be carcinogens.  There have been
numerous studies of the effects of power-frequency fields on cell growth
(proliferation) and tumor growth (progression). Most recent studies of the
effects of power-frequency magnetic fields on cancer progression have shown
no effect [G5,G10,H3], but one has reported enhanced progression [G14].
Most recent studies of effects of power-frequency magnetic fields on cell
growth have also shown no effect [G1,G11,G16,G20,H2,H7,H8], but some have
shown increased [G6] or decreased [G12] cell growth.  With one possible
exception [H1] there have been no reported effects on proliferation or
progression for fields below 2000 mG (200 microT).

Suppression of the immune system in animals and humans is associated with
increased rates of certain types of cancer, particularly lymphomas [E6,E7].
 Immune suppression has not been associated with excess leukemia and brain
cancer.  Some studies have shown that power-frequency fields can have
effects on cells of the immune system [K2], but no studies have shown the
type or magnitude of immunosuppression that is associated with increased
cancer risks.

It has also been suggested that power-frequency EM fields might suppress
the production of the hormone melatonin, and that melatonin has
"cancer-preventive" activity [H6,H7,L2].  This is highly speculative.
There have been some reports that EM fields effect melatonin production,
but studies using power-frequency magnetic fields have not shown
reproducible effects [H9,H10].  In addition, while there is some evidence
that melatonin has "cancer-preventive" activity against transplanted breast
tumors in rats, there is no evidence that melatonin effects other types of
cancer, or that it has any effect on breast or other cancers in humans.

18) Do power-frequency fields show any effects at all in laboratory
studies?

While the laboratory evidence does not suggest a link between
power-frequency magnetic fields and cancer, numerous studies have reported
that these fields do have "bioeffects", particularly at high field strength
[H4,H5,K1,K2].  Power-frequency fields intense enough to induce electrical
currents in excess of those that occur naturally (above 5 G, 500 microT,
see Question 8) have shown reproducible effects, including effects on
humans [K1].

Below about 2 G (200 microT) there are few published (and replicated)
reports of bioeffects, although there are unreplicated reports of effects
for fields as low as about 200 mG (20 microT). Even among the scientists
who believe that there may be a connection between power-frequency fields
and cancer, there is no consensus as to mechanisms which would connect
these "bioeffects" with cancer causation [K1,L1].

19) What about the new "Swedish" study showing a link between power lines
and cancer?

There are new residential and occupational studies from Sweden
[C12,C17,D7], Denmark [D9,C15], Finland [C14] and the Netherlands [C16].
The published studies are considerably more cautious in their
interpretations of the data than were the unpublished preliminary reports
and the earlier press reports.

The authors of the Scandinavian childhood cancer studies [C14,C15,C17] have
produced a collaborative meta-analysis of their data [B6].  The RRs
(Question 13) from this meta-analysis are shown below in comparison to
meta-analysis of the prior studies [B4,B5].
Childhood leukemia, Scandinavian:    2.1 (1.1-4.1)
Childhood leukemia, prior studies:   1.3 (0.8-2.1)
Childhood lymphoma, Scandinavian:    1.0 (0.3-3.7)
Childhood lymphoma, prior studies:   none
Childhood CNS cancer, Scandinavian:  1.5 (0.7-3.2)
Childhood CNS cancer, prior studies: 2.4 (1.7-3.5)
All childhood cancer, Scandinavian:  1.3 (0.9-2.1)
All childhood cancer, prior studies: 1.6 (1.3-1.9)

- Fleychting & Ahlbom [C12,C17].  This is a case-control study of everyone
who lived within 300 meters of high-voltage powerlines between '60 and '85.
 For children all types of tumors were analyzed; for adults only leukemia
and brain tumors were studied.  Exposure was assessed by spot measurements,
calculated retrospective assessments, and distance from power lines.  No
increased overall cancer incidence was found in either children or adults,
for any definition of exposure.  An increased incidence of leukemia (but
not other cancers) was found in children for calculated fields over 2 mG
(0.2 microT) at the time of diagnosis, and for residence within 50 m (150
ft) of the power line.  The increased incidence of leukemia is found only
in one-family homes; there is no increased incidence in apartments.  The
retrospective fields calculations do not take into account sources other
the transmission lines.  No significant elevation in cancer incidence was
found for measured fields.

- Verkasalo et al [C14].  This is a cohort study of cancer in children in
Finland living within 500 m of high-voltage lines.  Only calculated
retrospective fields were used to define exposure.  The calculated fields
are based only on lines of 110 kV and above and do not take into account
fields from other sources such as distribution lines, household wiring or
appliances. Both average fields and cumulative fields (microT - years) were
used as exposure metrics.  The total incidence of childhood cancer was not
significantly elevated for average exposure above 0.20 microT (2 mG), or
for cumulative exposure above 0.50 microT-years (5 mG-years).  A
significant excess incidence of brain cancer was found in boys; the excess
was due entirely to one exposed boy who developed three independent brain
tumors.  No significant increase in incidence was found for brain tumors in
girls or for leukemia, lymphomas or other cancers in either sex.

- Olsen and Nielson [C15].  This is a case-control study based on all
childhood leukemia, brain tumors and lymphomas diagnosed in Denmark between
'68 and '86.  Exposure was assessed on the basis of calculated fields over
the period from conception to diagnosis.  No overall increase in cancer was
found when 0.25 microT (2.5 mG) was used as the cut-point to define
exposure (as specified in the study design).  After the data were analyzed,
it was found that the overall incidence of childhood cancer was
significantly elevated if 0.40 microT (4 mG) was used as the cut-point.  No
significant increase was found for leukemia or brain cancer incidence for
any cut-point.  A significant increase in lymphoma was found for the 0.10
microT cut-point but not for higher cut-points.

- Guenel et al [D9].  This is a case-control study based on all cancer in
actively employed Danes between '70 and '87 who were 20-64 years old in
'70.  Each occupation-industry combination was coded on the basis of
supposed 50-Hz magnetic field exposure.  No significant increases were seen
for breast cancer, malignant lymphomas or brain tumors.  Leukemia incidence
was significantly elevated among men in the highest exposure category;
women in similar exposure categories showed no increase in leukemia.

-Floderus et al [D9].  This is a case-control study of leukemia and brain
tumors in occupationally-exposed men who were 20-64 years of age in '80.
Exposure calculations were based on the job held longest during the 10-year
period prior to diagnosis.  Many measurements were taken using a person
whose job was most similar to that of the person in the study. About
two-thirds of the subjects in the study could be assessed in this manner.
A significant elevation in incidence was found for leukemia, but not for
brain cancer.

-Schreiber et al [C16].  This is a retrospective cohort study of people in
an urban area in the Netherlands.  People were considered exposed in they
lived within 100 m of transmission equipment (150 kV lines plus a
substation).  Fields in the "exposed" group were 1-11 mG (0.1-1.1 microT),
fields in the "unexposed" group were 0.2-1.5 mG (0.02-0.15 microT).  The
total cancer incidence in the ╥exposed╙ group was insignificantly less than
that in the general Dutch population.  No cases of leukemia or brain cancer
were seen in the "exposed" group.

20) What criteria do scientists use to evaluate all the confusing and
contradictory laboratory and epidemiological studies of power-frequency
magnetic fields and cancer?

There are certain widely accepted criteria that are weighed when assessing
such groups of epidemiological and laboratory studies.  These are often
called the "Hill criteria" [E1].  Under the Hill criteria one examines the
strength (Question 20A) and consistency (Question 20B) of the association
between exposure and risk, the evidence for a dose-response relationship
(Question 20C), the laboratory evidence (Question 20D), and the biological
plausibility (Question 20E).  These criteria are viewed as a whole; no
individual criterion is either necessary or sufficient for concluding that
there is a causal relationship between an exposure and a disease.

Overall, application of the Hill criteria shows that the current evidence
for a connection between power-frequency fields and cancer is quite weak,
because of the weakness and inconsistencies in the epidemiological studies,
combined with the lack of a dose-response relationship in the human
studies, and the negative laboratory studies.

20A) Criterion One: How strong is the association between exposure to
power-frequency fields and the risk of cancer?

The first Hill criterion is the *strength of the association* between
exposure and risk.  That is, is there a clear risk associated with
exposure?  A strong association is one with a RR (Question 13) of 5 or
more.  Tobacco smoking, for example, shows a RR for lung cancer 10-30 times
that of non-smokers.

Most of the positive power-frequency studies have RRs of less than two.
The leukemia studies as a group have RRs of 1.1-1.3, while the brain cancer
studies as a group have RRs of about 1.3-1.5.  This is only a weak
association.

20B) Criterion Two: How consistent are the studies of associations between
exposure to power-frequency fields and the risk of cancer?

The second Hill criterion is the *consistency* of the studies.  That is, do
most studies show about the same risk for the same disease?  Using the same
smoking example, essentially all studies of smoking and cancer showed an
increased risk for lung and head-and-neck cancers.

Many power-frequency studies show statistically significant risks for some
types of cancers and some types of exposures, but many do not.  Even the
positive studies are inconsistent with each other.  For example, while a
new Swedish study [C17] shows an increased incidence of childhood leukemia
for one measure of exposure, it contradicts prior studies that showed an
increase in brain cancer [B4,B5], and a parallel Danish study [D9] shows an
increase in childhood lymphomas, but not in leukemia.  Many of the studies
are internally inconsistent.  For example, where a new Swedish study [C17]
shows an increase for childhood leukemia, it shows no overall increase in
childhood cancer, implying that the rates of other types of cancer were
decreased.  In summary, few studies show the same positive result, so that
the consistency is weak.

20C) Criterion Three: Is there a dose-response relationship between
exposure to power-frequency fields and the risk of cancer?

The third Hill criterion is the evidence for a *dose-response
relationship*.  That is, does risk increase when the exposure increases?
Again, the more a person smokes, the higher the risk of lung cancer.

No published power-frequency exposure study has shown a dose-response
relationship between measured fields and cancer rates, or between distances
from transmission lines and cancer rates.  The lack of a relationship
between exposure and increased cancer incidence is a major reason why most
scientists are skeptical about the significance of the epidemiology.

Not all relationships between dose and risk can be described by simple
linear no-threshold dose-response curves where risk is strictly
proportional to risk.  There are known examples of dose-response
relationships that have thresholds, that are non-linear, or that have
plateaus.  For example, the incidence of cancer induced by ionizing
radiation in rodents rises with dose, but only up to a certain point;
beyond that point the incidence plateaus or even drops.  Without an
understanding of the mechanisms connecting dose and effect it is impossible
to predict the shape, let alone the magnitude of the dose-response
relationship.

20D) Criterion Four: Is there laboratory evidence for an association
between exposure to power-frequency fields and the risk of cancer?

The fourth Hill criterion is whether there is *laboratory evidence*
suggesting that there is a risk associated with such exposure?
Epidemiological associations are greatly strengthened when there is
laboratory evidence for a risk.  When the US Surgeon General first stated
that smoking caused lung cancer, the laboratory evidence was ambiguous.  It
was known that cigarette smoke and tobacco contained carcinogens, but no
one had been able to make lab animals get cancer by smoking (mostly because
it is hard to convince animals to smoke).  Currently the laboratory
evidence linking cancer and smoking is much stronger.

Power-frequency fields show little evidence of the type effects on cells,
tissues or animals that point towards their being a cause of cancer, or to
their contributing to cancer (Question 16).

20E) Criterion Five: Are there plausible biological mechanisms that suggest
an association between exposure to power-frequency fields and the risk of
cancer?

The fifth Hill criterion is whether there are *plausible biological
mechanisms* that suggest that there should be a risk?  When it is
understood how something causes disease, it is much easier to interpret
ambiguous epidemiology.  For smoking, while the direct laboratory evidence
connecting smoking and cancer was weak at the time of the Surgeon Generals
report, the association was highly plausible because there were known
cancer-causing agents in tobacco smoke.

From what is known of power-frequency fields and their effects on
biological systems there is no reason to even suspect that they pose a risk
to people at the exposure levels associated with the generation and
distribution of electricity.

21) If exposure to power-frequency magnetic fields does not explain the
residential and occupations studies which show increased cancer incidence,
what other factors could?

There are basically four factors that can result in false associations in
epidemiological studies: inadequate dose assessment (Question 21A),
confounders (Question 21B), inappropriate controls (Question 21C), and
publication bias (Question 21D).

21A) Could problems with dose assessment affect the validity of the
epidemiological studies of power lines and cancer?

If power-frequency fields are associated with cancer, we do not know what
aspect of the field is involved.  At a minimum, risk could be related to
the peak field, the average field, or the rate of change of the field.  If
we do not know who is really exposed, and who is not, we will usually (but
not always) underestimate the true risk [C13].

21B) Are there other cancer risk factors that could be causing a false
association between exposure to power-frequency fields and cancer?

Associations between things are not always evidence for causality.  Power
lines (or electrical occupations) might be associated with a cancer risk
other than magnetic fields.  If such an associated cancer risk were
identified it would be called a "confounder" of the epidemiological studies
of power lines and cancer.  An essential part of epidemiological studies is
to identify and eliminate possible confounders.  Many possible confounders
of the powerline studies have been suggested, including PCBs, herbicides,
traffic density, and socioeconomic class.

- PCBs: Many transformers contain polychlorinated biphenyls (PCBs) and it
has been suggested that PCB contamination of the power-line corridors might
be the cause of the excess cancer.  This is unlikely.  First, PCB leakage
is rare.  Second, PCB exposure has been linked to lymphomas, not leukemia
or brain cancer.

- Herbicides: It has been suggested that herbicides sprayed on the
powerline corridors might be a cause of cancer.  This is an unlikely
explanation, since herbicide spraying would not effect distribution systems
in urban areas (where 3 of 5 positive childhood cancer studies have been
done).

- Traffic density: Transmission lines frequently run along major roads, and
the "high current configurations" associated with excess childhood leukemia
in the US studies [C1,C6,C10] are associated with major roads.  It has been
suggested that power lines might be a surrogate for exposure to
cancer-causing substances in traffic exhaust.  This may be a real
confounder, since traffic density has been shown to correlate with
childhood leukemia incidence [E5].  Note that this would explain only the
residential connection, not the occupational connection.

- Socioeconomic class: Socioeconomic class may be an issue in both the
residential and occupational studies, as socioeconomic class is clearly
associated with cancer risk, and "exposed" and "unexposed" groups in many
studies are of different socioeconomic classes [C13].  This is of
particular concern in the US residential exposure studies that are based on
"wirecoding", since the type of wirecodes that are correlated with
childhood cancer are found predominantly in older, poorer neighborhoods,
and/or in neighborhoods with a high proportion of rental housing [C18].

21C) Could the epidemiological studies of power lines and cancer be biased
by the methods used to select control groups?

An inherent problem with many epidemiological studies is the difficulty of
obtaining a "control" group that is identical to the "exposed" group for
all characteristics related to the disease except the exposure.  This is
very difficult to do for diseases such as leukemia and brain cancer where
the risk factors are poorly known.  An additional complication is that
often people must consent to be included in the control arm of a study, and
participation in studies is known to depend on factors (such as
socioeconomic class, race and occupation) that are linked to differences in
cancer rates.  See Jones et al [C18] for an example of how selection bias
could effect a powerline study.

21D) Could analysis of the epidemiological studies of power lines and
cancer be skewed by publication bias?

It is a known that positive studies in many fields are more likely to be
published than negative studies (see Dickersin et al [E3] for examples from
cancer clinical trials).  This can severely bias meta-analysis studies such
as those discussed in Questions 13 and 15.  Such publication bias will
increase apparent risks.  This is a bigger potential problem for the
occupational studies than the residential ones.  It is also a clear problem
for laboratory studies -- it is much easier to publish studies that report
effects than studies that report no effects (such is human nature!).

Several specific examples of publication bias are known in the studies of
electrical occupations and cancer (see Doll et al [B5], page 94).  In their
review Coleman and Beral [B2] report the results of a Canadian study that
found a RR of 2.4 for leukemia in electrical workers.  The British NRPB
review [B5] found that further followup of the Canadian workers showed a
deficiency of leukemia (a RR of 0.6), but that this followup study has
never been published.  This is an anecdotal report, but publication bias,
by its very nature, is usually anecdotal.

22) What is the strongest evidence for a connection between power-frequency
fields and cancer?

The best evidence for a connection between cancer and power-frequency
fields is probably:
a) The four epidemiological studies that show a correlation between
childhood cancer and proximity to high-current wiring [C1,C6,C10,M2], plus
the meta-analysis of the Scandinavian studies [B6].
b) The epidemiological studies that show a significant correlation between
work in electrical occupations and cancer, particularly leukemia and brain
cancer [B1,B2,D7,D9].
c) The lab studies that show that power-frequency fields do produce
bioeffects.  The most interesting of the lab studies are probably the ones
showing increased transcription of oncogenes at fields of 1-5 G (100-500
microT) [H4,H5,L1].
d) The one laboratory study that provides evidence that power-frequency
magnetic fields can promote chemically-induced breast cancer [G22].

23) What is the strongest evidence against a connection between
power-frequency fields and cancer?

The best evidence that there is not a connection between cancer and
power-frequency fields is probably:
a) Application of the Hill criteria (Question 20) to the entire body of
epidemiological and laboratory studies.
b) The fact that all studies of genotoxicity, and all but one study of
promotion have been negative (Question 16).
c) Adair╒s [F4] biophysical analysis that indicates that "any biological
effects of weak (less than 40 mG, 4 microT) ELF fields on the cellular
level must be found outside of the scope of conventional physics"
d) Jackson╒s [E8] and Olsen╒s [C15] epidemiological analysis that shows
that childhood and adult leukemia rates have been stable over a period of
time when per capita power consumption has risen dramatically.

24) What studies are needed to resolve the cancer-EMF issue?

In the epidemiological area, more of the same types of studies are unlikely
to resolve anything.  Studies showing a dose-response relationship between
measured fields and cancer incidence rates would clearly affect thinking,
as would studies identifying confounders in the residential and
occupational studies.

In the laboratory area, more genotoxicity and promotion studies may not be
very useful.  Exceptions might be in the area of cell transformation, and
promotion of chemically-induced breast cancer. Long-term rodent exposure
studies (the standard test for carcinogenicity) would have a major impact
if they were positive, but if they were negative it would not change very
many minds.  Further studies of some of the known bioeffects would be
useful, but only if they identified mechanisms or if they established the
conditions under which the effects occur (e.g., thresholds, dose-response
relationships, frequency-dependence, optimal wave-forms).

25) Is there any evidence that power-frequency fields could cause health
effects other than cancer.

While this FAQ sheet, and most public concern, has centered around cancer,
there has also been suggestions that there might be a connection between
non-ionizing EM exposure and birth defects.  This concern has focused as
much on video display terminals (VDTs) as on power lines.  Little
epidemiological or laboratory support for a connection between non-ionizing
EM exposure and birth defects has been found. [J1,J2,J4,J5,J6].  Cox et al
[J3] and Chernoff et al [K5] have recently reviewed this field.

End:  powerlines-cancer-FAQ/part2