RADIATION
INDUCED CANCER IN HUMANS
A Study Guide: Issues & data analysis
Summary of the work of John W. Gofman, MD,PhD
By Gary Evans, MD
PURPOSE
To discuss the cancer risks associated
with commonly used medical diagnostic x-ray exposures. The study
of radiation induced cancer brings many groups to the table. These
include the D.O.E. with interest in nuclear materials manufacturing,
storage, shipping and waste management, the D.O.D. with interest
in nuclear weapons manufacturing, storage, and deployment, and the
nuclear power industry (GE, Westinghouse, etc.) who have major financial
incentives to develop and export nuclear technologies. The DOE and
the GAO estimated in the late 1980's that nuclear site cleanup will
total between 63 and 175 billion dollars [NYT-88, NYT-89]. If radiation
risk estimates are increased, the cost of cleanup will increase
dramatically as will the cost of radiation protection in general
- recently estimated at $2000.00 per exposure rem [H.Phys1997].
The overall dollars involved are estimated to be over a trillion
when plutonium trade and reactor exports are considered. Past low
radiation risk estimates & statements of threshold or even beneficial
effects of irradiation have been all but discarded by most committees
as new data has become available. Whether the 3 mile island & Cherobyl
disasters and the subsequent decreased public tolerance for reactor
construction, waste processing and storage has played a roll in
data acquisition and analysis is an interesting and open question..
Agencies involved include: NCRP, BEIR, UNSCEAR, IRCP, NRC, RERC,
IEA, EPA, and groups of independent scientists.
ORGANIZATION
OF DISCUSSION
Radiation basics:
Units of radiation exposure;
High vs. low LET radiation; X-ray energy content,generation;
Biologic response to radiation: Mutagenesis; Adaptive responses
Calculation: Radiation induced cancer rate per radiation dose.
* Mathematics of risk: Relative vs. absolute
* Shape of Dose-Response Curve: Linear vs. linear-quadratic vs. quadratic
(Concave UP or DOWN)
* Threshold level of low dose radiation exposure and cancer induction
* Risk at low doses and dose rates vs. high acute doses.
[DREF's - dose rate effectiveness factor]
* Radiosensitivity to cancer induction with respect to age and sex.
* Duration of excess cancer risk
Application of risks derived from one population to another population.
Risk assessments applied to common medical X-ray exams.
[Radionuclides, RBE factors for neutron and alpha emitters, etc. not discussed]
PHYSICAL DEFINITIONS AND PROPERTIES OF RADIATION
(Definitions of Ionizing Particles)
Alpha : Helium nuclei = 2 protons, 2 neutrons;
Range in tissues 30-40:m (< sheet of paper) but intensely damaging.
[KeV-MeV] : Enormous collision energy deposited along short track
leaving great damage to localized area (High LET).
Beta : Nuclear electron ejected at high
speed; Range in tissues a few millimeters. [KeV-MeV]
Neutron : Neutral particle with high LET
but not as interactive as Alpha; Produced in nuc. disint.(key to chain
reactions) [KeV-MeV]
Gamma : Photons generated in nuclear decay;
Penetrating, less interactive w/ matter (Low LET) [KeV-MeV]
X-ray : Photons of lower energy than gamma,
generated the atomic electron cloud level; [med=KeV] : Penetrate tissues
similar to gamma radiation but recent evidence of 2x the risk of cancer
induction over gamma.
UV : Photons of lower energy than X-Ray
and Gamma, but ionizing level; Less penetrating than X-Ray or Gamma.
[>4.13eV]
-- Photons below ionization energy: Visible
[1.77 - 4.13 eV], IR [10-3 eV], microwaves [10-5 eV], radiowaves [10-10
eV] --
UNITS
OF RADIATION
Based on Energy deposition per mass of
target [KE= ½ mv2 - for equal KE radiation,heavier particle moves
proportionately slower]
ROENTGEN: 1 electrostatic unit of charge/0.001293
gms air (0 deg.C & 760mmHg) = 83 ergs/gm air = 93 ergs /gm tissue
RAD: 10-5 joules per gram of material irradiated
= 102 ergs per gram = 6.24 x 1010 KeV per gram
Note - Typical biochemical bond broken
by 5-7 eV and electron ionized off of hydrogen atom by 13.6eV. 1
rad of radiation = 4.59 x 1012 tissue ionizations [2.08 x 109 photons/rad
x30KeV/photon/13.6eV/H-ion] 1 PA CXR (6 yo) = 15 mrad = 6.9 x 1010
tissue ionizations [3.12 x 107 photons/15mrad x30KeV/photon/13.6eV/H-ion]
REM: "Roentgen equivalent man" - RAD x RBE
in human RBE = Exp. & theoretical relative biologic effectiveness
of given radiation type. [Relative to gamma: Alpha ~ 10-20x, Neutron
~1-10x, X-ray=2x]
ENERGY DEPOSITION: Whatever the type and/or
source of radiation, when a beam passes through tissues a track of
ionized atoms is generated via the stripping off of electrons from
their orbits - resulting in broken chemical bonds. Those initially
freed electrons then move off at high speed & collide w/ other atoms
causing further ionizations. In this way a cascade of electrons (&
broken bonds) percolate through the irradiated tissue until finally
most of the energy is absorbed in new, often aberrant, chemical bonds.
Most of the total number of X-ray photons generated by diagnostic
machines are absorbed; only a small fraction are required for collision
w/ the detector or film. [Note: Med. X-rays absorbed via Compton scattering
&/or photoelectric effect w/ lower energy photons (mammography 25-27
KeV) absorbed predominantly by the photoelectric mechanism resulting
in electrons w/ higher LET (more dangerous) than are generated by
higher energy X-ray photons].
BJR89
TRACK CALCULATION FOR TYPICAL 90 KEV X-RAY BEAM:
1 rad of low LET radiation: deposition
of 10-5 Joules / gram of tissue = 6.24 x 1010 KeV/gm Medical X-ray
typically 90KeV peak = 30KeV average photon. [RADPRT81, RADPRT83]
à (6.24 x 1010 KeV/gm) / (30KeV/photon) = 2.08 x 109 photons/gm Range
of 30KeV photons in tissue = 19.779m = 1.735 cells traversed per initial
photon à (2.08 x 109 photons/gm) x (1.735 cells traversed/photons)
= 3.61 x 109 cells traversed/gm Nucleus is ~ 0.25 of volume of cell
à (3.61 x 109 cells traversed) x (0.25 nuclei volume / cell volume)
= 9.03 x 108 nuclear volumes tracked / gm There are 6.75 x 108 nuclei
per gram of tissue à (9.03 x 108 nuclear vol's traversed / gm) / (6.75
x 108 nuclei./gram) = 1.3378 nuclear tracks / nucleus [at 1 rad] à
Dose resulting in one nuclear track (on average) per initial photon
= (1/1.3378) x (1 rad) = 747.5 mrad Poisson distribution: At 750 mrad:
1 nuclear track (on average) / nucleus are actually distributed as
follows: 37% will have no tracks, 37% will have single tracks, and
26% will have two or more tracks Chem. bonds are broken by 5-7 eV
collisions:For 30KeV photons: 30KeV/6eV = 5000 bonds broken/init.photon
[max]. à Thus a typical 90 KeV diagnostic X-ray machine yielding a
tissue dose of 750 mrad will generate up to ~ 5000 broken bonds in
2/3'rds (Poisson distribution) of ~ 109 nuclei per gram of tissue
irradiated. BIOLOGIC EFFECTS OF LOW DOSE EXPOSURE, DNA
DNA DAMAGE
- MALIGNANCY
MATH:
Dosimetry; Linearity vs. quadratic vs.
linear-quadratic; DDREF's, Adaptation kinetics; Threshold vs. no threshold;
Latency (genomic instability); Duration of risk Relative vs. absolute;
Effect of age, sex, other factors (smoking)
DNA DAMAGE:
Ionizing radiation results in the freeing
of electrons from target atoms. These travel at extremely high speeds
and occasionally strike a critical region of DNA and if accurate repair
is ineffective, cancer is one possible result. The common DNA lesions
documented can be grouped into the following: [see also Jeggo PA]
* SSB: Linear w/ dose. Unusual end groups unlike physiol. oxidation lesions [Ward 1990]
* DSB Repair mech. error prone [GOF-90][Ward1988][Pfeiffer1998]
* DNA-PROTEIN X LINKS Error prone repair [see p3 NCRP draft]
* MULTIPLY DAMAGED SITES Error prone repair [see p3 NCRP draft]
"Ionizing radiations produce many different possible clusters
of spatially adjacent damage, & analysis of track structures
from different types of radiation has shown that clustered DNA
damage of severity at least >/= double strand breaks can occur
at biologic relevant frequencies at any dose."
[Brenner&Ward1992] Other ref's:[Goodhead1994][Hei,et.al.1997]
The susceptibility to these lesions has
been found (in vitro) to depend on cell type, on cell cycle phase,
etc. Spont. rate of cell lesions ~24,000/cell/d [Helbock et al 1998];
these oxid. lesions are easily/accurately repaired [Ward 85,'95]
SUMMARY:
A 90KeV (peak) X-ray beam delivering a
750 mrad tissue dose will result in electron tracks through a large
majority of cellular nuclei along the beam path (37% of nuclei w/
1 trk.+26% nuclei w/ 2-3 trks). This causes breakage of up to 5000
bonds / ave.nucleus. The true ave. collision = 60 ev or 8-10 x that
needed for simple bond breakage; the energy remaining is kinetic causing
physical disruption after breakage. Repeat radiation exposures generate
additive statistical risks of non-repairable or mis-repaired lesions
occurring in critical DNA regions. Many studies have now demonstrated
<100% DNA repair at moderate & low doses. Radiation induced cancer
has been documented to follow multiple low (average of < 1 trk/nucl.)
doses of medical X-ray irradiation given over time frames greater
than the known DNA repair mechanisms which are completed in times
of several minutes to 8 hours.
DNA DAMAGE -> GENOMIC
INSTABILITY:
Mouse cells irradiated in vitro, placed
into host mouse - no tumors created. If instead, post irradiated cells
are grown to approx. 30 generations then injected into host animal,
tumors result. This is not true for control cells not irradiated but
grown in vitro in the same way. "The loss of stability of the genome
is becoming accepted as one of the most important aspects of carcinogenesis."
… "One of the hallmarks of the cancer cell is the inherent instability
of the genome." [Morgan 1966 p247 and p254]. Other ref's:[Nowell 976]
[Cheng1993] [Kadhim1992,1994,1995] [Holmberg1994] [Marder1993] [Mendonca1993]
[Kronenberg1994] [Ullrich1998] "… Instead, initiation [of cancer]
more likely appears to be an event that increases the genomic instability
of the cells of subsequent rounds of cell division." [BEIR V p138]
MONOCLONAL SOLID TUMOR
ORIGIN:
Evidence is now quite strong that all cancers
are monoclonal in origin - i.e. one transformed cell is the initial
cause of all cancers. [Wainscoat & Frey 1990] [Worsham et al 1996]
[Nowell 1976] [Noguchi 1992] [Fialkow 1976, 1984] [Arnold et al 1983]
[Cleary et al 1988] [Levy et al 1977] [Minden et al 1985] [Evans 1979]
[Lloyd 1988]
DISEASES ASSOCIATED WITH
INABILITY TO REPAIR DNA LESIONS:
There are a variety of enzymes responsible
for DNA lesion repair. Several diseases are associated with increased
cancer risk and are known to have poorly functioning DNA repair systems
[Borek1983] [Chan1987] [Willis1987] [Cleaver1968] [Hecht1987] [Khan
SG1998] [Kikpi MO] [Groisman1999] [Becker1998]
Examples of diseases associated with an
increase in malignancy risk:
* Ataxia Telangiectasia Synd.: Double Strand DNA break repair mechanism defect
* Coccayne's Synd.: TCR (transcription coupled repair enzyme)[Cooper et al 1997]
* Nonpolyposis Colorectal CA: Mismatch repair enzyme system
* Blooms syndrome DNA: ligase repair enzyme defect
* Xeroderma pigmentosum: DNA excision repair mechanism defect
* Hepatitis B: Hep.B Virus X protein interferes w/ DNA repair mechanism -> hepatic CA.
RELATIVE
(MULTIPLICATIVE) RISK
Many studies have now convincingly shown
that cancer incidence each year post-irradiation increases at a rate
related to the spontaneous cancer rate, specific for age & population.
E.g.: if colon cancer incidence rates increase each year through life
then in an irradiated group, the incidence rate will increase faster
than the control, non irradiated group. The higher rate is equal to
a multiplier of the spontaneous rate; this is what is meant by relative
risk increase following irradiation. For radiation-induced cancer,
relative risk analysis is the accepted mathematical model. [GOF-81,90][BEIR-V][NCRP98],
etc.
SHAPE
OF DOSE : RESPONSE RELATIVE RISK CURVE
This is a debated issue. Some studies are
consistent with a linear dose-response curve [RERF91][RERF92], whereas
other studies are consistent with supralinear responses (larger effect
at low doses than at high doses) [GOF-81,90]. This remains an open
question. In terms of age at exposure, the data is clear that relative
risk is much higher at younger ages at irradiation. [Gof-Tam '69,'70][NCRP98][BEIR
V] [Most reasonable to consider dose-response curve as either linear
or supralinear (convex up);exercise due caution until more is known.
NO-THRESHOLD
FOR RADIATION INDUCED CANCER
Most radiation researchers agree that based
on current data there is likely to be no low-dose threshold for cancer.
Unlike chemical toxins which when given in sufficiently low doses
are detoxified or removed before damage is done, radiation is delivered
on the cellular level by high speed electrons that literally crash
through the cellular machinery. Many of the lesions that occur are
repaired by cellular mechanisms (estimated repair events number 10,000
-24,000 / cell per day). If, however, a high speed electron, set in
motion by a medical X-ray photon, collides with a critical portion
of DNA and repair systems are unable to properly undo the damage,
a malignancy may result. [UNSCEAR 1993 Rpt, p.634, para.74][NCRP98
draft rpt] Furthermore, even if it is postulated that double track
events are required for misrepair -- at any dose, the Poisson distribution
insures that some nuclei are hit by more than 1 track at a dose that
is calculated to deliver an average of much less than or equal to
one track through an average nucleus [i.e. <<750mrad]. As one single
track can damage the DNA, there is no theoretical threshold of risk
- i.e. As the dose decreases, the only change is in the number of
targets struck but at any dose at least one target may be hit and
may then generate a lesion leading to malignancy. With reference to
adaptive effects, experimental evidence suggests that at least 500
mrad is required and that this results in only a 50% reduction in
lesions. Repair mechanisms are therefore unable to fully protect at
any dose level. Thus, there is no theoretical basis for belief in
a threshold dose below which no sustained damage could occur. [NCRP98]
DURATION
OF INCREASE IN EXCESS RELATIVE RISK AFTER RADIATION EXPOSURE
Several studies, including those listed
in this paper continue to demonstrate that radiation induced excess
cancer rates continue for at least 40 years after exposure and perhaps
for a lifetime. The A-Bomb survivors, now 54 years after their exposure,
continue to show excess cancer rates. A-Bomb survivors have also been
shown to continue to carry chromosome abnormalities for at least 40
years after the exposure with dose dependent numbers of abnormalities
documented. [GOF-81 ->A-Bomb data, Hempleman 1975, Shore 1977, Boice-Monson
1977, etc.] The peak incidence rate for solid cancers (non-hematologic)
appears to occur at 30-40 years post irradiation. [GOF-90] "In contrast
to the rates for leukemia & bone cancer, the rates for most other
cancers appear to have remained in excess for as long as most exposed
populations have been followed" [BEIR V p52] A possible explanation
for ~ 10 year latencies seen for solid tumors: A single cell is critically
irradiated, resulting in genomic instability. Assuming no immune killing
effects, after >30 gen.'s the cell mass = 109 (1gm) -1012 (1 kg) cells.
With immune killing and suppression there would be long cancer latencies
& incidence durations from the initial damage.
EFFECT OF AGE AND SEX ON RADIATION SENSITIVITY - CANCER INDUCTION
Gofman's findings (A-Bomb study as well as meta-analysis of multiple studies)
Several studies [eg. RERF91a, see refs]
have also shown that children are more radiation sensitive than are
adults. This increased sensitivity follows the relative risk model,
i.e. after irradiation in childhood, the risk of cancer induction
20-40 years later is higher than if the same irradiation occurred
in adulthood with cancers detected 20-40 years later in older age.
Although risk per dose is proportionately
higher as age decreases, overall risk from medical diagnostic X-rays
works out to be highest at ages between 5-10 years, as between these
years the entrance dose grows faster than the relative risk of cancer
falls as the child ages.
ORGAN
SPECIFIC CANCER RATES FOLLOW RELATIVE RISK MODEL
Organs that have the highest malignant
transformation potential include: mouth, chest, abdomen, Pelvis. Several
studies: [eg. RERF90a, RERF94] have demonstrated that radiation induced
excess cancer risk is related to the baseline risk rate (organ specific
relative risk). If a particular organ is more likely to generate a
cancer than another organ, when both are exposed to the same radiation
dose, the increase in cancer rates of each will be proportional to
the respective organ specific unexposed, spontaneous cancer rate.
BIOLOGIC EFFECTS OF LOW DOSE EXPOSURE, ADAPTIVE RESPONSE
THE HISTORY OF "DDREFS"
There has been a question as to whether
a difference exists in cancer induction risk from acute delivery of
a low radiation dose compared with fractionated, low delivery rate
of a low total radiation dose. With animal based evidence only, a
mathematical construct, "Dose and Dose Rate Effectiveness Factor"
(DDREF) was created in the mid 1970's [UNSCEAR-77]. The logic for
its initial use has been sited over the past 20 years despite increasingly
conflicting human data. The current NCRP DRAFT (NCRP-98) report on
Low Dose Radiation Effects makes a very strong case against the use
of DDREF's or any other method that yields a non linear curve with
lower effects at low doses. In fact there is now data suggesting a
supralinear response with higher radiation induced cancer rates from
low doses than from high dose exposure. [GOF-81, GOF-90]. In reference
to low dose rate effects, there is a paucity of data to date. [Little
1999][Brenner 1999]
BEIR-V
CONFLICTING REFERENCES:
"In spite of evidence that the molecular
lesions which give rise to somatic and genetic damage can be repaired
to a considerable degree, the new data do not contradict the hypothesis,
at least with respect to cancer induction and hereditary genetic effects,
that the frequency of such effects increases with low-level radiation
as a linear, non-threshold function of the dose." [pg 4.] but then
on pg.6: "For low LET radiation, accumulation of the same dose over
weeks or months, however, is expected to reduce the lifetime risk
appreciably, possibly by a factor of 2 or more." "For most other cancers
in the LSS (A-Bomb Life Span Study), the quadratic contribution is
nearly zero, and the estimated DREF's are near unity. Nevertheless,
the committee judged that some account should be taken of dose rate
effects and in chapter 1 suggests a range of dose rate reduction factors
that may be acceptable." (pg.17) [see Tbl 1-4 "Summary of Dose Rate
Effectiveness Factors for Low-LET Radiation" and on page 22: "There
are scant human data that allow an estimate of the dose-rate effectiveness
factor (DREF)"
MOST
RECENT NCRP DRAFT REPORT:
"At the outset, it must be noted that radiation
imparts its energy to living matter through a stochastic process,
such that a single ionizing track has a finite probability of depositing
enough energy in traversing a cell to damage a critical molecular
target within the cell, such as DNA. Furthermore, the various types
of DNA damage that are known to result from irradiation appear to
increase linearly with the dose in low-to-intermediate dose range.
Also, although most such DNA damage is reparable to varying degrees,
some types of lesions - namely, double-strand breaks and multiply
damaged sites - are often repaired through a process that is error-prone.
Because of the vast number of target cells, vanishingly small frequencies
of non-lethal, unrepaired or misrepaired lesions can nevertheless
result in a finite number of cells undergoing a cancer-initiating
event, even at low doses." [NCRP-Oct.98 p228] "Those lesions in DNA
that remain unrepaired or are misrepaired may be expressed initially
in the form of mutations, the frequency of which increases with the
dose of radiation over the dose range in which the effects are amenable
to measurement. Although the shape of the dose-response curve varies,
depending on the LET of the radiation, the dose rate, the type of
mutation, and other variables, it is noteworthy that mutation of types
implicated in carcinogenesis - namely, point mutations and partial
deletion mutations - have been observed to be inducible at relatively
low doses, with apparently linear - nonthreshold dose-response relationships
in various kinds of cells." … AND … pg. 229 "Thus, the data imply
that traversal of the cell nucleus by a single low-LET radiation track
may occasionally suffice to cause a chromosome aberration." Referring
to a graph of excess relative risks established for solid tumor incidences,
researchers at RERF stated: "…clearly indicate that only LDEF [DDREF]
values near 1 are consistent with the shape of the dose-response curve
for solid tumor incidence. This suggests that a linear model provides
a good description of these data and that no low-dose correction is
needed." [RERF Update 4(3):5-6,1992] SUMMARY: Human data (& logic)
are consistent w/ a linear dose-response curve at low doses & dose
rates w/ some data consistent w/ supralinearity - i.e higher risks
per rad at lower doses and/or dose rates than high and/or acute doses.
CRITICAL ANALYSIS AND CRITICISM OF BEIR V METHODOLOGIES
Summary of work of John Gofman, MD, PHD [GOF-90][GOF-96]
PROCEDURES THAT DIRECTLY UNDERESTIMATE
RISK
1. Reliance on animal data The BEIR V report
(p.22) states: "There are scant human data that allow an estimate
of the dose-rate effectiveness factor." In its Executive Summary,
however, the committee recommends use of a DREF (Dose and Dose Rate
Effectiveness Factors) of at least two for environmental and occupational
exposures with the evidence based largely on animal model experiments.
This is the opposite of a conservative approach - that is, if one
assumes that the data base (animal) is questionable, one should not
decrease the assessed risk assessment applied to people. (DREF's lower
the calculated radiation risk, based on the rate that doses are delivered
- assuming that more slowly over time are less risky. The human data
suggesting this is very unconvincing. Waldren C, et al; "Measurement
of low levels of x-ray mutagenesis in relation to human disease";
Proc Natl Acad Sci USA 83: 4839-44 (1986) Found that conventional
methods for measuring mutagenesis in mammalian cells seriously underestimated
the contribution of radiation to cancer and genetic diseases. They
found a 200 fold higher mutation frequency in the 0-50rad range then
some previous conventional studies had found. They also found the
curve of dose:mutation to be supra-linear.
Little, JB; "Low-Dose Radiation Effects:
Interactions and Synergism" Health Phys 59: 49-56 (1990) Found significant
differences with regard to inhibitory effects of DMSO, dose response
and the effects of changes in dose-rate for radiogenic induction
of mutations in rodent, compared with human cells. He found reduced
effects in rodent cells when the dose was delivered at low rates
but at high total doses, but did not find these effects in human
cells between doses of 0-250rads. Thus the use of rodent cells to
infer human cellular response is questionable.
Carnes BA, Fritz TE; "Responses of the
beagle to protracted irradiation" Rad Res 128:125-32 (1991) 378
beagle dogs with accumulated doses between 450 and 3000 rads at
varying rates between 3.8 and 26.3 rads/day showed no relationship
between tumor mortality and dose rate but a clear linear relation
with accumulated dose.
2. Discarding data The BEIR V report also
discards data with little scientific basis for doing so. For example,
a.) cancer deaths in A-bomb survivors over 75 years old are discarded
owing to uncertainties of proper ascertainment of cause of death and
b) breast cancer rates following fluoroscopic irradiation in women
with tuberculosis were 6x higher in the Nova Scotia group than in
another Canadian study group - they therefore chose to discard that
data: "Within the Canada-TB cohort, the estimated risk per Gray for
women treated in Nova Scotia was about six times that for women treated
in other provinces. This difference is highly significant (p<0.001)
… the higher risk observed among Nova Scotia women is not attributable
to non-linearities in the dose response. Since there is currently
no explanation for thedifference within the Canadian-TB cohort and
since the Committee was generally interested in low dose effects,
it was decided to use the data on the Canadian-TB cohort without the
Nova Scotia women, as the basis for risk estimates in the parallel
analysis" [BEIR-V p255][see also GOF-96]
CRITICISMS OF RERF - IMPROPER HANDLING OF A-BOMB DATA
[1986 REFR COHORT CHANGES DISPUTED]
IMPROPER, NONBLINDED ALTERATION OF DOSE
GROUP COHORTS:
After the 1982 analysis, RERF shifted
thousands of people from one cohort to another in developing the
new dosimetry. Those who worked on revising the dosimetry had knowledge
of expected results therefore the change did not occur under blinded
conditions. In addition, in 1986 RERF added 11,393 Nagasaki survivors
who were exposed at a distance of 2500 to 9999 meters from the hypocenter
and for whom complete follow-up during 1950 - 1982 was available.
These 11,393 people were assigned to the 0 dose group to increase
the precision of the background mortality rate estimates and consequently
the excess risk estimates in Nagasaki. Again this was done in a
non-blinded fashion. In 1987 the cohort was changed from 91,231
to 75,991 with 15,240 persons moved into suspension as the corrections
made from the T65DR dosimetry to the DS86 dosimetry was not possible
given a lack of relevant information. (This is 31% of the Hiroshima
Dose-Group 2 cohorts!). The remaining 75,991 was denoted as the
DS86 cohort group. Because of this nonblinded alteration of dosimetry
and cohort status, Gofman chose to analyze the available data of
all survivors through 1982 (37 years after the bombings) for analysis
in his 1990 report.
COHORTS IMPROPERLY CONFIGURED - NOT AGE
(ATB) AND SEX MATCHED
Therefore even without irradiation, risk
of cancer and leukemia are different for these groups. The Gofman
analysis removes this bias by reconfiguration of cohorts of dose
groups. In the Gofman analysis, the only variable is therefore irradiation
dose. Raw RERF data is not properly normalized for age & sex (groups
must be equal to properly evaluate rad effect) Age Normalization:
* RERF Ref. grps 1+2 used as model for all other dose grps (male
& female) using ratio of each age band : total * From Table 11-D
rows 17-21: Age bands 1-5 -- ratios: 0.180, 0.193, 0.241, 0.230,
0.156 respectively are used (Total # in each dose band) x (Approp.
ratio above). Enter # as the norm'ed # in each age band for that
dose. * Recalc. Observations: (Norm'ed # people / raw # people)
x (raw observed #) = Norm'ed observations. * Recalc. Total observations
for each dose group. Sex Normalization: * Use ratio found in reference
group 1+2 (Tables 11-B,D Col's F where M/F = 27585/38443 = 0.717556)
* Find total people in dose group - eg. Grp.1: (15,406 M + 21,767
F = 37,173). * Let F = age and sex norm'ed #females in Grp.1. Then
0.717556 x F is age and sex normed #males in Grp1 * F + 0.717556*F
= 37,173 which is equiv. To 1.717556 * F = 37,173. Therefore F =
37,173/1.71756. * M=37,173 - F or M=37,173 - 37,173/1.71756 = 15,530.02
persons to enter into row 11G, Col.F (Row132) * Using same calculation,
enter norm'ed numbers for each dose group after which all dose groups
are norm'ed. * Recalc. Observations: (Norm'ed # people / raw # people)
x (raw observed #) - Norm'ed observations.
DS86 DOSIMETRY Several dosimetry systems
since the A-Bomb study began in 1950 as new information has been
discovered. These include: T57D, T65D, T65DR and the current DS86
dosimetry systems. The new dosimetry was introduced simultaneous
to the breaking of the initial cohort groups within the ongoing
RERF study population. There are many variables in considering true
exposure: not an exact system.
* Gamma vs. Neutron exposures: U235 in
Hiroshima (10% neutron), Pu239 in Nagasaki (nearly all gamma).
* Neutron RBE, Activation nuclide generation
and exposure, neutron and gamma shielding and capture, etc.
* Fallout and environmental exposure after
the initial (less than 1 microsecond) gamma and neutron flux.
APPLICATION OF DATA TAKEN FROM STUDY POPULATION
TO US POPULATION [GOF-90]
There is debate about the transfer of
information from, for example, A-Bomb survivors to a mixed US population.
In Japan there is a higher rate of stomach cancer than in the U.S.
and in the U.S. there is a higher rate of breast cancer than in
Japan. It has been argued that using the relative risk method and
A-Bomb data could therefore inflate the projected risk of stomach
cancer and underestimate the risk of breast cancer in a mixed exposure
in the U.S.
ESTIMATE OF ONGOING RADIATION INDUCED
CANCER FOR U.S. POPULATION (GOF-90; 25-15) In the U.S.: approx.
22% die of cancer = 2,200 cancer deaths / 10,000 people From GOF-90,
pg25-15 26 cancer deaths / 10,000 people per rem of full body exposure
60 year dose accumulation calculation:
THE DIAGNOSTIC X-RAY RISK TABLES FOLLOWING BASED ON:
37.30 FATAL CA/104 PERSON*RAD [GOF-85]
Diagnostic X-rays increase a patients lifetime
risk of cancer - the risk is quantifiable and has been quantified.
· There is no threshold of risk with respect to diagnostic X-rays
or any other type of ionizing radiation. · Most conservative model
of risk: supralinear at low doses; certainly no less than linear dose
- response. · Malignant transformation is related to high speed electron
tracks through cell nuclei resulting in ionization of portions of
the DNA strands and subsequent misrepair of those strands. If the
wrong portion of the molecule is damaged, malignancy can be the result.
· Radiation risk is additive with respect to total lifetime dose &
multiplicative with respect to risk of cancer induction [ (excess
risk) x (unexposed cancer rate) ] i.e. relative risk model is consistent
with data
Metaphor: blindfolded person firing
gun in random directions from 1000 yds away; target at 1000 yds
distant is unlikely to be struck over 1 minute if the gun is fired
at a 1x / min. rate. If, however, the target remains in place for
several years, or if the gun is fired at a very rapid rate, the
statistical risk becomes quite high that eventually, the target
will be struck. Thus, exposure risk is independent of rate and is
additive with respect to total exposure.
Dose to peak effect = 40 years after latency
of 10-12 years for solid cancers and for leukemia peak effect = 7-10years.
· Duration of increased relative risk of cancer appears to be lifelong
and follows the relative risk model · Cancer risk is dependent on
age at irradiation, sex and baseline organ specific cancer rates.
· Medical X-rays are twice as damaging to biologic systems as are
gamma rays produced by radionuclides · Minimum risk est. for mixed
U.S. pop. from gamma: 1 extra cancer fatality / 268 - 2878 people
irradiated w/ 1 rad. · Conservative risk est. " " U.S. pop. from X-rays:
1 extra cancer fatality / 179 - 616 people irradiated w/ 1 rad. ·
The diagnostic X-ray risk table to follow is based on:1 extra cancer
fatality / 268 people irradiated w/ 1 rad
SUMMARY:
Exercise caution with x-rays, consider the
organ dose & risk/benefits to pt. This diagnostic tool is not without
significant risk of lifetime cancer induction. As information is available,
we are obligated to obtain informed consent for any radiological procedure
(w/ the understanding that full risk table accuracy must be given
as a range of as much as 10x less risk than these tables state based
on lowest risk assumptions of BEIR V. It is better to err on the side
of conservatism & safety than to use risk assessments influenced by
financial considerations of nuclear clean-up, worker safety, plutonium
trade & nuclear technology export. Read radiation studies with care,
common pitfalls include: small sample sizes, dosimetry errors (look
for true organ doses), not controlling for sex & age at exposure,
not calculating lifetime effect (ie. limited follow-up), and failing
to analyze confounding variables (typical of environmental studies).
REFERENCES:
INTRODUCTION/PURPOSE:
NYT88 See GOF90 - New York Times pA-16,
July 14, 1988 Wald, Matthew L., "Cleanup Estimate for A-Bomb Plants
is Called Low,"
NYT89 See GOF90 - New York Times, 2/25/89
Associated Press, "Rise in Cleanup Cost Seen"
H. Phys1997 Health Physics 1997 Feb;72(2):204-21
Guenther CF, Thein C "Estimated cost of person-Sv exposure" ERRATUM
appears in H.Phys. 1997 May;72(5):804
SUMMARY RISK TABLE
ICRU-86 Int.Commission on Radiation Units
& Measurements 1986, "The Quality Factor in Radiation Protection";
ICRU report 40. Report to the ICRP and ICRU of a joint task group.
Bethesda, Md. BEIR V Health Effects of Exposure to Low Levels of
Ionizing Radiation, Committee on the Biological Effects of Ionizing
Radiations. Board on Radiation Effects Research, Commission on Life
Sciences, National Research Council; ISBN 0-309-03995-9 National
Academy Press, Washington, D.C.
1990 GOF-81 John W. Gofman, Radiation
and Human Health. 908 pages. ISBN 0-87156-275-8. Sierra Club Books,
SF
1981 GOF85 Gofman, John W. & O'Connor,
Egan X-Rays: Health Effects of Common Exams 439 pages, ISBN 0-87156-838-1,
Sierra Club Books 1985
GOF-90 John W. Gofman, Radiation-Induced
Cancer from Low-Dose Exposure: An Independent Analysis. 480 pages.
ISBN 0-932682-89-8. Committee for Nuclear Responsibility, San Francisco
1990.
US EPA94 EPA 402-R-93-076 June 1994 "Estimating
Radiogenic Cancer Risks"
UNSCEAR88 United Nations Scientific Committee
on the Effects of Atomic Radiation, 1988. Sources, Effects and Risks
of Ionizing Radiation. New York. ISBN 92-1-142143-8
ICRP91 International Commission on Radiological
Protection ICRP, Pub 60, Annals of the ICRP 21, Pergamon Press,
NY
PHYSICAL PROPERTIES
GOF-81 John W. Gofman, Radiation and Human
Health. 908 pages. ISBN 0-87156-275-8. Sierra Club Books, SF
1981 RADIATION UNITS GOF-81 John W. Gofman,
Radiation and Human Health. 908 pages. ISBN 0-87156-275-8. Sierra
Club Books, SF 1981
RADPROT81 Radiation Protection: A guide
for Scientists and Physicians 2nd edition, Jacob Shapiro, Harvard
Univ. Press; Cambridge, Mass. 1981 ISBN 0-674-74584-1
ENERGY DEPOSITION INTO TISSUES
GOF-81 John W. Gofman, Radiation and
Human Health. 908 pages. ISBN 0-87156-275-8. Sierra Club Books,
SF 1981 RPROTST83 Radiation Protection for Student Radiographers,
Mary Alice Statkiewicz and E. Russell Ritenour, C.V. Mosby, St.
Louis 1983 ISBN 0-940122-10-3 BJR89 Brenner DJ, Amols HI, Br. J.
Radiol. 1989 Oct;62(742):910-4 "Enhanced risk from low-energy screen-film
mammography X-rays. DNA DAMAGE Ward 1985 Rad.Research 103:383-392
"Mammalian Cells Are Not Killed by DNA Single-Strand Breaks Caused
by Hydroxyl Radicals from Hydrogen Peroxide" Ward 1988 Progress
in Nucleic Acid Research & Molecular Biol. V35:95-125 "DNA Damage
Produced by Ionizing Radiation in Mammalian Cells: Identities, Mechanisms
of Formation, and Repairability" Ward 1990 Int.Jrnl of Rad.Biol.
Vol57:1141-1150 "The Yield of DNA Double-Strand Breaks Produced
Intracellularly by Ionizing Radiation: A Review" Ward 1991 Rad.Research
126: 385-87 Letter "Comments to commentary by D. Billen" Ward 1995
Rad.Research 142: 362-368 "Radiation Mutagenesis: The initial DNA
Lesions Responsible" Errata 143:355 Baverstock 1991 Rad.Research
126:383-84 Letter "Comments on the Commentary by D. Billen" Brenner
& Ward 1992 Int.J.Radiation Biol, 61:737-748 "Constraints on energy
depositions and target size of multiply-damaged sites associated
with DNA double-strand breaks" (In NCRP 1998 Draft Rpt.) Goodhead,
DT 1994 H.Phys. 55:231-240 "Spatial and temporal distribution of
energy" (In NCRP 1998 Draft Rpt.) Jeggo PA Rad.Research 150 (Supppl.),
S80-S91 1998 "Identification of Genes Involved in Repair of DNA
Double-Strand Breaks in Mammalian Cells" Pfeiffer P 1998 Toxicology
Letters 96, 97:119-129, 1998 "The mutagenic potential of DNA double-strand
break repair"
DISEASES ASSOCIATED WITH INABILITY TO REPAIR
DNA LESIONS
Borek CE, et al Nature 301:156-158, 1983
"X rays may be twice as potent as X rays for malignant transformation
at low dose" Chan JYH et al Nature 325:357-359, 1987 "Altered DNA
ligase I activity in Bloom's syndrome cells" Willis AE, Lindahl
T. Nature 325:355-357, 1987 "DNA ligase I deficiency in Bloom's
syndrome" Cleaver JE Nature 218:652-656, 1968 "Defective repair
replication of DNA in xeroderma pigmentosum" Hecht F, Hecht BK Am.J.
Pediatr. Hematol.Oncol 9:185-188, 1987 "Chromosome changes connect
immunodeficiency and cancer in ataxia telangiectasia" Langlois RG,
et al Proc. Natl. Acad. Sci. 86:670-674, 1989 "Evidence for increased
in vivo mutation and somatic recombination in Bloom's syndrome"
Khan SG, et al J Investigative Dermatology 111(5):791-796, 1998
"Xeroderma Pigmentosum Group C Splice Mutation Associated with Autism
and Hypoglycinemia" Sikpi MO, et al Radiation Research 150:627-635,
1998 "Defective Modulation of Double-Strand Break Repair in Ataxia
Telangiectasia Cells by Gamma Radiation" Groisman IJ, et al Carcinogenesis
20(3):479-483, 1999 "Downregulation of DNA excision repair by the
hepatitis B virus-x protein occurs in p53-proficient and p53-deficient
cells" Becker SA, et al Journal of Virology 72(1):266-272 1998 "Hepatitis
B Virus X protein Interferes with Cellular DNA Repair" GOF-90 John
W. Gofman, Radiation-Induced Cancer from Low-Dose Exposure: An Independent
Analysis. 480 pages. ISBN 0-932682-89-8. Committee for Nuclear Responsibility,
San Francisco 1990.
GENOMIC INSTABILITY:
Morgan WF, et al Rad.Research 146:247-258
1996 "Genomic Instability Induced by Ionizing Radiation" Nowell
1976 Sci 194:23-28 (Oct'76) "The Clonal Evolution of Tumor Cell
Populations" Cheng 1993 Adv. in Cancer Res. 60:121-156 "Genomic
Instability and Tumor Progression: Mechanistic Considerations' Kadhim
1992 Nature 355:738-40 "Transmission of Chromosomal Instability
after Plutonium Alpha-Particle Irradiation" Kadhim 1994 Lancet 344:
987-88 "Alpha-Particle Induced Chromosomal Instability in Human
Bome-Marrow Cells" Kadhim 1995 Int. Journal of Radiation Biol 67:287-333
"Radiation-Induced Genomic Instability: Delayed Cytogenetic Aberrations
and Apoptosis in Primary Human Bome-Marrow Cells" Holmberg 1993
Mutation Research 286:321-330 "Clonal Chromosome Aberrations and
Genomic Instability in X-Irradiated Human T-Lymphocyte Cultures"
Marder 1993 Molecular and Cell Biol 13:6667-77 "Delayed Chromosomal
Instability Induced by DNA Damage" Mendonca 1993 Radiation Research
134:209-16 "Delayed Heritable Damage and Epigenetics in Radiation-Induced
Neoplastic Transformation of Human Hybrid Cells" Kronenberg 1994
Int.Journal of Radiation Biol 66:603-609 "Radiation-Induced Genomic
Instability" Ullrich RL & Ponnaiya B Int. J. Radiat. Biol. 74(6):747-754
"Radiation-induced instability and its relation to radiation carcinogenesis"
BEIR V Pg.138 - Health Effects of Exposure to Low Levels of Ionizing
Radiation, Committee on the Biological Effects of Ionizing Radiations.
Board on Radiation Effects Research, Commission on Life Sciences,
National Research Council; ISBN 0-309-03995-9 National Academy Press,
Washington, D.C. 1990
MONOCLONAL CANCER ORIGIN:
Evans 1979 Evans,HL Nature 277: 531-534
2/15/79 "Chromosome aberrations in nuclear dockyard workers"; Lloyd
1988 Lloyd International Journal of Radiation Biology 53 #1 p49-55,
1988 "Frequencies of chromosomal aberrations in human blood lymphocytes
by low dose of x-rays" Wainscoat&Frey 1990 Cancer Res. 50:1355-1360
"Assessment of clonality in human tumors: a review" Worsham, MJ
et al 1996 Modern Pathology 9:163-165 "Molecular genetic fingerprints:
clues to monoclonal origin of multifocal disease" Nowell 1976 Sci
194:23-28 (Oct'76) "The Clonal Evolution of Tumor Cell Populations"
Noguchi 1992 Cancer Res. 52: 6594-6597 "Clonal analysis of human
breast cancer by means of polymerase chain reaction" Fialkow 1976
Biochem. Biophys. Acta 458:283-321 "Clonal origin of human tumors"
Fialkow 1984 "Clonal evolution of human myeloid leukemias," p215-226
in Genes and Cancer: UCLA Symposia on Molecular and Cellular Biology,
Bishop and Rowley Eds., NY Arnold et al 1983 NEJM 309:1593-1599
"Immunoglobulin gene rearrangements as unique clonal markers in
human lymphoid neoplasms" Cleary et al 1988 J. Exp. Med. 167:582-597
"Single cell origin of bigenotypic and bigenotypic B cell proliferations
in human follicular lymphomas" Levy et all 1977 J. Exp. Med 145:1014-1028
"The monoclonality of human B. cell lymphomas" Minden et al 1985
Proc. Natl. Acad. Sci. 82:1224 "Somatic rearrangement of T-cell
antigen receptor gene in human T-cell malignancies"
RELATIVE RISK RESPONSE
Gof-Tamplin 1969 Gof-Tamplin 1970 GOF-81
John W. Gofman, Radiation and Human Health. 908 pages. ISBN 0-87156-275-8.
Sierra Club Books, SF 1981 GOF-90 John W. Gofman, Radiation-Induced
Cancer from Low-Dose Exposure: An Independent Analysis. 480 pages.
ISBN 0-932682-89-8. Committee for Nuclear Responsibility, San Francisco
1990. NCRP98 National Council on Radiation Protection and Measurements
(NCRP) Draft Report SC 1-6. Oct. 1998 "Evaluation of the Linear
Nonthreshold Dose-Response Model" , Bethesda, Maryland GOF-81 John
W. Gofman, Radiation and Human Health. 908 pages. ISBN 0-87156-275-8.
Sierra Club Books, SF 1981
SHAPE OF RELATIVE RESPONSE CURVE
Gof-Tamplin 1969 Gof-Tamplin 1970 NCRP98
Oct'98 NCRP Draft Rpt SC 1-6 "Evaluation of the Linear Nonthreshold
Dose-Response Model" BEIR V Health Effects of Exposure to Low Levels
of Ionizing Radiation, Committee on the Biological Effects of Ionizing
Radiations. Board on Radiation Effects Research, Commission on Life
Sciences, National Research Council; ISBN 0-309-03995-9 National
Academy Press, Washington, D.C. 1990 GOF-81 John W. Gofman, Radiation
and Human Health. 908 pages. ISBN 0-87156-275-8. Sierra Club Books,
SF 1981 GOF-90 John W. Gofman, Radiation-Induced Cancer from Low-Dose
Exposure: An Independent Analysis. 480 pages. ISBN 0-932682-89-8.
Committee for Nuclear Responsibility, San Francisco 1990. RERF91
RERF Update 3(4):14, 1991 [see www.rerf.or.jp/] RERF92 Voeth,M.
Preston, D.L, RERF Update 4(3):5-6, 1992 "Extrapolating Life Span
Study cancer risk estimates to low dose exposure"
NO THRESHOLD
UNSCEAR93 United Nations Scientific Committee
on the Effects of Atomic Radiation. Sources and Effects of Ionizing
Radiation: UNSCEAR 1993 Report to the General Assembly, with Scientific
Annexes. 922 pages. ISBN 92-1-142200-0 GOF-90 John W. Gofman, Radiation-Induced
Cancer from Low-Dose Exposure: An Independent Analysis. 480 pages.
ISBN 0-932682-89-8. Committee for Nuclear Responsibility, San Francisco
1990. NCRP98 Oct'98 NCRP Draft Rpt SC 1-6 "Evaluation of the Linear
Nonthreshold Dose-Response Model"
DURATION OF EFFECT
GOF-81 John W. Gofman, Radiation and
Human Health. 908 pages. ISBN 0-87156-275-8. Sierra Club Books,
SF 1981 GOF-90 John W. Gofman, Radiation-Induced Cancer from Low-Dose
Exposure: An Independent Analysis. 480 pages. ISBN 0-932682-89-8.
Committee for Nuclear Responsibility, San Francisco 1990. BEIR V
Pg.52 Health Effects of Exposure to Low Levels of Ionizing Radiation,
Committee on the Biological Effects of Ionizing Radiations. Board
on Radiation Effects Research, Commission on Life Sciences, National
Research Council; ISBN 0-309-03995-9 National Academy Press, Washington,
D.C. 1990
AGE & SEX EFFECT ON RADIATION SENSITIVITY
GOF-81 John W. Gofman, Radiation and
Human Health. 908 pages. ISBN 0-87156-275-8. Sierra Club Books,
SF 1981 Hemplemann et al 1975 Journal of Nat.Can.Institute 55:519-30
"Neoplasms in persons treated with X-rays in Infancy: fourth survey
in 20years Shore et al 1977 Journal of the National Cancer Institute
59:813-22 "Breast neoplasms in women treated with X-rays for acute
postpartum mastitis" Boice, Monson 1977 Journal of the National
Cancer Inst. 59:823-832 1977 "Breast cancer in women after repeated
fluoroscopic examinations of the chest" Shore et al 1976 Archives
of Environmental Health 31:21-28 "Follow-up study of patients treated
by X-ray epilation for tinea capitis. Re-survey of post-treatment
illness and mortality experiences" RERF91a RERF 3(2):10, 1991
ORGAN SPECIFIC CANCER RATES FOLLOW RELATIVE
RISK MODEL
RERF90a Mabuchi,K. RERF 2(2) 5-6, 1990
"LSS Cancer Incidence Tracked by Tumor Registries" RERF94 Mabuchi,
K. Preston, D. RERF 6(1):3-4, 1994 "Cancer Incidence in Atomic-bomb
Survivors" GOF-81 John W. Gofman, Radiation and Human Health. 908
pages. ISBN 0-87156-275-8. Sierra Club Books, SF 1981 GOF-90 John
W. Gofman, Radiation-Induced Cancer from Low-Dose Exposure: An Independent
Analysis. 480 pages. ISBN 0-932682-89-8. Committee for Nuclear Responsibility,
San Francisco 1990. Land CE, Sinclair WK 1991 Annals of the ICRP
2#1:1991 In Risks Associated with Ionizing Radiations: "The relative
contributions of different organ sites to the total cancer mortality
associated with low-dose radiation exposure"
ADAPTIVE RESPONSE
UNSCEAR 1977 p378 - United Nations Scientific
Committee on the Effects of Atomic Radiation 1977. Sources and effects
of ionizing radiation. Report to the General Assembly, with annexes.
United Nations, New York. NCRP98 BEIR V Health Effects of Exposure
to Low Levels of Ionizing Radiation, Committee on the Biological
Effects of Ionizing Radiations. Board on Radiation Effects Research,
Commission on Life Sciences, National Research Council; ISBN 0-309-03995-9
National Academy Press, Washington, D.C. 1990 RERF92 RERF Update
4(3):5-6, 1992 Voeth, M. Preston, D.L. "Extrapolating Life Span
Study cancer risk estimates to low dose exposure" Little MP & Boice
JD Rad.Research 151:218-224, 1999 "Comparison of Breast Cancer Incidence
in the Massachusetts Tuberculosis Fluoroscopy Cohort and in the
Japanese Atomic Bomb Survivors" Brenner DJ Rad.Research 151:225-229,
1999 "Does Fractionation Decrease the Risk of Breast Cancer Induced
by Low-LET Radiation?"
DATABASE - PERFECT EXAMPLE
GOF-81 John W. Gofman, Radiation and
Human Health. 908 pages. ISBN 0-87156-275-8. Sierra Club Books,
SF 1981 GOF-90 John W. Gofman, Radiation-Induced Cancer from Low-Dose
Exposure: An Independent Analysis. 480 pages. ISBN 0-932682-89-8.
Committee for Nuclear Responsibility, San Francisco 1990.
DATABASE - HUMAN
GOF-90 John W. Gofman, Radiation-Induced
Cancer from Low-Dose Exposure: An Independent Analysis. 480 pages.
ISBN 0-932682-89-8. Committee for Nuclear Responsibility, San Francisco
1990. MacMahon, B. J. of Nat.Cancer Inst. 28:1173-1191 1962 "Prenatal
X-Ray Exposure and Childhood Cancer" Harvey E.B., et al NEJM 312#9:541-545
2/28/1985 "Prenatal X-Ray Exposure and Childhood Cancer in Twins"
Hoffman, D.A. et al J. of Nat.Cancer Inst 81#17:1307-1312 9/6/1989
"Breast Cancer in Women with Scoliosis Exposed to Multiple Diagnostic
X-Rays" Miller, A.B. et al NEJM 321#19:1285-1289 "Mortality from
Breast Cancer after Irradiation during Fluoroscopic Examinations"
Baverstock, KF, Vennart, J. H.Phys 44, Suppl.#1:575-577, 1983 "A
note on Radium Body Content and Breast Cancers in UK Radium Luminisers"
Baverstock, K,Papworth D. Br.J.Radiol., Suppl. BIR Rpt 21:71-76,
1987 "The U.K. Radium Luminizer Study" Daverst, et al Lancet 1:430-433,
2/21/81 "Risk of Radiation at Low Dose Rates" GOF-81 John W. Gofman,
Radiation and Human Health. 908 pages. ISBN 0-87156-275-8. Sierra
Club Books, SF 1981 Beebe, Kato & Land1978 Rad.Research 75:138-201
"Studies of the mortality of A-bomb survivors: 6 Mortality & radiation
dose, 1950-1974 Nishiyama et al 1973 Cancer 32:1301-09 "The incidence
of malignant lymphoma and multiple myeloma in Hiroshima and Nagasaki
atomic bomb survivors 1945-1965 UNSCEAR 1977 p378 United Nations
Scientific Committee on the Effects of Atomic Radiation 1977. Sources
and effects of ionizing radiation. Report to the General Assembly,
with annexes. United Nations, New York. Takeichi et al 1976 Cancer
38:2462-68 1976 "Salivary gland tumors in atomic bomb survivors,
Hiroshima, Japan" Boice et al 1979 Radiology 131:589-597 "Risk of
breast cancer following low-dose radiation exposure" BEIR III 1979
The effects on populations of exposure to low levels of ionizing
radiation DRAFT RPT. Division of Medical Sciences. Assembly of Life
Sciences, National Research Council, National Academy of Sciences.
Hemplemann et al 1975 Journal of Nat.Can.Institute 55:519-30 "Neoplasms
in persons treated with X-rays in Infancy: fourth survey in 20years
Janower & Miettenen'71 Journal of the American Medical Association
215:753-56 "Neoplasms after childhood irradiation of the thymus
gland" Conti et al 1960 Radiology 74:386-391 "Present health of
children given X-ray treatment to the anterior mediastinum in infancy
Shore et al 1977 Journal of the National Cancer Institute 59:813-22
"Breast neoplasms in women treated with X-rays for acute postpartum
mastitis" Mettler, et al 1969 Journal of the Nat.Cancer Institute
43:803-11 "Breast neoplasms in women treated with X-rays for acute
post-partum mastitis; a pilot study" Boice, Monson 1977 Journal
of the National Cancer Inst. 59:823-832 1977 "Breast cancer in women
after repeated fluoroscopic examinations of the chest" Boice, J.D.
Rad.Research 73:373-390, 1978 "Estimation of Breast Doses and Breast
Cancer Risk Associated with Repeat Fluoroscopic Chest Examination"
Delarue et al Canadian Med. Association Journal 112:1405-13 "Multiple
fluoroscopy of the chest: carcinogenicity for the female breast
and implications for breast cancer screening programs" Myrden in
BEIR III p679: Canadian Med. Assoc.Jrnl 100:1032-1034, 1969 "Breast
Cancers Following Multiple Fluoroscopies during Artificial Pneumothorax
Treatment of Pulmonary Tuberculosis" Shore et al 1976 Archives of
Environmental Health 31:21-28 "Follow-up study of patients treated
by X-ray epilation for tinea capitis. Re-survey of post-treatment
illness and mortality experiences" Moden et al 1977 Radiology 123:741-44
"Thyroid cancer following scalp irradiation" Modan, B et al 1989
Lancet 1:629-631, 3/25/89 "Increased Risk of Breast Cancer after
Low-Dose Irradiation" Brinkley & Haybittle '69 British Journal of
Radiology 42:519-21 "The late effects of artificial menopause of
X-radiation" Court,Brown,& Doll '65 British Med. Journal 2:1327-32
"Mortality from cancer and other causes after radiotherapy for ankylosing
spondylitis" Baral et a l 1977 Cancer 40:2905-10 "Breast cancer
following irradiation of the breast" BEIR V Health Effects of Exposure
to Low Levels of Ionizing Radiation, Committee on the Biological
Effects of Ionizing Radiations. Board on Radiation Effects Research,
Commission on Life Sciences, National Research Council; ISBN 0-309-03995-9
National Academy Press, Washington, D.C. 1990 RERF Pierce DA, Vaeth
M "Cancer risk estimation from the A-bomb survivors: Extrapolation
to low doses, use of relative risk models, and other uncertainties";
RERF CR 2-89 (1989); "The shape of the cancer mortality dose-response
curve for atomic survivors"; RERF TR 7-89; and Radiat Res 121:1
20-41 (1990) Shimizu Y, et al Life Span Study Report 11. Part 2:
"Cancer mortality in the years 1950-1985 based on the recently revised
doses (DS86)"; RERF TR 5-88 and Radiat Res 126:36-42 (1991) Darby,
SC, et al 1987 Br. J. Cancer 55:179-190, 1987 "Long-term mortality
after a single treatment course with X-rays in patients treated
for ankylosing spondylitis" Hrubec, S, et al 1989 Cancer Res. 49:229-234,
1989 "Breast cancer after multiple chest fluoroscopies: Second follow-up
of Massachusetts women with tuberculosis" Shore, RE, et al 1985
J. Natl. Cancer Inst. 74:1177-1184, 1985 "Thyroid tumors following
thymus irradiation" Shore, RE, et al 1986 J. Natl. Cancer Inst.
77:689-696, 1986 "Breast cancer among women given x-ray therapy
for acute postpartum mastitis" Ron E 1998 Rad.Research 150 (Suppl.),
S30-S41, 1998 "Ionizing Radiation and Cancer Risk: Evidence from
Epidemiology"
DATABASE - IN VITRO [VERY SMALL SAMPLE]
Brown, J.M. 1976 Health Physics 31:231-245
"Linearity versus non-linearity of dose-response for radiation carcinogenesis.
Brown J.M. 1977 Rad.Research 71:34-50 "The shape of the dose-response
curve for radiation carcinogenesis: extrapolation to low doses"
Evans et al 1979 Nature 277:531-534 "Radiation-induced chromosome
aberrations in nuclear-dockyard workers" Grosovsky AJ, Little JB
"Evidence for linear response for the induction of mutations in
human cells by x-ray exposures below 10 rads. Proc Natl Acad Sci
USA 82: 2092-2095 (1986)
DATABASE - ANIMAL [VOLUMINOUS] see BEIR-V
pp125-134, 153-160, 334-351
CRITICISM OF BEIR V AND RERF
GOF-90 John W. Gofman, Radiation-Induced
Cancer from Low-Dose Exposure: An Independent Analysis. 480 pages.
ISBN 0-932682-89-8. Committee for Nuclear Responsibility, San Francisco
1990. GOF-96 John W. Gofman, Preventing Breast Cancer: The Story
of A Major, Proven, Preventable Cause of This Disease" 2nd ed. 424
pages. ISBN 0-932682-96-0. Committee for Nuclear Responsibility,
San Francisco 1996. GOF85 Gofman, John W. & O'Connor, Egan X-Rays:
Health Effects of Common Exams 439 pages, ISBN 0-87156-838-1, Sierra
Club Books 1985 Roesch, William C. ed U.S.-JAPAN JOINT REASSESSMENT
OF ATOMIC BOMB RADIATION DOSIMETRY IN HIROSHIMA AND NAGASAKI: FINAL
REPORT, VOL. 1., DS86 DOSIMETRY SYSTEM 1986, Hiroshima: RERF. DATA
ANALYSIS TECHNIQUES GOF-90 John W. Gofman, Radiation-Induced Cancer
from Low-Dose Exposure: An Independent Analysis. 480 pages. ISBN
0-932682-89-8. Committee for Nuclear Responsibility, San Francisco
1990.
DATA TECHNIQUE: APPLICATION TO US POPULATION
GOF-90 John W. Gofman, Radiation-Induced
Cancer from Low-Dose Exposure: An Independent Analysis. 480 pages.
ISBN 0-932682-89-8. Committee for Nuclear Responsibility, San Francisco
1990.
CANCER RATES FOR US POPULATION - ORGAN SPECIFIC
PER RADIATION DOSE
GOF-90 John W. Gofman, Radiation-Induced
Cancer from Low-Dose Exposure: An Independent Analysis. 480 pages.
ISBN 0-932682-89-8. Committee for Nuclear Responsibility, San Francisco
1990. GOF-85 Gofman, John W. & O'Connor, Egan X-Rays: Health Effects
of Common Exams 439 pages, ISBN 0-87156-838-1, Sierra Club Books
1985
RISK TABLES - COMPARING MAJOR AGENCIES
EPA 1994 EPA402-R-93-076 June 1994 "Estimating
Radiogenic Cancer Risks" GOF-81 pg314: John W. Gofman, Radiation
and Human Health. 908 pages. ISBN 0-87156-275-8. Sierra Club Books,
SF 1981
ROUTINE DIAGNOSTIC X-RAY TABLES
GOF85 Gofman, John W. & O'Connor, Egan
X-Rays: Health Effects of Common Exams 439 pages, ISBN 0-87156-838-1,
Sierra Club Books 1985