|
Items in cart [0] |
Questions? Call 888-624-8373 |
| Copyright © 2009. National Academy of Sciences. All rights reserved. Terms of Use and Privacy Statement |
Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 504
APPENDIX Vi}
The Combined Effects of Radon Daughters
and Cigarette Smoking
Part 1 of this appendix reviews the epidemiological literature on the
combined health effects of smoking and radiation. The studies reviewed
by the committee are summarized in Table VII-1. Part 2 presents the
committee's analyses of lung-cancer occurrence in persons exposed to both
carcinogens. Part 3 summarizes the committee's views, including the
possible effects of smoking on the validity of dose estimates and the need
for further studies of the combined effects of radon daughters and smoking.
PART 1. Epidemiological Studies of
Smoking and Radiation
STUDIES AMONG SWEDISH METAL MINERS
Studies of iron-ore miners in Northern Sweden reveal an excess of lung
cancer that is related primarily to underground employment and exposure
to radon.~7~28 In order to clarify the role of raxlon exposure combined
with tobacco use on the occurrence of lung cancer, D amber and Larssoni°
carried out a case-control study in a three-county area of Northern Sweden,
in which cases were ascertained in the years 1972-1977. As all iron mines
were found within only two municipalities, succeeding studies were focused
on the mining areas Kiruna and Gallivaxe and were extended to encompass
the years 1972-1982.~, Therefore, only the latest report is considered here.
The case group consisted of 69 lung-cancer cases who were reported
to the Swedish cancer registry after 1972 and who were deceased before
504
OCR for page 505
RADON DAUGHTERS AND CIGARETTE SMOKING
505
July 1982. For each case, one deceased control was drawn from the
National Registry for Cause of Death, matched by sex, year of death, age,
and municipality; suicides and lung carcinomas were not included in the
control group. A second living control for 60 cases aged 80 and under was
selected from the Swedish National Population Registry and matched by
sex, year of birth, and municipality.
As recognized by the authors, smoking-related risks that are based
on deceased controls may be underestimated, since tobacco use was likely
to have been greater by the deceased than by the general population.
However, use of controls required to be alive until 1982 may overestimate
relative risks since their smoking rates may be may have been less than
those of the general population at risk. Nevertheless, the results presented
by Damber and Larrsont° were generally comparable, regardless of control
group.
Interviews were conducted with the index subject or the next of kin
to obtain information on smoking practices and work history. Members of
the study group who worked underground in an iron mine were considered
exposed to radon. Since no accurate measurements of direct radon exposure
were available, the surrogate variable, years underground, was used for
analysis.
Smoking data consisted of the year tobacco use started the number of
cigarettes smoked per day, and the year of cessation of smoking. Smokers
were individuals who consumed one cigarette daily for at least 1 yr. For
cigar and pipe smokers, 1 g of tobacco was equated to one cigarette.
Results were tabulated by three categories of lifetime tobacco use:
nonsmoker, low (150,000 cigarettes)
consumption. For cases and deceased controls, relative risks rose from
the baseline 1.0 for nonsmokers to 2.4 to 8.4 for aboveground workers
and from 5.4 to 21.7 to 69.7 among underground miners. Similar results
were reported for cases and the combined control group of all living and
deceased subjects. Although based on small numbers (23 cases had no
or low tobacco consumption, of which only 3 had no underground-mining
experience), the results suggest that radon exposure and smoking combine
multiplicatively rather than additively on a relative risk scale.
As outlined in Appendix IV, Radford and Renard27 reported a his-
torical cohort study of 1,415 miners from the Malmberget and Koskoskulle
areas of Sweden. Data on current smoking habits were reported from
388 questionnaires administered in 1972-1973 to active miners and surface
workers (35%0 of the contemporary work force) and from 168 pensioners.
Pipe smoking was considered equivalent to cigarette smoking. Although
pipe smoking has been related to lung-cancer risk, the affect of this as-
sumption is difficult to assess since information on the percentage of pipe
smokers and their inhalation patterns was not provided. The authors state
OCR for page 506
506
CQ
·_
Ct
-
5-
o
x
o
.~
._
-
C.
-
so
C.
._
V
Can
o
U.
·O
V'
C)
a'
V]
to
5-
C~
V,
._
._
PA
EM
Cal
U.
Cal
Hi:
.=
U.
a
O u,
~ ~ ~ ~ ~ e . ~ 3 3 ~ ~ ~ ~ ~ ~ ~ E
V] ~ V,
0~- ~ 3 it
_;; O ~ ~ _ ~ ~ ~ At,
~ ~ 0 ~ ~ ~
~ ~ . ~ ~= 3,: a =0 ~ , ~
~ =O
3 3
(3 ~ ~
I_ ~ ~ _
·_ V' Ct ~ o
OCR for page 507
507
. ~ . ~ U) o
·~ O ~ ~ ~ o ~ 5
2 ~ ~ i, ~— ~ r = — -
A
of
rat
O
- 0
O
_
c,
td O
.= _
~ O
O
O
oo ret
. . . . . . l
00 ~ ~ ~ ~ O
us ct
o
_ ~ O.
~ ~ ~ us ~ ~ ~ _
~ I, ~
c,
_ ED oo ~ ~ Ce
_ _ ~ l— ~ 00 ·= ~
~ ~ O
cr ~ ~ ~ +
_ _ us ~ O
~ _
O ~ O O O ,~
_
_
~ O _ 00 ~ 00
. . . . . .
_ ~ ~ ~ ~
_
oO oo 0 r~
O
s~
: -
00 ~ ~ ~ O ~ ~
. . . . . . cd
r~ u~ u~ ~ ~ ~ S:~
_ _ ~ ~ _
c'
a~
— O _ ~ ~ O t~
O ~ ~ ~ ~=,
rn c~
04
._
O
_
O
C~ 0. ~ ~ oO ~
— O ~ oo t— t—
_ ~ ~
o
~4
s"
s"
~ O
_ ~ ~ U-) 1
U) _ ~ ~ =,
1 1 1 1 1 0
O O O O O
oo
_ ~ ~
~ ~ O
. . .
oO
_ ~
_ oO
. . .
O
r~
. .
_ r~ ~
2 2 2- ,,
2 s 2 - ~ 2 ~ ~ '
x
.m
O {~'
~ ~ ~ ~ ~
O O >. O ~ c,
OCR for page 508
508
Cal
it:
C)
U)
A>
to
woo
2Co
o
4-
C.
~ -O
a Id x
-
A:
U.
~ ._
._ 53
~ ~ K
4
4V·S ~
~ Cal 04
·- ~ o
-t ° e. ~
C,
o ~ ~ ID
-
U.
C.
~4
.o
UP ~ ~ O _
0 - 0
O t- Ir) O
l
10
_ _
_ O.
U) _ ~
O. ~ O.
V _ _ m0
O
._ no
a ~ O ~ ~ +
~ ~ V O ~ (0~
U)
.a
.=
~ -
~ ~ -
- cd ~
~ ~ £
._, 4 ~
~5 °
X ~
._
B ·= ~
U)
i: ~ U
:- ~ ~
U'
o ~
.O &
£~
= C~ ~ o
C) o .a o
U. ~
o tlo-_ C.,
~a £ ~ s:
~ et e~ ._
V'
U.
o~
~,
.=
c: ~
Ct
.=
.O
o.~ ~
s
° o 3
5- U)
o
B ~ ~
o ~ {O.
-
Ct
:^ B
S ~r
£ ==
·— C,~
c: e~ Ct
V' ~
° U) ~
o ~ ~
·~ -
,~) td —
Cd C.}
._ (.
U. ~ _ o
~ ~ £.~°
r v~ <;S
d O 4 ~
t~ £ m._
w
W
- , ~ ~ ~
_ C.
.=
~'
z
~o
o ~o ~ ·U,
_ _ o
V Al
.~
s"
C)
-
~ O. ~ ~ ~ .=
W —' — ~,o ~ ~
~ W U) W 0,0 0
3 ~ ~ ~ C
"o ~ £ =- "°
2
o o
W ~ ~ ~
~d ~ ~ ~ — O
e~
-
w
B
-
e~
W
o
w
.>
. -
s:
~C:
w
.>
. - :^
=
~ ::
_
~ W
~W ~
:- ~
._ ~
CI: ~
·— U,
O4—
._ ~
~ o
~ £
s:
o ~ 3
-~- W
cr ~
z
U,
W
~'
~ ~ .=
s"
-
W
V,
o
~i
o
._
._
et
O _
~ W
o .= 3
W ~ ~ W
= E -- ~W
~ ° 3 ~ ~
_ ~ ~ t;~ o
:, ~ ~ ~ ~
-
Ct
-
-
. . .
~ ~ ~.
o mg
V ° A
OCR for page 509
son
~ -
.~ :^
~ -
to
:-
. - ~
its ~
· - A,
. - ~
- o
c ¢¢ 3
m
o
A
-
-
o
-
-
o
~,
o s"
.~ o
e~ X
P~
~ ~4
oo o s:
o ~ o
_ _ Z
_,
U. _
o ~ ~
C} .~ ~,
~ Sed C~ ·—
~ !E ~ E
C.
v
_
_
_
~, _
.^ o
4D ·—
<: ~
— 4
e~
_,
U~ ~ oo
. . —
~ _ r~
~ ~ . ~ ~ ~
~ ~ ~o 0 A ~ _ I
~ o ~
~ ~ ~ ~ _ ~ ~ ~ ~
C~.) _ £~=
_ _ ~ V o _ o U~,
o ~ o o ~ mo
V ° A V ° A
CQ
~D
o
o
o
e.
o
c~
c~
.O
. - c)
O4
~ x
,
~.c#, c-c
~co ~ ~ ~
.~ o 5
D ~ O C,
C) ~
C C C X
._
~ - m v,
OCR for page 510
510
HEALTH RISKS OF RADON AND OTHER ALPHA-EAiITTERS
that approxanately half the workers who were still living at the time of
the study took part in the survey of smoking habits. Smoking histories for
lung cancer patients were obtained from next of kin or, in a few instances,
from the subject. Evaluation of the quality of tobacco consumption data is
not possible, since no attempt was made to compare subjects from whom
smoking data were obtained to those for whom data were unavailable.
The smoking rate among miners is probably underestimated, since surveys
covered only living workers.
The precise method of analysis of smoking is not completely clear in
the published report. Among miners, smokers were defined as those who
had stopped smoking within 10 yr of the interview or who were currently
smoking, while nonsmokers were defined as subjects who stopped smoking
10 yr or more years to the interview or who had never smoked. The authors
assumed that risk of lung cancer for smokers relative to that for nonsmokers
is constant over age. The smoking status of miners was then compared
with a national smoking survey of 25,000 men carried out in 1963.3° It was
determined that the miners had a higher proportion of smokers. Although
apparently no adjustment was made for the different time periods of the
two surveys, the mortality experience of the national surveys was applied
to the miners and a relative risk of 7.4 for smokers versus nonsmokers was
obtained. The method for deriving the relative risk of 7.4 was not explicitly
described. The subsequent relative risks for miners to nonminers were 2.9
for smokers based on 32 lung-cancer cases and 10.0 for nonsmokers based
on 18 cases. The authors concluded that mining- and smoking-related risks
combine additively. This conclusion seems to go beyond the evidence as
presented. Radford and Renard's27 results, however, do tend to suggest
that risks for the two exposures are submultiplicative.
Within the parish of Hammar, Sweden (population, 4,000), Axelson
and Sundell3 compared smoking and mining (zinc and lead) experiences in
29 lung-cancer cases deceased between 1956-1976 with 174 referents who
died of causes other than lung cancer and who were matched to cases by
time of death. A subject was exposed if he appeared on employee files of
the mining company. For workers with mining experience (21 cases and 19
controls), foremen who were contemporaries of the subjects were contacted
and queried about the smoking status of the subjects. Smoking status was
not determined for nonminers.
Among miners, smoking appeared to be protective for lung cancer,
although the 90%0 confidence interval was large (relative risk, 0.49; 90%0
confidence interval, 0.1-2.2~. The authors explained this finding by sug-
gesting that smokers have a lower radiation-induced risk because of a
thickened mucus layer in critical bronchial segments.
Axelson and Sundell3 did not evaluate the effects of smoking among
nonminers or of mining exposure by smoking category. Because of this
OCR for page 511
RADON DAUGHTERS AND CIGARETTE SMOKING
S11
lack of information on smoking in nonmembers and on duration of radon
exposure in miners, the study could not address the mode of interaction
between radon and smoke exposures. Nevertheless, as noted in Table VII-1,
the protective effect of smoking does suggest that an interaction could be
additive or subadditive. However, potentially biased exposure assessment
procedures (for example, inadequate company files and recall bias by
the foremen), inappropriate control selection (inclusion of referents with
tobacco-related causes of death), or simply the possibility that nonsmokers
spent more time underground than smokers are alternative explanations.
STUDIES AMONG COLORADO PLATEAU MINERS
Several published reports based on the U.S. Public Health Service
cohort of uranium miners of the Colorado Plateau have evaluated in detail
the roles of radiation and cigarette smoking in the production of lung
cancerS.~.22.24,32,3e
The earliest report, by Archer et al.,, included 39 cases of lung cancer
that arose in a well-defined, physically examined special study group during
a 4-yr observation period (1964-1967~. Compared to lung-cancer rates
among white male residents of mountain states, 1.1 and 4.4/10,000 person-
yr for nonsmokers and smokers, respectively, the rates among uranium
miners were 7.1 and 42.2/10,000, respectively. These comparisons, which
show a 4-fold population-based excess for smoking and a 5.~fold miner
excess, suggest a multiplicative interaction of these agents.
Another analysis by Archer et al., reported in the same paper, focused
on a larger sample of 207 cases, whose ascertainment of health status and
population were less clearly defined but which included the 39 special study
group cases. This second analysis relied solely on comparisons of age at
lung-cancer diagnosis between groups of smoking and nonsmoking miners.
Mine-related variables, such as age at start of mining, cumulative working-
level months (WLM), and years of other hard-rock mining, were controlled
through matching. The induction-latent period was shorter for smokers
than for nonsmokers. The authors argue that the agents act synergistically.
This analysis is questionable, however, regarding the form of the model,
since in a survival model introduction of a second disease-related exposure,
that is, radon, increases age-specific hazard rates and thus increases the
probability of a tumor appearing earlier.
Lundin et al.22 evaluated 62 lung-cancer cases that developed in the
cohort of 3,366 white uranium miners followed from first medical exam-
ination through 1968. Smoking data came from periodic surveys carried
out prior to 1970. Lundin et al. used tobacco consumption information
from the last examination. Analysis was based on a log-normal model for
estimating a yearly effective radiation dose, which weighted exposure in
OCR for page 512
512
HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTI3RS
each previous year, in order to account for disease latency. Although no
formal statistical testing of hypotheses was carried out, the results suggest
that the relative-risk model for WLM exposure, In comparison with the
absolute-risk model, is more appropriate. The authors then analyzed the
effect of smoking under their assumed effective-dose model and claimed a
submultiplicative effect for smoking. The results suggest there is a greater
amount of radiation-induced lung-cancer risk among smokers, with slight
differences between heavy and light smokers, than in nonsmokers. It is
difficult to evaluate conclusions from this analysis because of the lack of
formal hypothesis testing.
A detailed study of the Colorado Plateau uranium miners in which
194 lung-cancer cases were used was carried out by Whittemore and
McMillan.38 A nested or synthetic case-control approach was used,
whereby each lung-cancer case was matched with four controls born within
8 months of the case and alive at the time the case died. Exposure histories
for controls were adjusted to reflect values up to the time the case died
(minus any lag time). With this type of analysis, relative hazard (or
relative risk) is modeled in either a multiplicative or additive way. No
direct information on disease rates are obtained, and hence, evaluation of
absolute excess risk is not possible. Data were classified by four categories
of cigarette pack-yeas (average cigarette packs smoked per day times
duration, in years, of use), accumulated from the start of exposure to a
predefined cutoff date, and six categories of WLM. A single 23-parameter
relative-risk model was fit to the two-way classification. All subsequent
models were then compared for goodness of fit to this saturated model.
Several models for the relative risk with combined cigarette and WLM
exposure were fit. Multiplicative and additive excess-risk models were fit,
as well as other richer variants, for example, mixture models of additive
and multiplicative terms for smoking and linear and quadratic terms for
radiation; exponential models were also fit. VVhittemore and McMillan38
found substantial support for the multiplicative model, finding that it fit
nearly as well as the saturated one. The authors rejected the additive
model, which agrees with a preliminary analysis reported by Hornung
and Samuels.~5 Further analyses found little improvement when smoking
rate was added to the model, although this improvement might have been
expected since pack-years incorporate cigarettes smoked per day and the
subjects were matched by age. They also reported that the smoking effect
did not interact with age.
The joint eRect of smoking and radon-daughter exposure in this cohort
was also addressed in a National Institute for Occupational Safety and
Health (NIOSH) Report to the Mine Safety and Health Administration.24
Using the Colorado Plateau miner cohort with follow-up through 1982, a
synergistic effect between these two factors was reported, that is, combined
OCR for page 513
RADON DAUGHTERS AND CIGARETTE SMOKING
513
effects exceeding the sum of the separate effects (as would be predicted by
an additive model). However, the data also suggested that the combined
effect was less than multiplicative. It is generally difficult to compare these
conclusions with other analyses of these data, since the authors relied on
a power function relative risk model. Whittemore and McMillan38 found
that linear-relative-risk models for both smoking and radon exposure,
individually, were preferrable to power-function relative-risk models.
An analysis of data from another group of Colorado Plateau workers
has recently been reported by Saccomanno et al.32 The cohort included
9,817 miners, underground and open pit, and millers who worked between
1960 and 1980 and who agreed to participate in the study.3~32 Sputum
samples were collected periodically, although irregularly, from 1957. Infor-
mation on the number of workers lost to follow-up and on the completeness
of sputum assessment was not reported. Although not explicitly stated,
exposure measurements for radon and cigarette use were likely determined
from periodic cohort surveys, as described previously for the other Col-
orado miner group.
Analyses were based on a selected case-control subsample from cohort
members who had at least one sputum specimen taken between 1960-1980
and who had a current exposure history. Cases In = 489) were defined as
men who had at least one sputum cytology specimen classified as moderate
or worse atypical squamous cell metaplasia. Controls (n = 992) were a 11%
random sample of the noncase members of the cohort. Variables of interest
were age, cumulative WLM, and pack-yea". Because of case definition,
this is a study of the determinants of moderate cell atypia or worse, and
not of lung cancer.
The results suggested a multiplicative association for the combined
effects of cigarette use and radon exposure, although formal testing pro-
cedures were not described. Based on unmatched analyses, increased
age-adjusted relative risks with duration of underground uranium mining
were similar within categories of pack-years, as were risks with cigarette
consumption for categories of underground duration. The former increases
from 1.0 for no underground experience to approximately 10.0 for more
than 10 yr of underground experience, while the latter increases from 1.0
to approximately 3.0 for more than 20 pack-years of cigarette use. The
authors also present results for logistic model fitting. Their interpretations
are not clear, and may be statistically inappropriate.
This study is also subject to several potential biasing factors. Controls
were substantially younger than cases (41.8 versus 58.2 yr, respectively)
and were more likely to have been lost to follow-up (39% versus 23% re-
spectively) or to have missing WLM data (33% versus 25%, respectively).
Although one analysis was matched on age (~2 yr), the primary analy-
sis was unmatched and relied on age adjustment, with either crude age
OCR for page 514
514
HEALI'H RISKS OF RADON AND OTHER ALPHA-EMITTERS
categories or a single age parameter in a logistic model. The adequacy of
this adjustment is hand to assess. Bias Is also possible from the method of
control selection; controls were selected from all noncase members of the
cohort, regardless of length of follow-up, instead of from cohort members at
risk at the time of case ascertainment.2t Controls were therefore likely to
be healthier and to have received less exposure to radon and tobacco. Case
selection bias, that is, more intense disease evaluation of higher-exposure
workers, could have occurred, since workers who were more highly exposed
to radon or cigarettes may have been more health conscious and therefore
more likely to submit sputum specimens and ultimately categorized as a
case. The authors did not give the mean number of specimens evaluated
prior to ascertainment for cases or at equivalent follow-up for controls.
Sputum specimens were obtained during follow-up and were used to de-
fine cases. However, men who were hospitalized or died with suspected
lung cancer were apparently also classified as cases, although their atypia
status should have been based on evaluated cytology records. Again, this
deviation from the case definition criteria may have biased results of this
study.
Using data from the 1982 follow-up of the Colorado Plateau cohort
initiated by the U.S. PHS, this committee extended the analysis of radon
daughters and cigarette use, which was carried out by Whittemore and
McMillan.38 The results of our analysis of 256 lung-cancer deaths are
summarized in Table VII-1 and presented in detail in Part 2 of this
appendix. They support Whittemore and McMillan's conclusions with
some qualifications. The multiplicative relative-risk model fit the data
quite well (P = 0.48), while the purely additive excess-relative-risk model
was rejected (P = 0.005~. To help clarify these results we studied a
larger class of models, which were defined through a mixture of competing
models,34 in which both the additive and multiplicative models were nested.
This investigation showed that the best-fitting model was submultiplicative,
although it did not provide a statistically significant improvement in fit over
the multiplicative model. The fitting of a sequence of models suggested
that the data are consistent with a wide range of submultiplicative to
supramultiplicative models, and there is no clear a prior reason to accept
the multiplicative model, except parsimony.
STUDIES AMONG NEW MEXICO URANIUM MINERS
In the second part of this appendix, an evaluation is presented of the
associations of cigarette smoking and duration of underground employ-
ment in a uranium mine with lung cancer in case-control data extracted
from a cohort of New Mexico uranium miners. The results (Table VII-1)
suggest that a multiplicative combination of the two exposures is more
OCR for page 553
RADON DAUGHTERS AND CIGARETTE SMOKING
TABLE VII-22 Lifetime Risk (Re) by Age Started and
Age Exposure Ends for Various Rates of Annual
Exposure a for Female Nonsmokers
Age (yr) Age (yr) Exposure Ends
Started 10 20 30 40 50 60 70 80 110
Exposure Rate = 0.10 (WLM/yr)
0 0.006 0.006 0.006 0.006 0.006 0.006 0.006 0.006 0.006
10 0.006 0.006 0.006 0.006 0.006 0.006 0.006 0.006
20 0.006 0.006 0.006 0.006 0.006 0.006 0.006
30 0.006 0.006 0.006 0.006 0.006 0.006
40 0.006 0.006 0.006 0.006 0.006
50 0.006 0.006 0.006 0.006
60 0.006 0.006 0.006
Exposure Rate = 0.20 (WLM/yr)
0 0.006 0.006 0.006 0.006 0.007 0.007 0.007 0.007 0.007
10 0.006 0.006 0.006 0.006 0.007 0.007 0.007 0.007
20 0.006 0.006 0.006 0.006 0.006 0.007 0.007
30 0.006 0.006 0.006 0.006 0.006 0.006
40 0.006 0.006 0.006 0.006 0.006
50 0.006 0.006 0.006 0.006
60 0.006 0.006 0.006
Exposure Rate = 0.50 (WLM/yr)
0 0.006 0.007 0.007 0.007 0.007 0.008 0.008 0.008 0.008
10 0.006 0.007 0.007 0.007 0.007 0.007 0.007 0.007
20 0.006 0.007 0.007 0.007 0.007 0.007 0.007
30 0.006 0.007 0.007 0.007 0.007 0.007
40 0.006 0.007 0.007 0.007 0.007
50 0.006 0.006 0.006 0.006
60 0.006 0.006 0.006
Exposure Rate = 1.00 (WLM/yr)
0 0.007 0.007 0.008 0.008 0.009 0.009 0.009 0.009 0.009
10 0.007 0.007 0.008 0.008 0.009 0.009 0.009 0.009
20 0.007 0.007 0.008 0.008 0.008 0.008 0.008
30 0.007 0.007 0.008 0.008 0.008 0.008
40 0.007 0.007 0.007 0.007 0.007
50 0.006 0.007 0.007 0.007
60 0.006 0.006 0.006
Exposure Rate = 4. 00 (WLM/yr)
0 0.008 0.010 0.012 0.014 0.017 0.018 0.019 0.020 0.020
10 0.008 0.010 0.012 0.015 0.016 0.017 0.018 0.018
20 0.008 0.010 0.013 0.014 0.015 0.016 0.016
30 0.008 0.011 0.012 0.013 0.014 0.014
40 0.008 0.010 0.011 0.011 0.011
50 0.008 0.009 0.009 0.009
60 0.007 0.007 0.007
553
OCR for page 554
554
TABLE VII-22 (Continued)
HEALTH RISKS OF RADON AND OTHER ALPHA-EAfITTERS
Age (yr) Age (yr) Exposure Ends
Started 10 20 30 40 50 60 70 80 110
Exposure Rate = 10.00 (WLM/yr)
0 0.011 0.016 0.021 0.026 0.032 0.036 0.038 0.039 0.040
10 0.011 0.016 0.022 0.027 0.032 0.034 0.035 0.035
20 0.011 0.017 0.022 0.027 0.029 0.030 0.030
30 0.012 0.017 0.022 0.024 0.025 0.025
40 0.012 0.016 0.018 0.019 0.020
50 0.010 0.013 0.014 0.014
60 0.008 0.009 0.010
Exposure Rate = 20. 00 (WLM/yr)
0 0.016 0.026 0.036 0.046 0.057 0.066 0.070 0.071 0.072
10 0.016 0.026 0.037 0.048 0.056 0.060 0.062 0.063
20 0.016 0.027 0.038 0.047 0.051 0.053 0.053
30 0.017 0.028 0.037 0.041 0.043 0.044
40 0.018 0.026 0.030 0.032 0.033
50 0.015 0.019 0.021 0.022
60 0.010 0.012 0.013
~ _ . _
a estimated with the committee's TSE model (Chapter 2) and a multiplicative interaction be-
tween smoking and exposure to radon progeny. Note that Re includes Ro, the calculated lifetime
risk for unexposed female nonsmokers, 0.00602.
OCR for page 555
RAD ON DA UGN~ERS AND CIGARE TTE SMOKING
TABLE VII-23 Years of Life Lost (Lo—Le) by Age
Started and Age Exposure Ends for Various Rates of
Annual Exposurea for Female Nonsmokers b
Age (yr) Age (yr) Exposure Ends
Started 10 20 30 40 50 60 70 80 110
555
Exposure Rate = 0.10 (WLM/yr)
0 0.00 0.00 0.00 0.00 0.01 0.01 0.01 0.01 0.01
10 0.00 0.00 0.00 0.00 0.00 0.01 0.01 0.01
20 0.OO 0.OO 0.OO 0.OO 0.OO COO 0 DO
30 0.00 0.00 0.00 0.00 0.00 0.00
40 0.00 0.00 0.00 0.00 0.00
50 0.00 0.00 0.00 0.00
60 0.OO 0.OO COO
Exposure Rate = 0.20 (WLM/yr)
0 0.00 0.00 0.01 0.01 0.01 0.01 0.01 0.01 0.01
10 0.00 0.00 0.01 0.01 0.01 0.01 0.01 0.01
20 0.00 0.00 0.01 0.01 0.01 0.01 0.01
30 0.00 0.00 0.01 0.01 0.01 0.01
40 0.00 0.00 0.00 0.00 0.00
50 0.00 0.00 0.00 0.00
60 0.OO COO COO
Exposure Rate = 0.50 (WLM/yr)
0 0.00 0.01 0.01 0.02 0.03 0.03 0.03 0.03 0.03
10 0.00 0.01 0.02 0.02 0.02 0.03 0.03 0.03
20 0.01 0.01 0.02 0.02 0.02 0.02 0.02
30 0.01 0.01 0.01 0.02 0.02 0.02
40 0.01 0.01 0.01 0.01 0.01
50 0.00 0.00 0.00 0.00
60 0.OO 0.OO 0.OO
Exposure Rate = 1. 00 (WLM/yr)
0 0.01 0.02 0.03 0.04 0.05 0.06 0.06 0.06 0.06
10 0.01 0.02 0.03 0.04 0.05 0.05 0.05 0.05
20 0.01 0.02 0.03 0.04 0.04 0.04 0.04
30 0.01 0.02 0.03 0.03 0.03 0.03
40 0.01 0.02 0.02 0.02 0.02
50 0.01 0.01 0.01 0.01
60 0.OO 0.OO 0.OO
Exposure Rate = 4. 00 (WLM/yr)
0 0.04 0.08 0.12 0.16 0.21 0.23 0.24 0.24 0.24
10 0.04 0.08 0.12 0.17 0.19 0.20 0.20 0.20
20 0.04 0.09 0.13 0.16 0.16 0.16 0.16
30 0.05 0.09 0.12 0.12 0.12 0.12
40 0.04 0.07 0.08 0.08 0.08
50 0.03 0.03 0.03 0.03
60 0.01 0.01 0.01
OCR for page 556
556
TABLE VII-23 (Continued )
llE~LTH RISKS OF RADON AND OTHER ALPNA-EAHI~R.S
Age (yr) Age (yr) Exposure Ends
Started
10 20
10
20
30
40
50
60
o
10
20
30
40
so
60
Estimated with the committee's TSE model (Chapter 2) and a multiplicative interaction be-
tween smoking and exposure to radon progeny.
bR<,, the calculated lifetime risk for unexposed female nonsm`,kers,; is 76.7 yr.
30 40 50 60 70
0.10 0.20
0.10
0.20 0.39
0.19
80
Exposure Rate = 10.00 (WLM/yr)
0.29 0.41 0.s2 0.58 0.60 0.60
0.20 0.31 0.42 0.48 0.50 o.so
0.10 0.21 0.32 0.39 0.41 0.4
0.11 0.22 0.29 0.31 0.31
0.11 0.18 0.20 0.20
0.07 0.08 o.og
0.02 0.02
Exposure Rate = 20. 00 {WLM/yr)
o.s' 0.81 1.02 1.15 1.18
0.39 0.62 0.83 0.96 0.99
0.20 0.42 0.64 0.77 0.8
0.22 0.45 0.s7 0.61
0.22 0.3s 0.39
0.13 0.17
0.04
110
0.60
o.so
0.40
0.31
0.19
0.08
0.02
.19
1.00
0.8
0.62 0.61
0.39 0.39
0.17 0.17
0.04 0.03
1.18
o.ss
0.80
OCR for page 557
RADON DAUGHTERS AND CIGARETTE SMOKING
PART S. Further Considerations
EFFECTS OF CIGARETTE SMOKING ON THE
RESPIRATORY TRACT
557
Cigarette smoking has well-characterized effects at all levels of the res-
piratory tract (Table VII-24.3 Changes in the airways axe most relevant
for respiratory carcinogenesis. Cigarette smoking produces mucus gland
hypertrophy and hyperplasia in the large airways and stimulates mucus
production from goblet cells in the small airways. The clinical counter-
part of these changes is chronic bronchitis, defined as regular sputum
production. The bronchial epithelium develops dysplastic and metaplas-
tic changes in smokers. Certain physiological changes accompany these
structural abnormalities. Mucociliary clearance, which removes gases and
particles from the large airways, is slowed in cigarette smokers. Increased
permeability may facilitate passage of inhaled agents across the epithelium.
Proportionately greater central deposition of particles has been demon-
strated in the airways of smokers, in comparison with nonsmokers. This
deposition pattern may be a consequence of the abnormal small airway
function commonly found in smokers. Impaired lung function can be
demonstrated in many smokers, and perhaps 10 to 15% of sustained smok-
ers develop disabling chronic airflow obstruction. The resulting physiolog-
ical impairment leads to an increased respiratory rate for any particular
level of activity.
TABLE VII-24 Histologic and Physiologic Changes
in the Respiratory Tract, Other than Malignancy,
Associated with Cigarette Smoking36
Large airways
Small airways
Lung parenchyma
Mucous gland hypertrophy and hyperplasia
Dysplasia and metaplasia of epithelial cells
Increased epithelial permeability
Impaired mucociliary transport
Inflammation
Goblet cell metaplasia
Epithelial cell metaplasia
Increased mucus production
Inflammation
Fibrosis
Increased cell numbers
Altered cell populations
Altered function of some cells
Emphysema
OCR for page 558
558
HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTERS
In assessing the consequences of combined exposure to cigarette smoke
and radon daughters, consideration must be given to these diverse erects
of smoking (Table VII-24), as well as to interaction between the two
agents in the process of carcinogenesis itself. Smoking-related changes
in the lung's structure and function might alter the dose to target cells
at any particular level of exposure. In comparison with nonsmokers,
dose might be increased in smokers by the greater central deposition, the
increased airways permeability, and the slowed mucociliary transport. Dose
might be reduced in smokers by mucosal edema and the increased average
mucus thickness due to the heightened mucus production in the airways of
smokers. A conclusion concerning the net effect of these smoking-related
changes on the dosimetry of radon daughters cannot be reached at present.
Nevertheless, the eBect of radon daughters in the presence of smoking must
be interpreted in the context of the changes in lung structure and function,
which can be readily demonstrated in many smokers.36
In this regard, several pulmonary disease processes resulting from
cigarette smoking have been associated with increased lung-cancer risk:
chronic bronchitis and chronic obstructive pulmonary disease. By epidemi-
ological convention, chronic bronchitis refers to chronic sputum production.
Clinical diagnosis of chronic obstructive pulmonary disease occurs in pa-
tients with disabling and irreversible airflow obstruction. At times, clinical
diagnoses such as chronic bronchitis, emphysema, and chronic obstruc-
tive pulmonary disease may be applied to persons with irreversible airflow
obstruction, regardless of other features.
Nevertheless, epidemiological studies show that these diagnoses are
associated with increased risk of lung cancer, even with adjustment for
cigarette smoking. In an early case-control study, Doll and Hilli3 found
that lung-cancer cases yield a history of chronic bronchitis significantly
more often than controls. In two subsequent case-control studies, diag-
nostic terms applied to patients with chronic airflow obstruction were also
associated with lung cancer, even with control for cigarette smoking.33~37
Davisi2 showed that the incidence of lung cancer in patients with chronic
obstructive pulmonary disease was higher than expected in comparison
with rates in smokers.
Two studies have demonstrated that mucus hypersecretion, as as-
certained by a questionnaire, predicts increased lung-cancer occurrence.
Rimington29 determined lung-cancer incidence in male participants who
had given information on their smoking habits and sputum production for
a radiological screening program. In all categories of cigarette smoking,
lung-cancer incidence was higher in those with a history of daily sputum
production for 5 yr at the time of enrollment. Peto et al.25 examined
mortality of 2,518 British men during a 2OL to 25-yr follow-up period.
OCR for page 559
RADON DAUGHTERS AND CIGARETTE SMOKING
559
Lung-cancer mortality was higher in those with a lower level of lung func-
tion and in those with chronic sputum production. The latter association
persisted after adjustment for lung-function level and cigarette smoking.
The finding of increased lung cancer in persons with underlying respira-
tory disease and mucus hypersecretion conflicts with the hypothesis that
increased mucus production reduces penetration of alpha particles into the
tracheobronchial epithelium and thus protects against cellular damage.3
THE ASSOCIATION BETWEEN LUNG CANCER, SMOKING,
AND RADIATION
Exposure to radon progeny and cigarette consumption are each asso-
ciated with lung cancer in a complex way. Because there are only a few
studies on the combined effects of radiation exposure and tobacco smoke,
the amount of information for their interaction is limited. The commit-
tee's analyses described in Chapter 2 and Annex 2A show that cancer
risk associated with exposure to radon progeny depends on cumulative
dose, age, and time since exposure. The actual biological relationship is
undoubtedly more complex than the statistical model that the committee
has developed and may be influenced by other factors that cannot be fully
evaluated with the available data. These factors might include age at first
exposure, dose rate, sex, diet, and genetic predisposition. Moreover, the
association of tobacco consumption with lung cancer is also complex and
depends on duration and number of cigarettes smoked per day, type of
tobacco product, method of inhalation, and years since cessation of use for
former smokers.35 Assessment of the combined effects of cigarette smoking
and radon progeny should account for the individual patterns of effect
from both insults. Other aspects of the combined exposure may also be
important, for example, the effect of the sequencing of exposures and the
degree of their overlap in time.
In contrast, the studies of combined exposures, reported in the litera-
ture or analyzed by this committee in Part 2 of this appendix, have usually
considered only cumulative WLM (or duration of employment or other
surrogate) and duration or intensity of cigarette use, and not the effects
of the other variables described above. Such assessments of the underlying
relationship may be distorted by not accounting for other predictors of
risk. Nevertheless, risk models are a useful method for describing patterns
in the different data sets. With these complexities in mind, the data
currently available on radon daughters and tobacco exposure suggest that
risks do not combine additively on the relative-risk scale. Although there
is great uncertainty regarding the relative impact of the two exposures,
the multiplicative model appears to have greater support in the literature.
The analyses by this committee suggest that a submultiplicative model
OCR for page 560
560
HEALlrH RISKS OF RADON AND OTHER ALPHA-13MITTERS
should not be dismissed and may provide a more accurate description of
the underlying relationship.
A clear pattern of risk among studies of miner's exposure to radon
and tobacco smoke has not yet emerged. A few small studies have shown
mixed results, while the largest study of the msue by Whittemore and
McMillan38 indicates a multiplicative interaction. While the committee's
analyses of the Colorado Plateau uranium miners In Part 2 of this appendix
support this conclusion, the analyses also support submultiplicative and
supramultiplicative relationships.
The committee's analysis of the Japanese atomic-bomb survivor data
shows that for these data, neither an additive nor a multiplicative model
can be rejected on statistical grounds; indeed, their magnum likelihoods
are nearly identical. This is consistent with the results of Prentice et al.26
In summary, the atomic-bomb survivor data appear amenable to either a
multiplicative or additive model for the relative risk. The most recent case-
control study by Blot et al.6 based on a large number of lung-cancer cases
sustains this interpretation. The relevance of these studies of atomic-bomb
survivors to the interaction of radon and smoking in their relationship to
lung-caDcer induction, however, must still be determined.
Our review suggests that this issue has yet to be resolved. Areas for
further study that are needed to clarify the combined effect of these two
exposures include the following:
.
the impact of smoking rate (cigarettes per day) and smoking
duration, as opposed to rate and/or the combined pack-years, on the
radiation association with lung cancer;
implications of low- versus high-LET radiation;
the role of smoking cessation on the effect of radiation-associated
lung cancer;
.
exposure;
the effect on interactions of tobacco use before and after radiation
· the role of cigarette use on the histological distribution of radiation-
associated lung cancer;
· the relationship of smoking to other measures of radiation expm
sure, for example, working-level rate, cumulative WLM, and duration of
exposure; and
· the role of other agents associated with lung diseases, such as
asbestos, silica, and arsenic.
REFERENCES
1. Archer, V. E., J. K. Wagoner, and F. E. Lundin. 1973. Uranium mining and
cigarette smoking effects on man. J. Occup. Med. 15:204-211.
OCR for page 561
RAD ON DA UGHTERS AND CIGARE TTE SMOKING
561
2. Axelson, O. 1983. Experiences and concerns on lung cancer and radon daughter
exposure in mines and dwellings in Sweden. Z. Erkrank. Atm.-Org. 161:232-239.
3. Abelson, O., and L. Sundell. 1978. Mining lung cancer and smoking. Scand. J.
Work Environ. Health 4:46-52.
4. Band, P., M. Feldstein, G. Saccomanno, L. Watson, and O. King. 1980.
Potentation of cigarette smoking and radiation: Evidence from a sputum cytology
survey among uranium miners and controls. Cancer 45:1273-1277.
5. Beebe, W. G., and M. Usagawa. 1968. The major ABCC samples. Pp. 12-68
in Atomic Bomb Casualty Commission Technical Report. Hiroshima, Japan:
Atomic Bomb Casualty Commission.
6. Blot, W. J., S. Akiba, and H. Kato. 1984. Ionizing radiation and lung cancer:
A review including preliminary results from a case-control study among A-bomb
survivors. In Atomic Bomb Survivor Data: Utilization and Analysis, R. L.
Prentice and D. J. Thompson, eds. Philadelphia: Society for Industrial and
Applied Mathematics.
7. Breslow, N. E., and B. E. Storer. 1985. General relative risk functions for case
control studies. Am. J. Epidemiol. 122:149-162.
8. Cederlof, R., L. Friberg, Z. Hrubec, and U. Lorich. 1975. The relationship of
smoking and some covariables to mortality and cancer morbidity. Report of the
Department of Environmental Hygiene. Stockholm: Karolinaka Institute.
9. Cox, D. R. 1972. Regression models and life tables (with discussion). J. R. Stat.
Soc. Ser. B 34:187-220.
10. Damber, L., and L. G. Larsson. 1982. Combined effects of mining and smoking
in the causation of lung carcinoma. Acta Radial. Oncol. 21:305-313.
11. Damber, L., and L. G. Lareson. 1985. Underground mining, smoking, and lung
cancer: A case-control study in the iron ore municipalities in Northern Sweden.
J. Natl. Cancer Inst. 74:1207-1213.
12. Davis, A. L. 1976. Bronchogenic carcinoma in chronic obstructive pulmonary
disease. J. Am. Med. Assoc. 235:612-622.
13. Doll, R., and A. El. Hill. 1952. A study of the aetiology of carcinoma of the
lung. Br. Med. J. 2:1271-1286.
14. Edling, C., H. Kling, and O. Axelson. 1984. Radon in homes—a possible cause
of lung cancer. Scand. J. Work Environ. Health 10:25-34.
15. Hornung, R. W., and S. Samuels. 1981. Survivorship models for lung cancer
mortality in uranium miners is cumulative dose an appropriate measure of
exposure? Pp. 363-368 in Radiation Hazards in Mining: Control, Measurement
and Medical Aspects, M. Comes, ed. New York: Society of Mining Engineers of
the American Institute of Mining Metallurgical and Petroleum Engineers.
16. Ishimara, T., R. W. Cihak, C. E. Land, A. Steer, and A. Yamada. 1975. Lung
cancer at autopsy in A-bomb survivors and controls, Hiroshima and Nagasaki,
1961-1970. II. Smoking, occupation and A-bomb exposure. Cancer 36:1723-1728.
17. Jorgensen, H. S. 1973. A study of mortality from lung cancer among miners in
Kiruna 195~1970. Scand. J. Work. Environ. Health 10:120133.
18. Kato, H., K. G. Johnson, and K. Yano. 1966. Mail survey of cardiovascular
disease study, Hiroshima and Nagasaki. Pp. 1066 in Atomic Bomb Casualty
Commission Technical Report.
Commission.
Hiroshima, Japan: Atomic Bomb Casualty
19. Kopecky, K. J., T. Yamamoto, T. Fujikura, S. Tokuoka, T. Monzen, I. Nishimari,
E. Nakashima, and H. Kato. In press. Lung cancer, radiation exposure and
smoking among A-bomb survivors, Hiroshima and Nagasaki, 1950-1980. In press.
Techincal Report. Hiroshima, Japan: Radiation Effects Research Foundation.
OCR for page 562
562
HEALTH RISKS OF RADON AND OTHER ALPHA-EMITTERS
20. Liddell, F. D. K., J. C. McDonald, and D. C. Thomas. 1977. Methods of cohort
analysis: Appraisals by application to asbestos mining. J. R. Stat. Soc. Ser. A
140:469091.
21. Lubin, J. H., and M. H. Gail. 1984. Biased selection of controls for ca~e-control
analyses of cohort studies. Biometrics 40:63-75.
22. Lundin, F. E., Jr., V. E. Archer, and J. K. Wagoner. 1979. An exposure-
time-response model for lung cancer mortality in uranium miners effects of
radiation exposure, age and cigarette smoking. Pp. 243-264 in Proceedings of
the Work Group at the Second Conference of the Society for Industrial and
Applied Mathematics, N. E. Breslow, and A. Whittemore, eds.
23. Morgan, M.V. and J. M. Samet. 1986. Randon daughter exposures of New
Mexico U miners, 1967-1982. Health Phye. 50:65~662.
24. National Institute for Occupational Safety and Health (NIOSH). 1986. Evaluation
of Epidemiologic Studies Examining the Lung Cancer Mortality of Underground
Miners. Division of Standards Development and Technology Transfer. Cincinnati,
Ohio: Centers for Disease Control, National Institute for Occupational Safety
and Health.
25. Peto, R., F. E. Speizer, A. L. Cochrane, F. Moore, C. M. Fletcher, C. M.
Tinker, I. T. Higgins, R. G. Gray, S. M. Richards, J. Gilliland and B. Norman-
Smith. 1983. The relevance in adults of air-flow obstruction, but not mucus
hypereecretion to mortality from chronic lung disease: Results from 20 years of
prospective observation. Am. Rev. Respir. Die. 128:491-501.
26. Prentice, R. L., Y. Yoshimoto, and M. Mason. 1983. Relationship of cigarette
smoking and radiation exposure to cancer mortality in Hiroshima and Nagasaki.
J. Natl. Cancer Inst. 70:611-622.
27. Radford, E. P., and K. G. St. Clair Renard. 1984. Lung cancer in Swedish
iron ore miners exposed to low doses of radon daughters. N. Engl. J. Med.
310~23~:1485-1494.
28. Renard, K. G. St. Clair. 1974. Respiratory cancer mortality in an iron ore mine
in Northern Sweden. Ambio. 3:67-69.
29. Rimington, J. 1971. Smoking chronic bronchitis and lung cancer. Br. Med. J.
2:37~375.
30. Rok~ranor i Sverige. 1965. Report of the Central Statistical Bureau. Stockholm:
Central Statistical Bureau.
31. Saccomanno, G., V. E. Archer, O. Auerbach, R. P. Saunders, and L. M.
Brennan. 1974. Development of carcinoma of the lung as reflected in exfoliated
cells. Cancer 33:256-270.
Saccomanno, G., C. Yale, W. Dixon, O. Auerbach, and G. C. Huth. 1986.
An epidemiological analysis of the relationship between exposure to Rn progeny,
smoking and bronchogenic carcinoma in the U-mining population of the Colorado
Plateau 1960-1980. Health Phys. 50:605-618.
33. Samet J. M., C. G. Humble, and D. R. Pathok. 1986. Personal and family history
of respiratory disease and lung cancer risk. Am. Rev. Respir. Dis. 134:466-470.
34. Thomas, D. C. 1981. General relative risk models for survival time in matched
case-control analysis. Biometrics 37:673-686.
35. U.S. Department of Health and Human Services, U.S. Public Health Services
Office of Smoking and Health. 1972. The Health Consequences of Smoking:
Cancer. A report to the Surgeon General. Department of Health and Human
Services (PHS) 82-50179 Washington D.C.: U.S. Government Printing Office.
36. U.S. Department of Health and Human Services, U.S. Public Health Service,
Office of Smoking and Health. 1985. The Health Consequences of Smoking:
OCR for page 563
RADON DAUGHTERS AND CIGARETTE SMOKING
563
Chronic Obstructive Lung Disease. A Report to the Surgeon General. PHS
85-50207. Washington, D.C.: U.S. Government Printing Office.
37. Van der Wal, A.M., E. Huizingav, N.G. Orie, H.S. Sliuter, and K.de Vries. 1966.
Cancer and chronic nonspecific lung disease (C.N.S.L.D.~. Scand. J. Respir. Die.
47:161-172.
38. Whittemore, A. S., and A. McMillan. 1983. Lung cancer mortality among U.S.
uranium miners: A reappraisal. J. Natl. Cancer Inst. 71:489-499.
Representative terms from entire chapter:
cigarette smoking
