Lorillard
Exposure to Environmental Tobacco Smoke and Risk of Lung Cancer in Non-Smoking Women From Moscow, Russia
Fields
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- Aitakov, Z.N.
- Boffetta, P.
- Maximovitch, D.
- Zaridze, D.
- Zemlyanaya, G.
- Boffetta, P.
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- COGGINS,CHRIS/OFFICE
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- Int J Cancer
- Intl Agency for Research on Cancer
- Intl Union Against Cancer
- Rams Nn Blokhin Cancer Research Centre
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- Wiley Liss
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PASSIVE SMOKING AND LUNG CANCER 337
TABt.E 14'- ASSOC]At lON nETW ISEN R1SK OF ADENOCARCINOMA AND OF SQUAMOUS-CELL CANCER OF TnE I UNG
AND PASSIb'li SMOKING
Ade.nnearelnnn,a Squamous-cdl lung cancer
Smoking Tabfl Convols C ves
ox'
95°mCI ConcroLs C:axe.e
OR'
959oCI
n-35R n=1n6 n=35R n-42
Husband's smoking
no
195
46
1.0
195
16
1.0
yes 163 60 152 Q96-2.39 163 26 1.94 0.99-3.81
Smoking of other member of a household
no
285
84
1.0
285
37
1.0
yes 73 22 0.98 0.57-1.70 73 5 0.48 0.18-1.29
Colleagues' smoking
no
291
84
1.0
291
32
1.0
yes 67 22 0.99 0.56-1.73 67 10 1.20 0.54-2.63
Father's smoking
no
180
54
1.0
180
19
1.0
yes 178 52 Q9l 0.58-1.42 178 23 1.14 0.59-2.19
Husband's smoking, type of cigarettes
no
195
46
1.0
195
16
1.0
filter 72 13 0.74 037-1.48 72 6 1.08 0.40.2.91
no filter 32 15 2.00 0.96-4.16 32 4 1.50 045-5.01
"papirosy" 59 32 2.34 L32-4.14 59 16 3.13 1.44-6.81
t
'OR adjusted for age and education.
expected that some association may exist with passive smoking as
well. Therefore, we conducted logistic-regression analysis using 2
sub-sets of the control group (i) patients with breast and endome-
trial cancer, and (ii) other controls.
Using as controls breast-cancer and endometrial-cancer patients
only did not materially alter the results, although the estimated OR
were somewhat higher. Husbands' smoking was associated with a
statistically significant increase of lung cancer in non-smoking
wonten (OR, 1.82; 95% Cl, 1 J 8-2$0). Using other controls in the
logistic-regression model showed sonlewhat weaker association
with the exposure to ETS from husband (OR, 1.22; 95% CI,
0.79-1.88).
DISCUSSION
The main importance of our study is that it is conducted on a
population with a specific snloking pattern from which no informa-
tion is available on the health effects of ETS. Another strong aspect
of the study is its size, which made it possible to separate sizeable
groups of cases and controls with high exposure to ETS, and to
conduct analyses for different histological types of lung cancer.
The United States Department of Health and Human Services
(DHHS) Environmental Protection Agency (EPA) has classified
ETS as aa known human lung carcinogen, on the basis of the
numerous carcinogens found both in ETS and in mainstream
tobacco smoke (IARC, 1985), and of the higher lung-cancer risk
seen in ncver-smokers exposed to ETS in epidemiological studies
(US DHHS, 1993).
Most of these studies concentrated on ETS exposure from
spouse's smoking. However, some of them addressed other sources
of ETS exposure, such as parents during childhood, household
members other than the husband, work environment (US Public
Health Service, 1986: National Research Council, 1986; Persha-
gen, 1994; Tredaniel et al., 1994).
Typically elevated risks of lung cancer were observed in
non-smoking women living with smoking men: relative risk (RR)
ranged from 1.2 (Brownson et al., 1992; Fontham et a(., 1994) to
3.2 (Pershagen et al., 1987). The meta-analyses performed esti-
mated that the RR of lung cancer for non-smoking women living
with smoking men was around 1.3 (US Public Health Service.
1986; National Research Council, 1986; Blot and Fraumeni, 1986;
Wald et ai., 1986; Saracci and Riboli. 1989).
Six studies on risk of lung cancer from spouse's smoke are
available from Europe: 2 from Greece (Trichopoulos et al., 1983;
Kalandidi et al., 1990) showed a 2-fold increased risk. Of the other
studies, only the last study from Sweden (Pershagen et al., 1987)
found an increased risk of lung cancer above 45 pack-years of
exposure. Two meta-analyses of this data are available. Pershagen
(1994) combined 6 studies and estimated an overall RR of 1.47
(95% Cl, 1.12-1.92), while the US DHHS (1993) excluded the
Greek studies and calculated a combined RR of 1.17 (95% CI,
0.84-1.62).
Our summary OR of 1.53 (95% CI 1.06-2.21) is compatible with
cstimates from the meta-analysis of Pershagen (1994), although it
suggests that the effect of ETS from spouses in Russia is somehow
stronger than in Western Europe.
The evidence from the available studies of an association
between P.TS exposure during childhood and lung-cancer risk is
inconsistent (Pershagen, 1994). Two large studies from the United
States reported no increased risk from childhood exposure (Brown-
son et aL, 1992; Fontham et al., 1994). In our study we failed to
find any association between ETS exposure in childhood and risk
of lung cancer in non-smoking women.
Our data indicating no effect of workplace exposure to ETS on
the risk of lung cancer are in concordance with studies from Europe
(Pershagen, 1994). However, in some other studies (Fontham et aL,
1994) RR associated with workplace exposure was higher than that
associated with exposure to husband's smoking.
Increased relative risk of lung cancer was observed with
increasing pack-years of exposure to ETS of the husband (Fnntham
et al., 1994) and number of cigarettes per day smoked by him
(Cardenas et aL, 1997). We have also studied the association
between number of cigarettes smoked and duration of smoking and
risk of lung cancer. However, the increase in risk was not uniform.
Our study suggests that the association between exposure to
husbands' smoking and risk of lung cancer in non-smoking women
is somewhat stronger for squamous-ecll carcinoma (OR, 1.94; 95%
CI, 0.99-3.81) than for adenocarcinonla (OR, 152; 95% Cf,
0.9(-2 39). Similar results were obtained in other studies on ETS
conducted in Europe (Trichopoulos et al., 1983; Pershagen el al.,
1987; Kalandidi et al, 1990) and in the United States (Fontham et
al., 1994). This result parallels the stronger association found
between active smoking and squamous-cell lung carcinoma as
compared with adenocarcinoma.
We report an association between type of cigarettes smoked by
the husband and lungcancer risk. The risk is higher For women
whose husbands smoke "papirosy' than for women whose hus-
bands smoke cigarettes without filter. This association is stronger
for women with squamous-cell carcinoma than for those with
adenocarcinoma- In fact, we found no increase in risk of lung

336
RESULTS
ZARIDZE EIAL
Table I shows the distribution of demographic characteristics.
Cases were somewhat older than controls at disease occurrence or
interview. Crude occupational classification of cases and controls
was similar. Cases were less educated than controls (p = 0.001).
There was also a significant difference in marital status between
cases and controls (p = 0.03). Among cases, there were more
widows than among controls.
Among lung-cancer cases, the majority (56.1%) were adenocar-
cinoma, while 22.2% of cases were squamous-cell cancer, and
5.3% small-cell carcinoma (Table ID.
Diseases among the control women included breast cancer
(39.7%), melanoma (20.4%), cancer of the endometrium (10.3%),
ovary (7.8%), stomach (4.5%) and uterine cervix (45%), also
Hodgkin's disease (5.3%), and other cancers (7.0%) (Table II).
Table III presents OR of lung cancer in non-smoking women
associated with exposure to ETS. An elevated risk of lung cancer
was identified in women whose husbands smoked. The OR
adjusted by age and education for husbands smoking was 1.53
(95% CI, 1.06-2.21). Smoking by other members of the family, by
colleague or by father during childhood of index patient did not
affect the risk of lung cancer.
Additional analyses nsing qualitative and quantitative variables
for husband's smoking practices showed, that the OR is affected by
the type of cigarettes: OR for smoking cigarettes without filter was
1.74 (95% CI, 0.94-3.20). Smoking "papirosy" was associated
with a statistically significant increase in risk (OR, 2.12; 95% CI,
TABLE I-DESCRIPTIVE D ATA FOR FEMALE LUNG-CANCER
CASES AND CONTROLS'
Y]nbe Controls, k
(N=358) Cases, Ho
(N=189) p
vNuc
Age at interview
<55
25.7
23.8
0.14
55-65 39.4 32.8
>65 34.9 43.4
Marital status
married
50.8
47.6
0-03
divorced 16.2 11.1
never married
widowed 7.0
26.0 4.2
37.1
Educational level
sohool(notcompleted)
25.4
27.0
0.001
secondary school 36.0 49.7
some university 38.6 23.3
Occupational classification
manual worker
38.3
42.3
0.36
office worker 61.7 57.7
IAll subjects were life-long non-smokers and had lived in Moscow
for 20 years or more prior to interview.
TABLE II-DIS'1'RIBUTION OF LUNG-CANCER CASES BY HISTOLOOICALTYPE
AND CONTROLS BY SITE OF PRIMARY TUMOR
Cases Controts
FG.ttMogiu,I type Numbrs `,5 Site Number °h
Adenocarcinoma 106 56.1 Breast 142 39.7
Squatnous-cell
i 42 22.2 Melanoma 73 20.4
carc
noma
Small-cell card-
10
5.3 Endometrium
37
10.3
noma
Large-eell carci-
2
1.1 Ovary
28
7.8
noma
Mixed 7 3.7 Stomach 18 5.0
Others(carcinoid) 5 2.6 Cervix ulari 16 4.5
Unknown 17 9.0 Hodkin's 19 5.3
disease
Others
25
7.0
Total 189 100.0 Total 358 100.0
TABLE III-ASSOCIATION BETWEEN RISK OF LUNG CANCER
AND PASSIVE SMOKING
Smnkingbabit Contmis
n=358 Orses
n=189 OR' 959oCI Trend
Husband's smoking
no
195
80
1.0
yes 163 109 1.53 1.06-2.21
Smoking of other member
of a household
no
285
151
1.0
yes 73 38 0.91 0.58-1.42
Colleagues' smoking
no
291
153
1.0
yes 67 36 0.88 0.55-1.41
Father's smoking
no
180
97
1.0
yes 178 92 0.92 0.64-1.32
Husband's smoking, dura-
tion (years)
no
195
80
1.0
0.07
1-15 39 31 1.86 1.07-3.22
>15 124, 78 1.42 0.95-2.12
Husband's smoking,
quantity of cigarettes
no
195
80
1.0
0.10
1-10 90 66 1.66 1.09-2.52
>10 73 43 1.35 0.84-2.18
Husband's smoking, type
of cigarettes
no
195
80
1.0
filter 72 28 0.95 0.56-1.61
no filter 32 25 1.74 0.94-3.20
"papirosy 59 56 2.12 L32-3.40
Husband's smoking in
wife's presence
195
80
1.0
no 47 31 1.48 056-2.53
yes 116 78 1.55 1.04-2.31
'OR adjusted for age and education.
1.32-3.40). Husband's smoking in the wife's presence showed an
OR similar to any smoking (OR, 1.55, 95% CI, 1.04-2.31).
When husband's smoking was analyzed according to duration,
lung-cancer risk was elevated both for short- and for long-term
consumption, but there was no uniform increase in risk. Similarly,
an increase in risk was present among wives of smokers of 1 to 10
and more than 10 cigarettes per day, but the risk was higher in the
first than in the second category of consumption.
Risk of lung adenocarcinoma was also found to be associated
with husbands smoking (OR, 1.52; 95% CI, 0.96-2.39). No effect
was present for ETS from family members other than the husband,
workmates or the father. Risk was affected by the type of cigarettes
smoked by the husband. OR was 2.0 (95% CI, 0.96-4.16) for
husbands smoking cigarettes without filter and 2.34 (95% CI,
1.32-4.14) for husbands smoking "papirosy", ["Papirosy" are a
special type of Russian cigarettes with a long mouth piece; they
usually have very high levels of tar (higher than 30 mg/cig) and
nicotine (higher than 1.8 mg/cig) (Zaridze et at., 1986).) (Table IV).
The association between husbands' smoking and risk of squa-
mous-cell carcinoma in non-smoking women is somewhat stronger
than for all lung cancer combined or for adenocarcinoma OR for
husbands smoking is 1.94 (95% CI, 0,99-3.81) (Table IV). There is
a strong association between type of cigarettes smoked and risk of
squamous-cell cancer. OR for husband's smoking of cigarettes
without filter is 1.50 (95% CI, 0.45-5.01), for smoking "papirosy"
is 3.13 (95% CI, 1.44-6.81). Also for squamous-cell carcinoma,
there was no effect of ETS from sources other than the husband.
The other histological types were not numerous enough to allow
separate analyses. -
In this study, cancer patients were used as controls. The risk for
some of the cancer sites, such as cancer of the stomach and uterine
cervix, has been associated with active smoking and it may be
!
99035513

Int. J. Cancer: 75, 335-338 (1998)
© 1998 Wiley-Liss, Inc.
Publlcatlon of the International Union Against Cancer
Publication de Union In[ernaVOnale Contre Ie Cancer
EXPOSURE TO ENVIRONMENTAL TOBACCO SMOKE AND RISK OF LUNG
CANCER IN NON-SMOKING WOMEN FROM MOSCOW, RUSSIA
David Za.rzmzE'*, Dimitri MnxLMovtTcta1, Galina ZEMC,YArrAYA', Zailil N. AtTAxov' and Paolo
BoFFgrrAZ i
tDeparhnentof'EpidemiologyandPreventlon,InstituteofCarcinogenests,RAMSAtN.BloklsinCancerResearchCent
re, _
Moscow, Russia 2Unit ofEnvironmental Epidemiology, International Agency for Research on Caacer,
Lyon, France
kq l:
The association between exposure to ETS and the risk of
lung cancer in life-time non-smoking women was investigated
by means of a hospital based case-control study in Moscow,
Russia. The main importance of our study is that it was
conducted on a population with a specific smoking pattern
from which no information is available on health effects of
ETS. A total of 189 incident cases of histologically confirmed
lung cancer were identified in 2 principal cancer treatment
hospitals in Moscow. A total of 358 female oncology patients
from the same hospitals were selected as controls. The
controls matched by the hospitals to the cases were similarly
restricted to never-smokers. Women diagnosed with cancer
of the upper respiratory organs were ineligible for selection
as controls. Personal interviews of cases and controls were
conducted in the hospital wards, using a closed-form struc-
tured questionnaire. An elevated risk of lung cancer was
observed in women whose husbands smoked. The odds ratio
(OR) adjusted by age and education for husband's smoking
was 1.53 (95% Cl, 1.06-2.21). Smoking by other members of
the family, by colleague's, or by fathers in the women's
childhood do not affect the risk of lung cancer. The risk is
higher for women whose husbands smoke "papirosy" (OR
2.12; 95% Cl, 1.32-3.40), a special Russian type of cigarettes
with a long mouthpiece, and usually very high levels of tar
(>30 mg/cig) and nicotine (> 1.8 mg/cig). Our study suggests
that thb association between exposure to ETS of the spouse
and risk of lung cancer in non-smoking women is somewhat
stronger for squamous-cell carcinoma (OR, 1.94; 95% Cl,
0.99-3.81) than for adenocarcinoma (OR, 1.52; 95% Cl, 0.96-
2.39). Int. f. Cancer 75:335-338, 1998.
© 1998 4i91ey-Liss, Inc.
Lung cancer is the most common malignant neoplasm in
developed countries (Parkin et al., '1992), including Russia (Zaridze
and Gurevicius, 7.986). Tobacco smoking being the main cause of
this fatal disease, responsible for an estimated 90 to 95% of
lung-cancer cases in men and 80 to 859o in women (TARC, 1985;
Petoetal., 1994).
Research on the hazards of smoking has turned recently to the
association between exposure to environmental tobacco smoke
(ETS) and adverse health events, itlcluding lung cancer. The
ubiquitousness of tobacco smoke in homes, work places and public
areas makes exposure to ETS virtually unavoidable. According to
different studies, 39 to 63% of the non-smoking population is
exposed to ETS (Friedman et al, 1983; Lebowitz et al., 1992).
Epidemiological studies have provided evidence of a causal
association between ETS and lung cancer ("Iredaniel et al., 1994;
Pershagen, 7994). The increase in relative risk of lung cancer
associated with ETS was typically observed in lifelong non-
smoking women living with a smoking spouse. The results suggest
that non-smokers exposed to ETS have an estimated 35% increased
risk of lung cancer, as compared with non-smokers not exposed
to ETS.
The available studies, though consistent in the overallresultc, are
in trtost cases too small in size to precisely quantify the magnitude
of the effect and to address the dose-response relationship and the
interaction with other risk factors for lung cancer. Moreover, no
studies are available from Eastern Europe, and specifically from
Russia, where the features of tobacco smoking are different from
countries in which the effects of ETS on the risk of lung cancer
have been studied.
We here report the results of a hospital-based case-control study
of lung cancer in lifetime non-smoking women residents of
Moscow city.
MATERIAL AND METHODS
The sources of subjects for this study were the Moscow City
Oncology Hospital and Cancer Research Center, 2 principal cancer
treatment hospitals in Moscow. Cases consisted of all women with
histologically confirmed primary carcinoma of the lung who were
admitted to the hospital or who were treated at outpatient clinics at
either of these facilities. An uniform histopathology review was
undertaken to confirm diagnosis of primary lung cancer and to
assess histology. For this study, cases were restricted to women
who had never smoked cigarettes and who lived inMnscow city. A
total of 189 incident cases were identifierl Because of weekly
hospital contacts, all cases were interviewed within 2 or 3 days of
admission to the hospital, before the start of any treatment.
A total of 358 female oncology patients from the same hospitals
were selected as controls. The control women matched by hospital
to the cases were similarly restricted to never-smokers and Moscow
residents. Women diagnosed with cancer of the upper respiratory
organs were ineligible for selection as controls.
In-person interviews of cases and controls were conducted in the
hospital wards using a closed form, structured questionnaire. Data
were collected on demographic characteristics (education and
marital status), residential history, housing characteristics, oecupa-
taoual history and ETS exposure, Occupational history included
data on location, duration and potential deleterious exposures for
all jobs within the last 20 years. Information on family history of
cancer was also obtained. The conrpliance rate for both cases and
controls was 100%.
Information on ETS was derived from questions on smoking
habits of the husband, other members of the household, and
smoking habits of collegues at the work place. In addition,
information on ETS exposure in childhood was sought by asking
about parental smoking habits.
Initially, occupational exposure was assessed by job title and
listing possible carcinogenic exposures. However, few women
were exposed. For the current analysis, we used only a crude job
classification; office worker or manual worker.
The odds ratio (OR) was used as a measure of association
between exposure to factors of interest and lung cancer. The OR
compares the odds of exposure of cases with that of controls.
Multivariate logistic regression methods were used to compute OR
and confidence intervals (CI) and to adjust for potential confound-
ing variables (Breslow and Day, 1980). The Maitel-extension test
was used to test for trend in the OR with exposure, using category
ranks as the quantitative trend variable (Mante2 and Haenszei,
1959). All trend tests were 2-sided.
*Correspondence to: Institute of Carcinogenesis, Kashirskoye shosse 24,
IvIoscow, Russia. Fax: 7-095-324-12-05. E-mail: maz L~epidem.msk.su
Received 18 June 1997; Revised 17 September J997
99035512

338 ZARIDZ.B FTALL
cancer in women whose husbands smoked filter cigarettes, either
for all histological types of lung cancer combined, or for squamous-
cell cancer or adenocarcinoma.
We identilied some potential methodological problems in our
study, concerning some aspects of design of the study, and in
particular the seleetion of controls. Although, in general, hospital-
based studies are more prone to selection bias than population-
based studies (Breslow and Day, 1980), they may offer less
opportunity to recall bias and therefore differential exposure
misclassification (1}edaniel et al., 1994).
Misclassification of the non-smoking status of cases and controls
(i.e., confounding by active smoking) is an important potential
source of bias in studies of the health effects of ETS (9}edaniel et
al., 1994). This problem is more likely to be present in studies
including both lifetime non-smokers and long-term quitters (Brown-
son et aL, 1992). The misclassification of smoking status is less
likely to he present among never-smokers, though both cases and
controls in our study could include a small fraction of light
smokers.
Misclassification of exposure to ETS is another important
potential source of bias (']tedaniel et al 1994). We have not used a
method of biochemical validation of ETS exposure, for example,
measurement of urinary cotinine. However, these methods could
only validate a recent history of exposure, which is clearly far less
important than Iong-term exposure to ETS.
Finally, differential misclassification of exposure (i.e., cases
over-reporting ETS exposure as compared with controls) is likely
to be less pronounced in our hospital-based study, since cases and
controls alike were patients and were interviewed in their hospital
wards.
Au important potential problem that may arise in studies on ETS
are potential confounders other than active smoking. We found no
evidence that occupational exposure or diet affects the risk of lung
cancer. However, in our smdy cases were less educated than
controls. In the statistical analyses, therefore, adjustments were
made for age and education. In addition, the results of our study
suggest the importance of different indices of air pollution as risk
determinants of lung cancer in non-smoking women. These results
will be reported elsewhere.
In conclusion, our study provides estimates of the effect of ETS
on lung-cancer risk in Russian non-smoking women who are
residents of Moscow. We found no increased risk for childhood
exposure, a result that is in line with most available data. There was
no association between exposure to ETS at the workplace and risk
of lung cancer. The risk of lung cancer from exposure to ETS from
the spouse was elevated. The use of several quantative indicators of
ETS exposure reinforced these conclusions- There was evidence of
a higher risk from ETS of cigarettes, without filter and "papirosy".
Detailed analyses showed a stronger association of ETS from
husbands' smoking with squamous-cell carcinoma.
ACKNOWII:UGEMENTS
The final statistical analysis was undertaken during D.M.'s
one-month visit to the IARC Unit of Environmental Cancer
Epidemiology, supported by UICC ICRETT fellowship 506.
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