a Graduate Institute of Medicine,
b School of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC 807.
c Massachusetts General Hospital Biostatistics Center, 50 Staniford Street, Boston, MA 02115, USA.
d Department of Internal Medical,
e Department of Surgery Medical,
f Department of Ophthalmology, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan, ROC 807.
Reprint requests to: Ying-Chin Ko, School of Public Health, Kaohsiung Medical University, No. 100 Shih-Chuan 1st Road, Kaohsiung, Taiwan, ROC 807. E-mail: ycko{at}mail.nsysu.edu.tw
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Abstract |
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Methods An age-matched case-control study was designed to investigate the effects of cumulative environmental exposure to tobacco smoke during childhood and adult life on lung cancer risk among non-smoking women in Taiwan. Information on passive smoking from all possible sources and life periods were obtained from interviews with 268 and 445 lifetime non-smoking cases and controls. Conditional logistic regression and synergism S index were applied to the data to assess the independent and joint effects of passive smoking in different life stages while controlling for possible confounding variables.
Results Risks of contracting lung cancer among women near-distantly exposed to the highest level of ETS in childhood (>20 smoker-years) and in adult life (>40 smoker-years) were 1.8-fold (95% CI : 1.22.9) and 2.2-fold (95% CI : 1.43.7) higher than that among women being never exposed to ETS, and the two variables accounted for about 37% of tumours in this non-smoking female population. Children were found to be more susceptible to ETS than adults and such early exposure was found to modify the effect of subsequent tobacco smoke exposure in adult life based on an additive interaction model.
Conclusions Environmental tobacco smoke exposure occurring in childhood potentiates the effect of high doses of exposure in adult life in determining the development of lung cancer. Smoking prohibition would be expected to protect about 37% of non-smoking Taiwanese women against lung cancer.
Keywords Lung cancer, environmental tobacco smoke, case-control studies, epidemiology, effect modification
Accepted 27 October 1999
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Introduction |
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Lung cancer has been the leading cause of cancer death for women in Taiwan since 1986. The cumulative mortality rate ranked as ninth highest in an international comparison of 18 countries or areas.5 According to annual cancer reports from the National Department of Health,6 there have been about 1350 female deaths from lung cancer per year in Taiwan in recent years (19911997). However, only 910% of women suffering from lung cancer had a history of cigarette smoking.7 The prevalence of smoking in females aged >16 years has remained at the low level of 25% for a long time (19741996), but the mortality trend over this period, in contrast, has increased steadily (Figure 1).8 Although cigarette smoking is considered to be the most important cause of lung cancer, it cannot fully explain the epidemiological characteristics of lung cancer in Taiwanese women, who smoke rarely but contract lung cancer relatively often. In Taiwan, annual nationwide surveys reported a high smoking prevalence (5562%) among men8 and, as expected, this has lead to a large amount of involuntary exposure of children and non-smoking women to ETS. Despite the fact that the authors in the previous study found that exposure to fumes emitted from cooking oils, when not reduced by an extractor such as a fume hood, appeared to be an important risk factor for lung cancer in non-smoking Taiwanese women,7,9 the role of ETS among female lung cancer patients should not be dismissed.
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Materials and Methods |
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The cases were drawn from Kaohsiung Medical University Hospital, which is a highly regarded teaching hospital in Southern Taiwan, and is accessible to patients from all socioeconomic groups. A system of rapid case recognition was introduced for the determination of lung cancer cases, so those patients could be recognized and selected into our study as soon after diagnosis as possible. In this system, all newly hospitalized women suspected of suffering from primary carcinoma of the lung (ICD-9, code 162) were traced from hospital medical records and quickly verified histologically by a pathologist. A total of 295 eligible cases of lifetime non-smoking women suffering from lung cancer were identified between January 1992 and June 1998. Of these, 14 patients had died or been discharged by the time the interviewers visited the wards, 7 were too ill to participate, and 6 refused to be interviewed. In all 268 (91%) non-smoking female lung cancer patients were interviewed.
The controls were derived from the same geographical areas as cases. They were also lifetime non-smoking women selected from hospitalized patients at the same hospital with conditions unrelated to tobacco use. The controls included patients with eye problems (cataract and glaucoma), bone fractures, and women undergoing physical check-ups. Identified by the same system of rapid disease recognition as the cases, the first and/or second eligible controls were selected within 3 weeks of the case being identified and matched to case on age (± 2 years). Only one control patient was matched to each of the first 78 cases during 1992 and 1993, due to administrative and budgetary limitations. All remaining cases were matched to two controls, except for 13 cases for each of whom, because of old age, only a single match could be found. Of the 492 non-smoking age-matched women identified as suitable controls, 445 (90%) agreed to be interviewed for the control group (eye problems: 52%; bone fracture: 27%; physical check-up: 21%).
Interviews
A structured questionnaire was completed for each case and control patient in a face-to-face interview by two trained interviewers. The questionnaire was designed to collect information on demographic characteristics, smoking history, lifetime occupations, dietary factors, history of lung diseases, cooking practices, cooking conditions, air pollution in general inside the home and ETS. A field supervisor checked all completed questionnaires and relevant medical records, which were then transferred to coding sheets for computer analysis.
Data specification
Lifetime smoking history of study subjects was collected through personal interview by the trained interviewers. Subjects' spouse or other next-of-skin were asked through a short interview for verification of their smoking status. People who did not smoke as much as one cigarette per day for one year, or >365 cigarettes over their lifetime were considered lifetime non-smokers. Information about cases and controls exposed to ETS was collected for three categories. These included childhood (18 years) exposure at home, adult life (
19 years) exposure at home and workplace exposure. In each time period at home, any patient living with a regular family member who was a smoker for at least one year was considered to be a potential passive smoker. Among these, a passive smoker was identified as a patient whose family members had smoked in her presence, as some Chinese smokers do not smoke at home in the presence of their family. After establishing passive smoker status, a series of detailed questions was asked for each active smoker identified about such circumstances as: duration, starting year, stopping year and the number of years living with the smoker. For patients who had a regular job, the exposure was measured by asking patients whether they were exposed to tobacco smoke generated by co-workers in the workplace. Each job held for
5 years was assessed separately. Patients who reported being passive smokers were also asked to indicate the number of years the co-worker smoked in their presence and the number of active smokers in the workplace. Three indicators of tobacco smoke exposure were constructed for these three categories of exposure: (1) a dichotomous variable which classified patients as those who reported any exposure versus none; (2) total number of smokers; (3) total number of smoker-years, calculated by summing the number of years the passive smokers reported exposure to each active smoker. Among these indicators, exposure sources in childhood at home included father, mother and other family member, and in adult life at home, included husband, husband's father and other family members. Otherwise, pack-years of exposure to husband's smoking were estimated by multiplying the number of packs of cigarettes smoked per day in the subject's presence by the number of years he smoked while living with her.
Information on other air pollution factors inside the house, such as Chinese incense, mosquito coils and cooking fuels were also collected. Questions were directed at the type of material used, duration and frequency of burning and the age of patient at the time of exposure. Each housewife who had to cook for her family was asked about cooking habits frequently used and the type of exhaust ventilation systems employed in kitchens such as chimneys or fume extractors. Other questions were directed at factors such as lifetime occupation, daily diet, and history of lung disease. Occupations were classified into one of five categories: administration, hazardous industry, farmer, housewife and others, and a person's lifetime occupation was taken to be the job they held the longest. Daily dietary habits were assessed by measuring the frequency and quality of consumption of 12 food items, including meat, vegetables, fruits, pickles, smoked food, etc. Information on lung diseases including tuberculosis, emphysema, chronic bronchitis and asthma were separately collected.
Statistical analysis
We analysed the collected data using the statistical software package STATA.10 Analyses included the 2 test for comparing demographic factors and some multivariate techniques specially designed for matched case-control studies. To explore the distribution of risk factors, tables of case and control numbers were studied rather than matched pairs. Odds ratios (OR) and 95% CI for various associations were determined from matched pairs using conditional logistic regression models.11 Statistical significance of trends for matched pairs were calculated by categorizing exposure variables and treating scored variables as continuous. All OR estimates were adjusted for residential area, educational level and occupation, in order to reduce residual confounding, as well as for tuberculosis, cooking fuels and fume extractor, which were found to confound the association between passive smoking and lung cancer in this study. Interactive effects of exposure to ETS during childhood and adult life (including exposure at home and workplace) were evaluated by assuming an additive or a multiplicative interaction relationship. Main effect variables for the two exposure periods and their cross-product terms were incorporated into the logistic regression models for the testing of interaction based on a multiplicative model. The synergism S index proposed by Rothman and its 95% CI were computed to evaluate the empirical deviation from the additive interaction relationship.12 Otherwise, the proportion of lung cancer cases attributable to tobacco smoke exposure generated in different life stages (population attributable risks proportion) was calculated according to Buzzi et al.'s method.13
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Results |
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Discussion |
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In the exploration of the cause-effect relationship and risk assessments between environmental exposure to tobacco smoke and lung cancer, the most commonly reported index of passive smoking in earlier epidemiological studies has been the presence or absence of a smoking spouse.16,17 This type of exposure index has been frequently queried and found to be inaccurate,4,18 because of the lack of consideration of passive smoke exposure which may occur outside the household, as well as that which may have occurred during childhood. Cummings et al.19 have tried to measure the association between ETS exposure occurring during childhood, adult home exposure and workplace exposure. Unfortunately, little association was found, and reliance on measurement during a single life stage (e.g. adult life) or from a single source (e.g. spouse) to define lifetime exposure, probably results in the misclassification of a substantial number of subjects. On the other hand, the adverse health effects associated with passive smoking have been found to be different between exposures in different life stages. Janerich et al.20 and Wang et al.4 in their case-control studies indicated that exposure to passive smoking during childhood may predispose a person to develop lung cancer later in life, regardless of adult exposure. Evidence from these studies suggests that the effect of passive smoking on lung cancer should be assessed on the basis of exposure from different life stages.
No appropriate gold standard, not even urine cotinine level, is available to verify the validity of questionnaire measures of lifetime involuntary smoking. However, questionnaire responses with good reliability are believed more likely to have good validity. Coultas et al.21 and Brownson et al.22 compared responses on smoking behaviours of each household member between original and second interviews conducted within several months of follow-up. Concordance was high (>84%) both for parental smoking status during childhood and for spouses smoking status during adult life, although the agreement for ETS exposure measured by quantitative methods were not as high. Methodological study concerned with the reliability of various exposure sources between subjects' passive smoking reports and exposure reports by those of surrogates also showed that agreement of exposure generated by parents or spouse was relatively high compared to that generated by other household members or co-workers.19 For studies of the health effects of lifetime passive smoking, for which parents and spouse were considered separately as the major exposure sources during childhood and adult life, high reliability on the relevant responses could reduce the probability of exposure misclassification in different life stages.
In this study, all possible sources of tobacco smoke exposure were assessed from childhood and throughout adult life. The authors employed an index of passive exposure, which embodies both the numbers of active smokers as well as the years smoked by each smoker to assess the effect of exposure accumulated in various life stages. The exposure index used concurrently verified that the subjects with a smoking relative or co-worker were in fact exposed to passive smoke (e.g. that the active smoker smoked in their presence), as not all subjects are substantially exposed to passive smoke when living with an active smoker. This is an important valid qualification of environmental exposure to tobacco smoke. In fact, if we carried out our data analysis on the basis of binary yes or no categories for the smoking family member or co-workers, most of our positive findings concerning the relationship between passive smoking and lung cancer weakened or vanished. This type of misclassification of ETS exposure may partly account for the lack of significant positive findings in previous studies.
The relationship between involuntary exposure to tobacco smoke in different life stages and lung cancer has been increasingly noticed in recent studies.4,20,2226 Risk assessment studies concerned with exposure during adult life have consistently found that a smoking husband significantly elevated the risk of lung cancer at the highest level of exposure,2225 a finding consistent with this study. In contrast, the risk pattern of contracting lung cancer is not so compatible for exposure occurring during childhood. Brownson et al.22 and Fontham et al.,24 in studies with large sample sizes, found no excess risk of lung cancer from parents' smoking, even though cumulative household exposure up to the level of >18 smoker-years was examined. However, Janerich et al.20 and Stockwell et al.,23 as in our study, identified an about twofold risk of lung cancer when the subject had 20 smoker-years of household exposure during childhood. Wang et al.4 found a 3.1-fold increased risk of lung cancer associated with tobacco smoke exposure before the age of 23 years. Because an exposure of 20 smoker-years is equivalent to living with one smoker during the first two decades of life, a high but not uncommon level of exposure,20 even if the differences in findings among the studies can not be reconciled, the impact of childhood exposure in enhancing the risk of lung cancer in adult life should not be dismissed.
Our non-smoking women exposed to various levels of ETS in their childhood were found to contract lung cancer in proportion to their exposure, with significantly elevated risks (2.2-fold) at the highest level (>20 smoker-years). In contrast, significantly elevated risks (2.6-fold) in adult life were registered at exposure levels >40 smoker-years, but not between 2140 smoker-years, although as exposure increased so did the risks. Similar relationships between passive smoking in childhood and incidence of lung cancer were observed by studies conducted in New York20 and Florida,23 and the existence of a threshold for childhood exposure to tobacco smoke was suggested. Otherwise, the exposure level which results in significant elevated risk may be easier to reach in childhood than in adult life. The increased risk associated with a one-unit increase in smoker-years was somewhat larger for childhood exposure than for exposure during adult life (OR = 1.35 for childhood; OR = 1.27 for adult life), when smoker-years was treated as a continuous variable and risk estimates were adjusted for exposure in the other life stages. Because of imperfect metabolism, detoxification and immunity in children,4 susceptibility to ETS in this non-smoking female population may be greater in childhood than in adulthood. It is interesting that children exposed to household tobacco smoke are not only more susceptible to various respiratory syndromes,1 but also to lung cancer later in adult life. In addition, it has been proposed that women with a history of non-malignant lung disease are exposed to an increased risk of lung cancer.17,18 According to Janerich et al.,20 childhood respiratory diseases may initiate certain changes, which may lead to lung cancer later in adult life.
Our findings indicated that there was insufficient statistical evidence to explain the difference between observed and expected OR for the joint effects of passive smoke in childhood and adult life based on the multiplicative interaction relationship. However, the synergism S index indicated that the interaction structure between exposures in these two life stages started to deviate significantly from the additive model at exposure levels >40 smoker-years. Although only about 3233% of lifetime exposure to ETS occurred in childhood, this, based on an additive interaction model, appeared to modify the risk effect of subsequent tobacco smoke exposure during adult life. Otherwise, the appearance of a 2.6-fold of relative excess risk in the combined exposure of two life periods at the highest exposure level (>40 smoker-years), as well as 3.3-fold increase in risk observed from a population-based case-control study for non-smoking women who were exposed to both childhood household smoke and had the highest level of adult exposure (>48 smoker-years),24 may suggest that ETS exposure occurring early in life potentiates the effect of high doses of exposure in adult life in determining the development of lung cancer.
There was a lower proportion of workplace exposure to tobacco smoke in this study (6.710.2%) than that reported by Kabat et al.17 and Fontham et al.24 (57.063.2%). This is not surprising since, for women, a large proportion of their occupation categories did not give them any chance of exposure to ETS (housewife; 2729%), or made it easy for them to escape the exposure (farmers; 2629%). Exposure in the household has been incorporated in household exposure in adult life (others category; 1415%, mostly women who work in their home). In fact, the number of active smokers and years exposed were examined for women who reported workplace exposure; the mean value of 2.5 smokers and 11.3 exposed years respectively was found in our control group, which is not far from such exposure observed by other studies.19
In a female population, such as Taiwanese women, who smoke relatively rarely, but live in an environment with high male smoking prevalence, the population burden of lung cancer due to ETS is relatively important. In our present study, about 18.4% and 25.5% of the aetiologic fraction of lung cancer were separately attributed to environmental exposure to tobacco smoke during childhood and adult life. Tobacco use by the children's father (58.5%) and wife's husband (72.9%) were found to account for the majority of exposure in a respondent's childhood and adult life, respectively. Otherwise, a 37.2% population attributable risk proportion due to lifetime exposure to passive smoke was detected, and therefore it is reasonable to expect that prohibition of smoking at home or in public places could yield considerable health benefits, for both children or non-smoking women in Taiwan.
In summary, environmental exposure to tobacco smoke in childhood and adult life both contributed independently to the risk of contracting lung cancer. Children were found to be more susceptible to ETS than adults and such early exposure appeared to modify the effect of subsequent tobacco smoke exposure in adult life. Smoking prohibition would be expected to protect about 37% of non-smoking Taiwanese women against lung cancer.
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Acknowledgments |
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References |
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