Smoking and lung cancer in Harbin, northeast China

J. Hu1,2, C. Galeone3,*, R. Lui2, C. Pelucchi3, C. La Vecchia3,4 and E. Negri3

1 Surveillance and Risk Assessment Division, Centre for Chronic Disease Prevention and Control, Public Health Agency of Canada, Ottawa, Ontario, Canada; 2 Department of Epidemiology, Harbin Medical University, Harbin, China; 3 Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan; 4 Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy

* Correspondence to: Dr C. Galeone, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via Eritrea 62, 20157 Milan, Italy. Tel: +39-02-39014577; Fax: +39-02-33200231; E-mail: galeone{at}marionegri.it


    Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background: We studied the relationship between smoking and lung cancer risk in Harbin, Heilongjiang province, northeast China, an area with a very high baseline risk of lung cancer in both sexes, using data from a case–control study of lung cancer conducted between 1987 and 1990.

Patients and methods: Cases were 218 patients with incident, histologically confirmed lung cancer and controls were 436 patients admitted to the same hospital with non-neoplastic and non-lung diseases.

Results: Compared with never-smokers, the multivariate odds ratio (OR) for current smokers was 3.47 [95% confidence interval (CI) 2.31–5.20], and for ex-smokers 1.53 (95% CI 0.81–2.87). Lung cancer risk increased by 20% (95% CI 14% to 28%) for an increment of 5 years in smoking duration, and by 29% (95% CI 15% to 45%) for an increment of five cigarettes per day. The OR for smokers reporting occupational exposure to selected known or likely lung carcinogens was 7.22, compared with non-smokers without occupational exposure.

Conclusions: This study further confirms that cigarette smoking is a strong determinant of lung cancer also in this high-risk area of northeast China.

Key words: case–control, China, lung cancer, smoking habit


    Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
In studies from Western countries, cigarette smoking is responsible for up to 90% of male cases [1Go, 2Go] and the risk of lung cancer in smokers is ~10 times that for non-smokers. For example, mortality in heavy cigarette smokers was 15 times that of non-smokers in a cohort of British male doctors [3Go], and in the American Cancer Society Cancer Prevention Study (CPS-I) the lung cancer mortality rate ratios in long-term smokers were >10 for men and >5 for women [4Go]. Conversely, in several Chinese studies, the risks in smokers are two to three times higher than those in non-smokers [5Go]. A combined analysis of 15 Chinese case–control studies of lung cancer found a summary odds ratio (OR) of 2.2 for ever-smokers, and population-attributable risks (PARs) of 57% for males and 33% for females [6Go, 7Go]. A retrospective proportional mortality study found that, for both sexes, lung cancer death rates at age 35–69 years were about three times greater in smokers than in non-smokers. However, since the rates among non-smokers in different parts of China varied widely, the absolute excesses of lung cancer in smokers also varied [8Go].

These differences with Western countries may be ascribed to the particular patterns of tobacco consumption (large use of pipe and cigars) [9Go], as well as to the low average daily tobacco consumption [10Go, 11Go] in China before 1980.

The northeastern Chinese areas of Harbin, Jilinshi and Shenyang had very high lung cancer death rates in both smokers and non-smokers in a retrospective mortality study including ~1 million deaths, conducted in 98 areas of China [8Go, 12Go]. In particular, Harbin had the highest death rates for female smokers (about 3 per 1000) and non-smokers (0.9 per 1000) at ages 35–69 years. This has been attributed to the high indoor pollution related to fumes from domestic heating and cooking [13Go–15Go]. As a comparison, in other Chinese areas and in the USA the corresponding rate for non-smoking women was ~0.1 per 1000 [8Go, 16Go]. In spite of the high rates in non-smokers, in Harbin the risk ratio of lung cancer for smokers was 2.58, similar to the rest of China [8Go]. A large case–control study of female lung cancer conducted in Shenyang and Harbin found a 2.3-fold increased risk for smokers, with significant trends for number of cigarettes and duration of smoking [17Go]. In a previous investigation conducted on a population from the same area, the OR for ≥25 cigarettes per day was 3.7 for men [18Go].

In this paper we further assess the relationship between tobacco smoking and lung cancer using data from a case–control study conducted in Harbin.


    Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The study was conducted between May 1987 and May 1990 in Harbin, Heilongjiang province, northeast China. Both cases and controls had to be resident in Heilongjiang province. In the study province, the 218 newly diagnosed, histologically confirmed lung cancer cases were hospitalized in the Department of Cardiothoracic Surgery of the Hospitals in this area. The controls were patients hospitalized in the Department of General Surgery, Cardiothoracic Surgery, Urological Surgery and Orthopaedic Surgery for non-neoplastic and non-lung diseases at the hospital where the cases were recruited. For each case, two controls were individually matched by sex, 5-year age interval and area of residence. For cases residing in the city of Harbin, controls from Harbin were used. For cases from rural areas or small towns, controls were matched to subjects living in the same or adjacent place (town or rural). Diagnoses at admission of controls comprised: conditions requiring general surgery, 183 (42%); urological diseases, 126 (28.9%); and orthopaedic diseases and trauma, 127 (29.1%). Before surgery, the study subjects were interviewed in the hospital wards by two interviewers especially trained using a structured questionnaire. Information was collected on socioeconomic status, medical history of lung diseases, smoking history, histories of occupation and exposure to recognized lung carcinogens [19Go], residential histories, and types of heating and cooking fuels use at home.

A smoker was considered as anyone who smoked at least one cigarette per day for 1 year or more. The questionnaire also collected information on the lifetime exposure to environmental tobacco smoke by source (i.e. home or workplace), intensity (i.e. number of smokers) and duration of exposure. Size in square meters of the home or workplace was also recorded.

Data analysis
ORs and 95% confidence intervals (CIs) were computed as measures of the relative risk using unconditional logistic regression models. Adjustments were made for sex, age, education, family history of lung cancer, residence (urban or rural), and exposure to coal and to recognized lung carcinogens.


    Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Table 1 gives the distribution of cases and controls according to age, sex, education, family history of lung and other cancers, and occupational exposure to recognized lung carcinogens. Lung cancer cases had a similar age and education distribution to controls. Cases more frequently reported a family history of lung cancer (OR 2.12; 95% CI 0.93–4.86) and of other cancers (OR 1.53; 95% CI 0.86–2.76) than controls, and an occupational exposure to recognized lung carcinogens (OR 1.79; 95% CI 1.18–2.71).


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Table 1. Distribution of 218 cases of lung cancer and 436 controls according to age and selected characteristics: Harbin, China, 1987–1990

 
Table 2 gives the distribution of lung cancer cases and controls according to selected smoking related variables, and the corresponding OR compared with never-smokers. Cases were more frequently current smokers (62.8%) than controls (38.3%), and the corresponding OR was 3.47 (95% CI 2.31–5.20). Ex-smokers had an OR of lung cancer of 1.53 (95% CI 0.81–2.87). In current smokers, the OR was 4.29 (95% CI 2.59–7.01) for smoking duration ≥35 years, and lung cancer risk increased by 20% (95% CI 14% to 28%) for an increment of 5 years in duration. On average, cases smoked much more cigarettes per day than controls. The OR was 3.66 (95% CI 2.10–6.40) in smokers of ≥15 cigarettes per day, and lung cancer risk increased by 29% (95% CI 15% to 45%) for an increment of five cigarettes per day. All tests for linear trend were significant (P <0.01). Taking as the reference category smokers of factory-made cigarettes, and also adjusting for duration and amount of smoking, the ORs were 1.98 for smokers of hand-made cigarettes and 2.07 for smokers of both types.


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Table 2. ORs and 95% CIs of lung cancer according to smoking habit: Harbin, China, 1987–1990

 
Table 3 shows the ORs according to the smoking habits in strata of sex, area of residence, education and occupational exposure to recognized lung carcinogens. No appreciable or significant heterogeneity emerged across various strata considered. P values for interaction tests were 0.21 for sex, 0.77 for area of residence, 0.15 for education and 0.37 for occupational exposure to recognized lung carcinogens.


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Table 3. ORs and 95% CIs of lung cancer according to smoking habit, in separate strata of selected covariates: Harbin, China, 1987–1990

 
The combined effect of smoking and occupational exposure to lung carcinogens is shown in Table 4. Compared with subjects not exposed to smoking and occupational lung carcinogens, the OR was 7.22 for those reporting both exposures.


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Table 4. ORs and 95% CIs of lung cancer according to combined exposures to smoking and recognized lung carcinogens: Harbin, China, 1987–1990

 

    Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
This study further quantifies the association between cigarette smoking and lung cancer risk in a high lung cancer risk area in northern China. Compared with never-smokers, the OR for current smokers was 3.5, and increased with duration and dose.

In this and other studies in the same population [18Go, 20Go], hand-made cigarettes were associated with a higher lung cancer risk than factory-made ones, even after adjustment for smoking quantity. The major difference between factory-made and hand-made cigarettes in Heilongjiang is that hand-made cigarettes use dry tobacco leaves without any processing. Cigarettes manufactured in China were once thought to be less harmful, but subsequent studies indicated that risks of lung cancer among Chinese smokers are comparable to those in Western societies once the amounts smoked are standardized [21Go]. Investigation in areas of China with exceptionally high rates of lung cancer provide some of the strongest evidence to date that indoor air pollutants may increase cancer risk [22Go]. In urban Shenyang and Harbin, indoor pollution from use of ‘kang’ and other coal-burning heating devices contributes to the area's high rates of lung cancer [14Go, 17Go]. This, in combination with the lower dose of cigarettes [in fact in this study only a small portion of controls (11%) smoked more than 15 cigarettes per day], may at least partially explain the lower PAR for smoking, which in this study was 48% (adjusted for major confounding factors), as compared with Europe and North America. Other studies from the same area found PAR to vary between 26% and 52% [9Go]. In this study, the PAR was 59% for males and 18% for females, whereas in industrialized countries the lung cancer mortality attributable to smoking in the year 2000 was >90% for males and 70% for females [7Go, 23Go].

When we examined the combined effect of smoking and selected occupational exposures, the two factors appeared to act independently on lung cancer risk, although the data were too scanty to further model their joint effect. In addition, stratified analysis found no heterogeneity across any covariate of interest. This study, however, was of relatively limited size, which hampered any analysis of subgroups or interactions.

Among potential sources of bias, the study was not population-based and did not record information on histological type of lung cancer. On the other hand, participation in the study was practically complete, cases and controls came from similar catchment areas, and allowance for major identified potential confounding factors did not modify any of the results.

In conclusion, this study further confirms that cigarette smoking is a strong determinant of lung cancer also in this high risk area of northeast China, that the lower risks observed in China for ever-smokers are due to a lower amount of cigarettes consumed and that hand-made cigarettes lead to a higher risk of lung cancer than factory-made ones.


    Acknowledgements
 
The authors wish to thank Mrs Ivana Garimoldi for her editorial assistance. This work was conducted with the contribution of the Italian Association for Cancer Research and the Italian League against Cancer.

Received for publication March 24, 2005. Revision received May 4, 2005. Accepted for publication May 24, 2005.


    References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
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