Tobacco smoking and risks of more than 470 diseases in China: a prospective cohort study

Abstract

Background: Tobacco smoking is estimated to account for more than 1 million annual deaths in China, and the epidemic continues to increase in men. Large nationwide prospective studies linked to different health records can help to periodically assess disease burden attributed to smoking. We aimed to examine associations of smoking with incidence of and mortality from an extensive range of diseases in China.

Methods: We analysed data from the prospective China Kadoorie Biobank, which recruited 512 726 adults aged 30-79 years, of whom 210 201 were men and 302 525 were women. Participants who had no major disabilities were identified through local residential records in 100-150 administrative units, which were randomly selected by use of multistage cluster sampling, from each of the ten diverse study areas of China. They were invited and recruited between June 25, 2004, and July 15, 2008. Upon study entry, trained health workers administered a questionnaire assessing detailed smoking behaviours and other key characteristics (eg, sociodemographics, lifestyle, and medical history). Participants were followed up via electronic record linkages to death and disease registries and health insurance databases, from baseline to Jan 1, 2018. During a median 11-year follow-up (IQR 10-12), 285 542 (55·7%) participants were ever hospitalised, 48 869 (9·5%) died, and 5252 (1·0%) were lost to follow-up during the age-at-risk of 35-84 years. Cox regression yielded hazard ratios (HRs) associating smoking with disease incidence and mortality, adjusting for multiple testing.

Findings: At baseline, 74·3% of men and 3·2% of women (overall 32·4%) ever smoked regularly. During follow-up, 1 137 603 International Classification of Diseases, 10th revision (ICD-10)-coded incident events occurred, involving 476 distinct conditions and 85 causes of death, each with at least 100 cases. Compared with never-regular smokers, ever-regular smokers had significantly higher risks for nine of 18 ICD-10 chapters examined at age-at-risk of 35-84 years. For individual conditions, smokers had significantly higher risks of 56 diseases (50 for men and 24 for women) and 22 causes of death (17 for men and nine for women). Among men, ever-regular smokers had an HR of 1·09 (95% CI 1·08-1·11) for any disease incidence when compared with never-regular smokers, and significantly more episodes and longer duration of hospitalisation, particularly those due to cancer and respiratory diseases. For overall mortality, the HRs were greater in men from urban areas than in men from rural areas (1·50 [1·42-1·58] vs 1·25 [1·20-1·30]). Among men from urban areas who began smoking at younger than 18 years, the HRs were 2·06 (1·89-2·24) for overall mortality and 1·32 (1·27-1·37) for any disease incidence. In this population, 19·6% of male (24·3% of men residing in urban settings and 16·2% of men residing in rural settings) and 2·8% of female deaths were attributed to ever-regular smoking.

Interpretation: Among Chinese adults, smoking was associated with higher risks of morbidity and mortality from a wide range of diseases. Among men, the future smoking-attributed disease burden will increase further, highlighting a pressing need for reducing consumption through widespread cessation and uptake prevention.

Funding: British Heart Foundation, Cancer Research UK, Chinese Ministry of Science and Technology, Kadoorie Charitable Foundation, UK Medical Research Council, National Natural Science Foundation of China, Wellcome Trust.

Figure 1. Adjusted HRs for cause-specific disease incidence significantly associated with ever-regular smoking

Hazard ratios (HRs) were stratified by age-at-risk (5-year groups), sex, and study area and were adjusted for education and alcohol drinking. All analyse were restricted to age-at-risk range of 35-84 years. The solid boxes represent HRs, with the size inversely proportional to the variance of the logarithm of the HR, and the horizontal lines represent 95% confidence intervals. The individual diseases listed included all that showed FDR-adjusted significant associations with smoking, in overall or sex-specific analyses. The solid black and grey boxes indicate FDR-adjusted significant and non-significant associations, respectively.

Figure 2. Adjusted HRs for risks of selected major disease incidence and mortality in urban and rural men who started smoking before 20 years old

Convention as in Figure 1.

Figure 3. Incidence and mortality rates from all diseases found to have a FDR-adjusted significant association with ever-regular smoking

The bar diagrams indicate the overall absolute morbidity and mortality rates per 100,000 person-years at age-at-risk 35-84 years in never- versus ever-regular smokers, overall and in men and women separately. Within each bar diagram, separate rates were also shown for circulatory (black), respiratory (grey) and other diseases (white). The morbidity analyses included 56 diseases showing positive associations with smoking and seven showing inverse associations. The mortality analyses were based on the 22 causes of death showing significant positive associations with smoking.