Association of transitioning from combustible cigarettes to noncombustible nicotine or tobacco products with subsequent cancer risk: a nationwide cohort study in South Korea

1. Introduction

While the prevalence of Combustible cigarette (CC) smoking has declined in many high-income countries over recent decades, the use of noncombustible nicotine or tobacco products (NNTP) has risen due to its promotion as a helpful aid for adults looking to quit CC smoking.[1, 2] Although evaluations of the components of various NNTPs have revealed the presence of various well-known carcinogenic agents, there has been limited research examining their carcinogenic effects, such as cancer development.[3] Thus, this study aimed to assess the association of changes in NNTP and CC use habits and subsequent overall cancer risk.

2. Methods

This study utilized data from the National Health Insurance Service of South Korea (NHIS), which includes demographics, socioeconomic status, and medical data for the diagnosis and treatment modalities of participants who underwent complimentary national health checkups biannually.[4] The study population consisted of 5,312,023 adults aged 20 years and older who underwent health checkups during both the first period (2014) and second period (2018). Starting from the second health screening date, participants were followed up until the date of the overall cancer event or death, whichever came earliest.

Smoking status was assessed through a self-reported survey during the first and second health check-up periods.[2] NNTP use was evaluated through a survey during the second health check-up period. CC quitters were classified into long-term (≥5 years) and recent (<5 years) quitters, as it is considered to take 5 years for CC quitters to gradually decrease overall cancer risk.[2] Similar to a previous study[2], the participants were classified into six groups: continual CC-only smokers, CC and NNTP users, recent (<5 years) CC quitters, long-term (≥5 years) CC quitters without NNTP use, long-term (≥5 years) CC quitters with NNTP use, and never smokers. In this study, all cancer cases were identified using the International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes, specifically C00-C99.[5]

Multivariate Cox proportional hazards regression was used to calculate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for overall cancer based on changes in CC and NNTP use status. Stratified analysis of the association between smoking status and overall cancer risk was performed across age and sex subgroups, adjusting for all covariates except for the variable used to stratify the subgroups. Statistical significance was determined at a 2-sided P-value of less than 0.05. All data collection and statistical analyses were performed using the SAS software (version 9.4; SAS Inc., Cary, NC, USA).

3. Result

Among 4,187,557 participants (Table 1), The risk of overall cancer according to changes in CC and NNTP usage habits according to age and sex is presented in Table 2. Compared with continual CC-only smokers, CC and NNTP users (aHR, 0.86 [95% CI, 0.79–0.93]), recent CC quitters (0.92 [0.87–0.97]), long-term CC quitters without NNTP use (0.74 [0.71–0.77]), and never smokers (0.61 [0.59–0.63]) had lower risk for overall cancer in male participants aged 40 years or older. Additionally, compared with continual CC-only smokers, CC and NNTP users, recent CC quitters, long-term CC quitters without NNTP use, long-term CC quitters with NNTP use, and never smokers exhibited lower trends of overall cancer risk in female participants aged 40 years or older. However, there were significant differences in the association between changes in CC and NNTP use habits and overall cancer risk across the different age subgroups (Table 2).

4. Discussion

In summary, switching to NNTP among initially CC-only smokers was associated with a lower overall cancer risk than continual CC-only use in participants aged 40 years or older. There is a trend of decreasing cancer incidence in women aged 40 years or older, but this was difficult to determine owing to the insufficient sample size. To the best of our knowledge, this is the first study to demonstrate the overall cancer risk associated with changes in NNTP and CC habits.

Several limitations must be considered when interpreting the results. First, because 97% of all women in South Korea are nonsmokers, there may be a discrepancy between smoking status, as reported in surveys, and the actual smoking status. Additional follow-up will enhance the reliability of the results obtained in this cohort.