This study analyzed data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). The NHIS-NSC is a population-based cohort established by the National Health Insurance Service (NHIS) in South Korea . The NHIS is a single-payer health insurance system in South Korea that covers the entire South Korean population (approximately 48 million in 2003). The NHIS provides biennial health screening to all insured adults aged 40 years or older. The NHIS-NCS database consists of 514,795 participants who were aged between 40 and 79 in 2002 and underwent health screening programs in 2002 or 2003; 2002 for participants born in an even year and 2003 for participants born in an odd year (Figure 1).
After excluding 16,757 patients (12,063 never smokers, 1,685 former smokers, and 3,009 smokers) with previous histories of cancer diagnoses before January 1, 2004, classified by the International Classification of Diseases 10th revision (ICD-10) codes for cancer diagnoses or questionnaires on previous medical history, 321,342 never-smokers, 42,444 former smokers, and 115,304 smokers were included in the final study cohort (Figure 1). Finally, the cohort consisted of six arms, never-smokers without COPD (N = 313,553), former smokers without COPD (N = 41,359), smokers without COPD (N = 112,627), never-smokers with COPD (N = 7,789), former smokers with COPD (N = 1,085), and smokers with COPD (N = 2,677) (Figure 1). We investigated the development of new cancers, including lung cancer, stomach cancer, colorectal cancer, liver cancer, acute myeloid leukemia (AML), esophageal cancer, bladder cancer, and kidney cancer from January 1, 2004, to December 31, 2015, a 12-year period (Figure 1-2).
Definition and covariates
COPD was identified by the combination of ICD-10 codes J43-J44 for COPD (simple and mucopurulent chronic bronchitis, unspecified chronic bronchitis, emphysema, and other chronic obstructive pulmonary diseases) and use of the following medications for COPD (≥ 4 times in two years) : long-acting muscarinic antagonists (LAMA), long-acting beta-2 agonists (LABA), LAMA + LABA , inhaled corticosteroids (ICS) + LABA, triple therapy (LAMA + LABA + ICS), short-acting muscarinic antagonists (SAMA), short-acting beta-2 agonists (SABA), phosphodiesterase-4 (PDE-4) inhibitors, mucolytics, or theophylline [15, 16].
Detailed history of smoking (smoking amount, duration, and non-smoking period), exercise status (intensity and frequency per week) were evaluated by self-administered questionnaires at baseline in 2002 or 2003. Former smokers were defined as smokers whose smoking cessation period was one year or more at enrollment . Data on body mass index (body weight in kilograms divided by height in meters squared ; kg/m2), systolic and diastolic blood pressure, fasting serum glucose, and fasting total cholesterol level measured at baseline were obtained.
Main outcome measures
The primary outcome was the incidence of lung cancer. The secondary outcomes were the incidence of stomach cancer, colorectal cancer, liver cancer, AML, esophageal cancer, bladder cancer, and kidney cancer.
The outcome measures were ascertained by health insurance claims data in the NHIS from January 1, 2004, to December 31, 2015. The first incident event was only used in the analyses for participants with more than one event. ICD-10 codes were used to identify outcome measures as follows: lung cancer (C33, C34), stomach cancer (C16), colorectal cancer (C18, C19, C20), liver cancer (C22), AML (C92.0), esophageal cancer (C15), bladder cancer (C67), and kidney cancer (C64 - C66).
All values were expressed as mean ± standard deviation. Continuous and categorical variables were analyzed with one-way analyses of variance (ANOVA) and chi-square tests, respectively. Univariate Cox proportional hazards regression analyses were used to identify significant variables predicting the occurrence of an event individually (p < 0.01). Then, multivariable Cox proportional hazard models were performed to evaluate the independent effects of COPD on the development of cancer, adjusting for age, gender, hypertension, diabetes, body mass index, and exercise variables. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for the risk of lung cancer, stomach cancer, colorectal cancer, liver cancer, AML, esophageal cancer, bladder cancer, and kidney cancer.
A conservative threshold of P < 0.01 was determined to be significant, considering a large sample size of this study. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC, USA)
The present study was approved by the Institutional Review Board of Ajou University Hospital (No. AJIRB-MED-EXP-17-167).