The Korean Cancer Prevention Study (KCPS) is a prospective cohort study designed to assess cancer risk factors by examining disease incidence, mortality, and hospital admissions. The KCPS cohort is primarily composed of government employees, teachers, and their dependents insured by the Korean Medical Insurance Corporation from 1992 through 1995. Subjects had at least one medical examination and completed a questionnaire during that period. The KCPS cohort includes 1,329,525 Koreans (846,907 men and 482,618 women) from 30 to 95 years of age who met the above selection criteria. This study did not include insured workers in its retrospective analysis because the WBC count of these individuals was not recorded during their medical examination. Therefore, the current analysis was limited to insured workers' family dependents in 1993 and 1995 (n=448,978). Then, 11,332 subjects whose WBC counts were less than 3,000 cells/mm³ or more than 11,000 cells/mm³ were also excluded from this analysis. To avoid confounding the association among smoking, BMI, and WBC count, 13,448 subjects who reported a history of cancer, CVD, respiratory disease, renal disease, and liver disease were also excluded. Additionally, 9,146 subjects with missing data on any covariate information or who had an extremely low BMI (<16.0 kg/m²) or short stature (<130 cm) were excluded from the study. After these exclusions, 416,065 participants (105,505 men and 309,560 women) between the ages of 30 and 95 years were included in the final analyses.

Medical examinations were performed according to a standardized procedure and were conducted by medical staff at local hospitals. In the 1993 and 1995 questionnaires, participants were asked about their smoking habits and other health-related behaviors. Body weight and height were measured with participants wearing light clothing without shoes to the nearest 0.1 kg and 0.1 cm, respectively. Participants were also asked if they were currently being treated for cancer or other diseases. If so, they were asked for the date of diagnosis. The completed questionnaires were reviewed by trained staff and then entered into a database. WBC count and serum levels of glucose and total cholesterol were measured under fasting conditions for routine clinical purposes. Each hospital had internal and external quality control procedures directed by the Korean Association of Laboratory Quality Control. Smoking exposure was categorized according to smoking status (non-smokers, ex-smokers, and current smokers) and the number of cigarettes per day among current smokers (1 to 9, 10 to 19, and 20 or more). BMI (kg/m²) was calculated as the ratio of weight (kg) and height (m²), and was divided into seven categories: <18.5, 18.5–19.9, 20.0–21.4, 21.5–22.9, 23.0–24.9, 25.0–26.9, and ≥27.0 kg/m². The total daily alcohol consumption was expressed as the number of glasses per week in relation to Korea's most popular alcoholic beverage, ‘soju.’ One glass of soju contains about 12 g of ethanol. Alcohol consumption per day was categorized as follows: none (0 g), light (1–14.9 g), and moderate to heavy (15 g or more). Participants were also asked to report if they exercised regularly. WBC counts were quantified using automated blood cell counters (Beckman Coulter, Fullerton, CA, USA) in hospital laboratories. Fasting serum glucose and total cholesterol levels were analyzed using enzymatic methods with an automatic chemistry analyzer (Hitachi 7600-110; Hitachi, Tokyo, Japan). Impaired fasting glucose was defined as ≥100 fasting plasma glucose level <126 mg/dL. Diabetes was defined from self-reported history or when the fasting serum glucose level was ≥126 mg/dL. Pre-hypertension was defined as a systolic pressure of 120–139 mm Hg or a diastolic pressure of 80–89 mm Hg. Hypertension was defined from self-reported history or when systolic blood pressure was ≥140 mm Hg or diastolic blood pressure was ≥90 mm Hg. Hypercholesterolemia was defined when the fasting serum cholesterol level was ≥200 mg/dL. Because the study involved routinely collected medical data, it was not necessary to obtain individual participant consent.

All statistical analyses were conducted in a gender-specific manner. Age- and BMI-adjusted means of the WBC count for each category of smoking exposure were calculated. The cutoff point for a high WBC count was determined as 7,500 cells/mm³, which corresponded to the 75th percentile.¹¹⁾ Multiple logistic regression analysis was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for high WBC counts, and the 95% CIs were examined according to the five categories of smoking exposure, seven categories of BMI, three categories of fasting serum glucose levels (normal, impaired fasting glucose, and type 2 diabetes), three categories of blood pressure (normal, pre-hypertension, and hypertension), and four categories of serum cholesterol levels (<160, 160–199, 200–239, and ≥240 mg/dL). Similarly, age-adjusted proportions of high WBC count per 1,000 persons were calculated and directly standardized to the age distribution of the Korean population in 1995. Further, we explored a possible interactive effect among smoking status, BMI, and gender-influenced metabolic risks on WBC count by using multiple logistic regression analysis. The potential interaction between cigarette smoking and BMI was tested by the multiplicative method. All analyses were conducted using SAS statistical software ver. 8.2 (SAS Institute Inc., Cary, NC, USA). All statistical tests were two-sided and statistical significance was determined at P-value <0.05.