Lung cancer is the most common cancer in the world (1) and is the leading cause of cancer deaths in Korea (2). It is estimated that lung cancer will continue to be the leading cause of cancer deaths among Korean people for the next 20 yr (3, 4).

While the epidemiological evidence linking smoking to risk of lung cancer is extensive (5), there are several reports that smoking is the important risk factor of lung cancer in Koreans (4, 6, 7). However, studies by Kim et al. (4) and Jee et al. (6) focused on mortality instead of the incidence of lung cancer. And the baseline information for the study by Yun et al. (7) as well as the previous two studies (4, 6) was obtained from a secondary source constructed by a business program of the National Health Insurance Corporation in spite of the outcome as the incidence of lung cancer. In order to estimate the magnitude of association between smoking and lung cancer in Koreans more exactly, a population-based prospective cohort study with a focus on the cancer incidence using a primary source was needed.

Thus, this study was designed to add to the body of knowledge regarding smoking habits and lung cancer risk in Korean men based on a population-based prospective cohort study.

During the total 125,053 person-years of follow-up, 78 newly diagnosed cases of lung cancer were identified from the 14,272 study participants. Table 1 gives the results of univariate analysis for potential confounders including age at entry. While there was a statistical difference between groups by age at entry, intake of coffee showed a positive significant association and dose-response relationship. The cRR of intake of raw fish, tomato, and retinol indicated their protective value.

Table 2 shows the cRR of four variables related to smoking habits-smoking status, duration of smoking, amounts of daily smoking, and TCI. The cRR of current smokers, duration of smoking over 31 yr, amounts of daily smoking over 31 cigarettes, and the total cigarette index over 35 pack-year were 5.12, 16.05, 6.31, and 13.25, respectively. In other words, current smokers, a longer duration of smoking, larger amounts of daily smoking, or a higher total cigarette index exhibited higher risk of lung cancer.

When age at entry, intake of coffee, raw fish, tomato, and retinol were controlled as potential confounders based on the results of Table 1, the aRR in current smokers, duration of smoking over 31 yr, amounts of daily smoking over 31 cigarettes, and total cigarette index over 35 pack-year were 4.18, 6.97, 4.79, and 8.55, respectively (Table 3). These observations were interpreted that four variables of smoking habits showed the statistical significance and dose-response relationship even after adjusted for confounders.

It is important to identify factors that influence a smoker's risk of developing lung cancer in order to better understand the etiology of the disease, and to more effectively target high-risk individuals for prevention and screening interventions.

The etiological role of cigarette smoking in inducing lung cancer has been well known since the early 1950s and constitutes the largest body of scientific evidence on the carcinogenic effects in humans from exposure to chemicals (5). In addition to the fact that about 90% of cases are thought to be tobacco-related (16), there is a clear dose-response relationship between lung-cancer risk and the number of cigarettes smoked per day, degree of inhalation, and age at initiation of smoking (17, 18). While the risk estimates for lung cancer reported by the large cohort studies range approximately between 7 and 15 (19, 20), the relative risk from this study was 4.18.

Such a large heterogeneity of results was considered to be associated with three major sources of variation: factors inherent to the studies such as study design, response rates, and statistical power; characteristics of smoking habits in the different population studies; and differential distribution of confounders and effect modifiers (21). First of all, the interpretation of results should involve the study design because the apparent decrease of the ORs is related to the artefact of the relative risk comparison, which tends to mask the freezing of the absolute risk at the time of quitting smoking. Second issue as various smoking habits in the different population would be related with the fact that Asian men has a lower number of cigarette smoked per day rather than Western men and the prevalence of smoking began to rise in the 1960s and 1970s (6). Based on these backgrounds, the effect of smoking is consistently lower in Asian countries than in studies of smokers in several western countries (16, 19). The final issue about differential distribution of confounders and effect modifiers could be considered by various risk estimates of previous studies in Korean men. While the RR of Jee et al. (6) and Yun et al. (7) were 4.0 (95% CI: 3.5-4.4) and 3.83 (95% CI: 2.97-4.94), respectively, these studies were conducted using secondary databases. In other words, the two studies used the data collected as part of an insurance plan so that the validity of self-reported smoking information was suspected of doubt and the adjustment for confounders or effect modifiers should be limited (6). On the other hand, this study used the primary database constructed to investigate risk factors of major cancers in Korean men. In addition to the merit above, this study assessed the incidence of lung cancer. If a study was based on cancer mortality data, the effect of smoking on the cancer incidence might have been confounded by its effect on other fatal diseases, such as cardiovascular disease (22).

In spite of these strengths, this study had some limitations. Firstly, the cohort participants were restricted as men aged between 40 and 59 yr-old at entry. Because of this reason, age at the latest follow-up was not different according to occurring lung cancer. The inference of results should be restricted for middle-aged men. Secondly, a chance of misclassification of grouping in self-reported smoking habits could not be excluded even if the validity studies were done at cohort constructed. Especially, we disclosed a never smoker in the questionnaire as a total consumption in the whole life of less than 20 cigarettes, but misclassification of current smokers as never smokers in this study could result in an underestimated cancer risk.

In conclusion, this study reconfirmed that smoking increases the risk of lung cancer in middle aged Korean men by 4.18-fold. Because the health burden from smoking-related lung cancer among Korean men will increase in the near future, anti-smoking program should be done strongly.