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Originally published as JCO Early Release 10.1200/JCO.2008.17.0498 on October 6 2008 © 2008 American Society of Clinical Oncology. Reduction and Cessation of Cigarette Smoking and Risk of Cancer: A Cohort Study of Korean Men
From the Department of Family Medicine, Samsung Medical Center, and Center for Clinical Research, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine; Department of Epidemiology, School of Public Health, Seoul National University; Department of Cancer Epidemiology and Cancer Prevention, National Cancer Center; and the Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Corresponding author: Hong-Jun Cho, MD, MPH, PhD, Department of Family Medicine, Asan Medical Center, 388-1 Poongnap-dong Songpa-gu, Seoul 138-736 Korea; e-mail: hjcho{at}amc.seoul.kr
Purpose Reducing cigarette smoking has been proposed as a method of harm reduction. The effect of smoking reduction on cancer risk has not been studied in Asian populations. Patients and Methods A total of 479,156 Korean men, age 30 to 58 years, were stratified into nine groups based on smoking status in 1990 and 1992. From 1992 to 2003, patients were observed and tested for the occurrence of cancer.
Results There was no association between smoking reduction and risk of all cancers. However, the risk of smoking-related cancers tended to decrease, though not significantly, when heavy smokers ( Conclusion Smoking reduction was associated with a significant decrease in the risk of lung cancer, but the size of risk reduction was disproportionately smaller than that expected from the reduced amount of cigarette consumption. Although smoking cessation should be the cornerstone of preventing smoking-related cancers, smoking reduction could be considered as a strategy to supplement smoking cessation for those who are unable to quit smoking immediately.
Tobacco use increases the risk of cancer of the lung, lower urinary tract, upper aerodigestive tract, and pancreas, as well as the risk of acute leukemia.1 Approximately 16% of all cancers worldwide,2 30% of all cancer deaths in the United States,3 and 37% of cancer mortality in Korean men4 are attributable to cigarette smoking. Smoking cessation substantially reduces the risk of smoking-related cancers5 of the lung,6-10 larynx,11,12 esophagus,13 and pancreas, and is the most effective method for reducing the risk of cancer among smokers.14 However, despite the availability of effective smoking cessation treatments for more than two decades, smoking cessation rates remain low.15 This is probably because cessation strategies are only effective for some smokers, whereas others remain unable to quit or do not want to quit. Harm reduction strategies aim to reduce the adverse health effects of tobacco use in individuals who are unable or unwilling to quit. Reducing the frequency of cigarette smoking is one of several harm reduction strategies.16 However, several limitations of smoking reduction strategies have been raised, including the uncertainty of health benefits.17 Recently, some researchers have examined whether smoking reduction can reduce risks for smoking-related diseases. These studies showed that smoking reduction was associated with a small reduction in lung cancer mortality,18 but had no apparent effect on all-cause mortality, fatal and nonfatal myocardial infarction, risk of stroke, and all-cancer mortality.19-22 Despite the high prevalence of smoking in Asian populations,23 no studies have investigated the effects of smoking reduction on the risk of cancer for Asians. A recent national survey found that 52.3% of Korean men smoke cigarettes,24 one of the highest rates in the world. We conducted a cohort study of Korean men to examine the effects of smoking reduction and cessation on the risk of all cancers, smoking-related cancers, and lung cancer. The large size of our study population, from the Korea National Health Insurance System, provides a unique opportunity to evaluate the effects of smoking reduction as a result of the high prevalence of smoking in Korea and the large number of outcome events.
Study Participants Study participants were Korean male civil servants, age 30 to 58 years, who had available data on their smoking status in two consecutive biennial health examinations (1990 and 1992) that were provided by the Korea National Health Insurance System. Details have previously been published.25 Among a total of 518,155 men, we excluded 2,005 who were diagnosed with cancer before the study and 9,798 for whom data on covariates were missing. We also excluded 27,634 men who reported themselves as never having smoked or as ex-smokers in 1990 but as smokers in 1992. Thus a total of 479,156 men (92.5%) were included in the analysis.
Measurements
The amount of ethanol ingested per week was calculated from the drinking frequency per week, the typical amount consumed at each sitting, and the ethanol quantity on the gram weight in the most popular Korean liquor, soju. Participants were categorized into four groups based on weekly alcohol consumption: less than 30, 30 to 104, 105 to 209,
Body mass indexes (BMIs) were determined when participants were wearing light clothing and no shoes. BMI was categorized into four groups according to WHO criteria: less than 18.5, 18.5 to 24.9, 25 to 29.9, and
Outcome Measurement Cancer cases were identified through data linkage with Korea Central Cancer Registry (KCCR) data, Serious Disease Registry (SDR) data of the Korea National Health Insurance System, and death report data of the Korean National Statistical Office using a unique personal identification number. KCCR is a hospital-based cancer registration system that began in 1978. The percentage of participating KCCR-registered hospitals was 74%, 79%, and 79% in 1995, 1999, and 2002, respectively.27 We also used data from the SDR, a nationwide registry that identifies residents with cancer and other serious diseases to help them with medical expenses. With SDR data, an additional 690 cancer cases (3.79% of all identified cancer cases) were identified.
Analytic Methods
We followed participants for a mean of 10.7 years (standard deviation, 1.3 years) between 1992 and 2003, yielding a total of 5,142,484 person-years. During this period, there were 18,196 cancer events, 52% (9,470 cases) of which were smoking-related cancers and 11.3% (2,063 cases) of which were lung cancer. Table 1 shows changes in smoking status among participants. In 1990, 2 years before initiation of the study, 63.3% of all participants smoked, 27.3% were heavy smokers, 43.2% were moderate smokers, and the remaining 29.5% were light smokers. During the 2 years before initiation of the study (1990 through 1992), 24.4% of heavy smokers and 14.6% of moderate smokers reduced their levels of smoking. During the same period, 5.9% of heavy smokers, 8.0% of moderate smokers, and 14.0% of light smokers stopped smoking.
Table 2 shows baseline characteristics (measured in 1992) according to the change in smoking status between 1990 and 1992. A comparison of nonreducing heavy smokers with those who reduced their smoking level (from heavy to moderate or heavy to light) revealed that reducers tended to be older, shorter, have lower BMIs, engage in more regular exercise, consume less alcohol, and have lower incomes.
Table 3 shows the associations between change in smoking status and risk of cancer. The risk of any type of cancer was not significantly reduced for heavy smokers who reduced their smoking. However, the risk of smoking-related cancers tended to decrease for heavy smokers who became moderate smokers (HR = 0.91; 95% CI, 0.82 to 1.02). This trend did was not maintained when the analysis was limited to a subgroup who reported persistent smoking status up to 1994 (HR = 1.00; 95% CI, 0.87 to 1.15). Compared with men who were sustained heavy smokers, the risk of lung cancer decreased by 28% (95% CI, 11% to 41%) for men who reduced from heavy to moderate smoking and by 37% (95% CI, 14% to 54%) for men who reduced from heavy to light smoking. The association between the reduction of smoking and the risk of lung cancer did not materially change when the earlier cancer cases were excluded from the analysis to avoid the so-called ill-reducer effect. When the analysis was limited to those whose smoking status in 1992 was maintained up to 1994, the risk of lung cancer for men who reduced from heavy to light smoking decreased by 55% (95% CI, 4% to 79%) compared with sustained heavy smokers. Reduction of smoking among moderate smokers was also associated with lower risk of lung cancer compared with nonreducing moderate smokers.
Among the three classes of nonreducers (heavy, moderate, and light), compared with heavy smokers, moderate and light smokers had significantly lower risks of all cancers (7% lower for moderate smokers, 12% lower for light smokers), smoking-related cancers (18% lower for moderate smokers, 29% lower for light smokers), and lung cancer (43% lower for moderate smokers, 52% lower for light smokers). Never smokers, sustained ex-smokers, and quitters between 1990 and 1992 showed significantly lower risk of all cancers (40% lower for never smokers, 23% lower for ex-smokers, and 11% lower for quitters), smoking-related cancers (62% lower for never smokers, 47% lower for ex-smokers, and 36% lower for quitters), and lung cancer (87% lower for never smokers, 79% lower for ex-smokers, and 67% lower for quitters) also in a dose-response way, compared with nonreducing heavy smokers.
In this large cohort study of Korean male smokers, we found that reduction from heavy to moderate or light smoking was associated with a significant decrease in lung cancer risk. These results are similar to the findings of a study in Denmark18 and suggest that smoking reduction may be used as a strategy of reducing the risk of lung cancer for those who are unable to quit smoking immediately. A previous study of Danish men and women showed a trend toward a decrease in risk of mortality from tobacco-related cancers after reduction of smoking.19 When we evaluated the incidence of smoking-related cancers among Korean men, we found a similar trend. Although neither of these findings was statistically significant, they support a possible favorable effect of smoking reduction. However, our study showed that the amount of lung cancer risk reduction was not in proportion to the amount of reduction in cigarette consumption, and reducing from heavy to light smoking (corresponding to > 50% reduction in cigarette consumption) only resulted in a 37% decrease in the risk of lung cancer. Moreover, men who reduced from heavy to light smoking had higher risks of all cancers, smoking-related cancers, and lung cancer when compared with sustained light smokers in our study. These findings suggest that just a reduction in smoking amount could not result in enough risk reduction, and quitting smoking should be the cornerstone of preventing smoking-related cancers. Two possible explanations can be proposed regarding reduction in lung cancer risk by smoking reduction. First, smoking reduction can be a way station to permanent quitting,28 and the reduction of lung cancer risk among reducers could be partly attributable to their increased probability of cessation. A person who has reduced cigarette consumption tended to quit smoking more frequently than nonreducing smokers in previous studies.29,30 A Danish study also showed that 20% of reducers stopped smoking when they were observed further.18 In our study, daily amount of cigarette consumption was inversely related to the quit-smoking rate, which is compatible with those findings from Western studies.31 Second, reduction in consumed amount of cigarettes per se could be another explanation for the decreased risk of lung cancer among reducers. Given the well-established dose-response association between amount of cigarette smoking and lung cancer risk,1 it is likely that reduction in smoking consumption could decrease the risk of lung cancer, probably through the lowered level of tobacco-specific lung carcinogens. However, it is well known that this effect is diminished by compensatory inhalation. The reduced level of tobacco-specific lung carcinogens is not directly proportional to the amount of reduction in cigarette consumption (and sometimes was transient32), presumably because smokers who are reducing tend to inhale more intensely to maintain nicotine concentrations in the blood.33 A previous study found that the level of metabolites of tobacco-specific lung cancer carcinogens in those who reduced to light smoking was more than twice that present in sustained light smokers.34 In this regard, the disproportionate reduction of lung cancer risk compared with the reduced amount of smoking consumption shown in our study are compatible with the findings from these previous studies that evaluated biochemical aspects of smoking reduction.32,34 Our study confirms that compared with smokers, quitters, ex-smokers, and never smokers had significantly lower risks of all cancers, smoking-related cancers, and lung cancer. This has been previously reported in numerous studies of Western populations.5-9,35 Our study has certain limitations that must be considered. First, we assessed smoking level using a questionnaire with predetermined response categories and were therefore unable to calculate the exact amount of smoking reduction. This might have led to an underestimate of the effects of smoking reduction, especially among men who changed from heavy to a moderate or moderate to a light smoking level. Second, we did not perform a biologic validation of self-reported smoking status, so over-reporting of smoking reduction is possible. In fact, this seems likely, because the proportion of heavy smokers who reportedly reduced their cigarette consumption was higher (close to 25%) than observed in a previous study.19 If so, this would lead to an underestimation of the effects of smoking reduction on the risks of cancers. Third, smoking status can change over time and this may cause an under- or overestimation of the effects of smoking reduction. For example, a previous study showed that only 50% of Danish people who reduced their level of smoking maintained this lower level after 10 years, whereas 30% returned to their original level.19 Unfortunately, we did not have data on smoking status at multiple time points up to the time of cancer occurrence. Thus there is a possibility that we underestimated the effect of smoking reduction on lung cancer risk. In fact, this seems likely because the risk of lung cancer for men who reduced from heavy or moderate to light smoking decreased more when the analysis was limited to those who maintained smoking status up to 1994. Fourth, in this study we identified incident cancer cases from the KCCR, a nationwide hospital-based cancer registry system that includes 79% of registered hospitals in 2002 and approximately 90% of the incident cancer cases.27 Even though there could be some underreporting of cancers, we have no reason to believe that this would differ significantly for men with different smoking status. In conclusion, we found that smoking reduction was associated with a significant decrease in the risk of lung cancer and shows a trend toward a decreased risk of smoking-related cancers for a cohort of Korean male smokers, but the size of risk reduction was disproportionately smaller than that expected from the reduced amount of cigarette consumption. Because even smoking as few as one to four cigarettes per day can be hazardous,36 smoking cessation is clearly the most effective approach for prevention of smoking-related cancers. However, our results suggest that smoking reduction can be an effective strategy for those who are unable to quit smoking.
The author(s) indicated no potential conflicts of interest.
Conception and design: Yun-Mi Song, Hong-Jun Cho Administrative support: Joohon Sung, Hong-Jun Cho Provision of study materials or patients: Yun-Mi Song, Joohon Sung Collection and assembly of data: Yun-Mi Song, Joohon Sung Data analysis and interpretation: Yun-Mi Song, Joohon Sung, Hong-Jun Cho Manuscript writing: Yun-Mi Song, Joohon Sung, Hong-Jun Cho Final approval of manuscript: Yun-Mi Song, Joohon Sung, Hong-Jun Cho
published online ahead of print at www.jco.org on October 6, 2008. Supported by Grant No. SBRI C-A7-416-1 from the Samsung Biomedical Research Institute, Grant No. 0610552-2 from the National Cancer Center, and Grant No. 01-PJ1-PG1-01CH10-0007 Ministry of Health and Welfare, Korea. The sponsors had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Rockville, MD, United States Department of Health and Human Services, Public Health Service, Centers for Disease Control, Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 1990 6. Anthonisen NR, Skeans MA, Wise RA, et al: The effects of a smoking cessation intervention on 14.5-year mortality. Ann Intern Med 142:233-239, 2005 7. Ebbert JO, Yang P, Vachon CM, et al: Lung cancer risk reduction after smoking cessation: Observations from a prospective cohort of women. J Clin Oncol 21:921-926, 2003 8. Huxley R, Jamrozik K, Lam TH, et al: Impact of smoking and smoking cessation on lung cancer mortality in the Asia-Pacific region. Am J Epidemiol 165:1280-1286, 2007 9. Peto R, Darby S, Deo H, et al: Smoking, smoking cessation, and lung cancer in the UK since 1950: Combination of national statistics with two case-control studies. BMJ 321:323-329, 2000 10. 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Eur J Gastroenterol Hepatol 14:1343-1353, 2002[CrossRef][Medline] 15. United States Department of Health and Human Services: Reducing Tobacco Use: A Report of the Surgeon General. Atlanta, GA, United States Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2000 16. McNeill A: Harm reduction. BMJ 328:885-887, 2004 17. Hughes JR: Reduced smoking: An introduction and review of the evidence. Addiction 95:S3-S7, 2000 (suppl 1)[CrossRef][Medline] 18. Godtfredsen NS, Prescott E, Osler M: Effect of smoking reduction on lung cancer risk. JAMA 294:1505-1510, 2005 19. Godtfredsen NS, Holst C, Prescott E, et al: Smoking reduction, smoking cessation, and mortality: A 16-year follow-up of 19,732 men and women from the Copenhagen Centre for Prospective Population Studies. Am J Epidemiol 156:994-1001, 2002 20. Godtfredsen NS, Osler M, Vestbo J, et al: Smoking reduction, smoking cessation, and incidence of fatal and non-fatal myocardial infarction in Denmark 1976-1998: A pooled cohort study. J Epidemiol Community Health 57:412-416, 2003 21. Tverdal A, Bjartveit K: Health consequences of reduced daily cigarette consumption. Tob Control 15:472-480, 2006 22. Song YM, Cho HJ: Risk of stroke and myocardial infarction following reduction or cessation of cigarette smoking: A cohort study in Korean men. Stroke doi:10.1161/STROKEAHA.107.512632 23. Mackay J, Eriksen M, Shafey O: The Tobacco Atlas (ed 2). Atlanta, GA, American Cancer Society, 2006 24. Ministry of Health and Welfare: The Third Korea National Health and Nutrition Examination Survey (KNHANES III) 2005: Health Behaviors of Adults. Seoul, Korea, Ministry of Health and Welfare, 2007 25. Song YM, Sung J, Lawlor DA, et al: Blood pressure, haemorrhagic stroke and ischaemic stroke: The Korean national prospective occupational cohort study. BMJ 328:324-325, 2004 26. World Health Organization: Obesity: Preventing and managing the global epidemic. Geneva, Switzerland, World Health Organization, 1998 27. National Cancer Center: Number of hospitals participating in Korea Central Cancer Registry, 2/08 update. http://www.ncc.re.kr/ 28. McCarthy WJ, Zhou Y, Hser YI: Individual change amid stable smoking patterns in polydrug users over 3 years. Addict Behav 26:143-149, 2001[CrossRef][Medline] 29. Hyland A, Levy DT, Rezaishiraz H, et al: Reduction in amount smoked predicts future cessation. Psychol Addict Behav 19:221-225, 2005[CrossRef][Medline] 30. Wennike P, Danielsson T, Landfeldt B, et al: Smoking reduction promotes smoking cessation: Results from a double blind, randomized, placebo-controlled trial of nicotine gum with 2-year follow-up. Addiction 98:1395-1402, 2003[CrossRef][Medline] 31. Hyland A, Li Q, Bauer JE, et al: Predictors of cessation in a cohort of current and former smokers followed over 13 years. Nicotine Tob Res 6:S363-S369, 2004[Abstract] 32. Hecht SS, Murphy SE, Carmella SG, et al: Effects of reduced cigarette smoking on the uptake of a tobacco-specific lung carcinogen. J Natl Cancer Inst 96:107-115, 2004 33. Hatsukami DK, Kotlyar M, Allen S, et al: Effects of cigarette reduction on cardiovascular risk factors and subjective measures. Chest 128:2528-2537, 2005[CrossRef][Medline] 34. Hatsukami DK, Le CT, Zhang Y, et al: Toxicant exposure in cigarette reducers versus light smokers. Cancer Epidemiol Biomarkers Prev 15:2355-2358, 2006 35. Doll R, Peto R, Boreham J, et al: Mortality in relation to smoking: 50 years’ observations on male British doctors. BMJ 328:1519, 2004 36. Bjartveit K, Tverdal A: Health consequences of smoking 1-4 cigarettes per day. Tob Control 14:315-320, 2005 Submitted March 5, 2008; accepted June 13, 2008.
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
20 cigarettes/d) became moderate smokers (10 to 19 cigarettes/d), with a hazard ratio (HR) of 0.91 (95% CI, 0.82 to 1.02). For lung cancer, patients who reduced from heavy to moderate smoking and from heavy to light smoking (< 10 cigarettes/d) had significantly decreased risks based on multivariable-adjusted HRs (HR = 0.72, 95% CI, 0.49 to 0.89; HR = 0.63, 95% CI, 0.46 to 0.84, respectively). Study participants who never smoked, sustained ex-smokers, and quitters had lower risks for all cancers, smoking-related cancers, and lung cancer in a dose-response manner as compared with heavy smokers. 
