Japanese Journal of Clinical Oncology Advance Access originally published online on March 1, 2007
Japanese Journal of Clinical Oncology 2007 37(3):168-174; doi:10.1093/jjco/hyl146
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© 2007 Foundation for Promotion of Cancer Research
Alcohol Drinking and Lung Cancer Risk: An Evaluation Based on a Systematic Review of Epidemiologic Evidence among the Japanese Population
1 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya
2 Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, Gifu
3 Department of Epidemiology, Research Institute, International Medical Center of Japan, Tokyo
4 Department of Preventive Medicine, Saga Medical School, Faculty of Medicine, Saga University, Saga
5 Division of Epidemiology, Miyagi Cancer Center Research Institute, Natori, Miyagi
6 Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai
7 Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
For reprints and all correspondence: Kenji Wakai, Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. E-mail: wakai{at}aichi-cc.jp
Received August 23, 2006; accepted October 23, 2006
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Abstract |
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 TOP Abstract INTRODUCTIONMETHODSMAIN FEATURES AND COMMENTSEVALUATION OF EVIDENCE ON...Conflict of interest statementReferences |
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Background: The relationship between alcohol consumption and risk of lung cancer is controversial. Based on a systematic review of epidemiologic evidence, we evaluated this association among the Japanese population, who may be more susceptible to alcohol-related diseases than Western populations.
Methods: Original data were obtained from MEDLINE searches using PubMed or from searches of the Ichushi database, complemented with manual searches. The evaluation of associations was based on the strength of evidence and the magnitude of association, together with biological plausibility as previously evaluated by the International Agency for Research on Cancer.
Results: We identified seven cohort studies and two case-control studies. One cohort study demonstrated a strong positive association between alcohol drinking and the risk of female lung cancer, but the association almost disappeared after adjustment for smoking. The other eight studies showed a weak positive or no association. Although smoking is the best-established risk factor for lung cancer, only five cohort studies presented smoking-adjusted risks out of all nine identified. Furthermore, only two studies explicitly reported the risk estimate for ex-drinkers who may have quit alcohol drinking after the development or diagnosis of the disease and have an apparently higher risk.
Conclusion: We conclude that the epidemiologic evidence on the association between alcohol drinking and lung cancer risk remains insufficient in terms of both the number and methodological quality of studies among the Japanese population.
Key Words: systematic review • epidemiology • alcohol drinking • lung neoplasms • Japanese
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INTRODUCTION |
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Although alcohol consumption is an established risk factor for cancers of the oral cavity, pharynx, larynx, esophagus and liver (1), its relationship with lung cancer still remains controversial. The review of epidemiologic studies by the World Cancer Research Fund and the American Institute for Cancer Research concluded in 1997 that alcohol drinking possibly increases the risk of lung cancer (1). According to the review article by Bandera et al. (2) of 2001, there was an increasing body of literature suggesting that alcoholic beverages may increase lung cancer risk after adjustment for cigarette smoking.
More recently, Korte and coworkers (3) indicated, based on their meta-analysis, that after controlling for cigarette smoking, evidence of an association between alcohol consumption and lung cancer is largely limited to groups consuming 
2000 g of ethanol per month (2.9 Japanese drinks [gou] per day). Freudenheim et al. (4) found a 21 and 16% greater risk of lung cancer for the drinkers of 30 g alcohol per day than that for non-drinkers in men and women, respectively, in a pooled analysis of cohort studies. Most of the studies included in these analyses, however, were conducted in Western countries, where the types of alcoholic beverages consumed are quite different from those in Japan. Furthermore, Japanese may be more susceptible to alcohol in terms of carcinogenesis because the aldehyde dehydrogenase 2 (ALDH2) Glu487Lys polymorphism is more common in Japanese than in Western populations (5,6). The 487Lys allele results in a lower ALDH2 activity and a higher blood concentration of acetaldehyde (5), which is the initial metabolite of alcohol shown to be carcinogenic in animal experiments (7).
We therefore attempted to review epidemiologic studies on alcohol drinking and lung cancer risk in Japanese populations. This report is one among a series of articles by our research group, who are investigating the association of lifestyles with the risks of total and major specific cancers in Japan (8).
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METHODS |
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TOPAbstractINTRODUCTIONMETHODSMAIN FEATURES AND COMMENTSEVALUATION OF EVIDENCE ON...Conflict of interest statementReferences |
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The original data for this review were identified by searches of MEDLINE using PubMed and by those of the Ichushi (Japana Centra Revuo Medicina) database, complemented by manual searches of references from relevant articles when necessary. We identified all epidemiologic studies on the association between alcohol drinking and lung cancer incidence or mortality among Japanese published from January 1980 to June 2006, using the search words ‘alcohol’, ‘drinking’, ‘lung cancer’, ‘case-control studies’, ‘cohort studies’, ‘Japan’ and ‘Japanese’. Papers written in either English or Japanese were reviewed. Only studies on Japanese populations living in Japan were included. The individual results were summarized in the tables separately according to study design as cohort or case-control studies.
We evaluated the studies based on the magnitude of association and the strength of evidence. First, the hazard ratios, rate ratios, or odds ratios in each epidemiologic study were grouped by the magnitude of association, considering statistical significance (SS) or no statistical significance (NS), into: strong (symbol 
or 
), < 0.5 or > 2.0 (SS); moderate (symbol or ), either (1) < 0.5 or > 2.0 (NS), (2) > 1.5–2.0 (SS), or (3) 0.5 to < 0.67 (SS); weak (symbolor ), either (1) > 1.5–2.0 (NS), (2) 0.5 to < 0.67 (NS), or (3) 0.67–1.5 (SS); or no association (symbol —), 0.67–1.5 (NS). We thus defined the magnitude of association by its strength, that is, the size of hazard ratios, rate ratios, or odds ratios for the highest intake category of the group of current or ever drinkers versus non- or never drinkers, and its statistical significance. Two-sided P values less than 0.05 were considered statistically significant. In the case of multiple publications of analyses of the same or overlapping datasets, only data from the largest or most updated results were included.
After this process, the strength of evidence was evaluated in a similar manner to that used in the WHO/FAO Expert Consultation Report (9), in which evidence was classified as ‘convincing’, ‘probable’, ‘possible’ and ‘insufficient’. We assumed that biological plausibility, based on evidence in experimental animals and mechanistic and other relevant data, corresponded to the judgment of the most recent evaluations from the International Agency for Research on Cancer (IARC) (10). Notwithstanding the use of this quantitative assessment rule, an arbitrary assessment cannot be avoided when considerable variation exists in the magnitude of association between the results of each study. The final judgment was made based on a consensus of the research group members, and it was therefore not necessarily objective. To assure the validity of the systematic review, at least seven authors of the article checked the evidence tables (Tables 1 and 2 in this paper) and the summary tables (Tables 3 and 4) with other members of our research group, in order to make conclusions based on consensus.
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MAIN FEATURES AND COMMENTS |
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We identified seven cohort studies (Table 1) (11–17) and two case-control studies (Table 2) (18,19). One additional cohort study was found (20), but its subjects were derived from a subgroup of the other study, that is, the Japan Collaborative Cohort Study (17). We therefore did not include this additional study in our review. Among the seven cohort studies, one presented results by gender (12), five for only men (11,13,14,16,17), and one for both genders combined (15). Both of the two case-control studies reported results for men and women combined (18,19).
We found three articles that mentioned the effect modification by alcohol drinking on the risk of smoking or the interaction between smoking and drinking habits. Kono et al. (11) reported no interaction between the two habits (P for interaction, 0.84). Murata and colleagues (14) stated that the elevated risk in smokers was consistently seen at all levels of alcohol consumption; the odds ratios for current smokers compared with never or former smokers (calculated from the published data) were 3.9, 2.2 and 2.6 for men who consumed 0, 0.1–1.0, and 1.1 + Japanese drinks (gou) per day, respectively. Nishino and coworkers (17) reported that there was no significantly increased risk of lung cancer associated with current alcohol consumption, regardless of smoking status in the stratified analysis. The statistical power of this analysis, however, was limited due to the small number of lung cancer deaths in most categories.
The magnitude of association for these studies is summarized in Tables 3 and 4 for cohort and case-control studies, respectively. The cohort study by Hirayama (12) demonstrated a strong positive association () between alcohol drinking and the risk of female lung cancer. The author, however, stated that the clear association in women almost disappeared after adjusting for smoking. The other eight studies showed a weak positive () (14,18) or no (11,13,15–17,19) association. Even in moderate to heavy drinkers who consumed more than 40 g of alcohol per day, no study found a significantly increased risk.
Some issues should be considered when examining the association of drinking habits with lung cancer risk. One is the confounding by smoking of the best-established risk factor for cancer (21). Since alcohol drinking often coexists with smoking (16,17), confounding by smoking will seemingly elevate the risk by alcohol consumption. Of all the nine studies identified, only five cohort studies (11,13,15–17) presented smoking-adjusted risks.
Diet may also be an important confounding factor (2). Because of the caloric content of alcoholic beverages, their consumption may displace other foods and nutrients from the diet, especially in heavy drinkers (16,17). Several foods and nutrients, such as vegetables, fruits, and carotenoids, potentially decrease the risk of lung cancer (1), so that the risk might be overestimated in drinkers if dietary factors are not considered. Only two studies (16,17) out of all the articles reviewed reported risk estimates allowing for dietary intakes.
Another issue concerns former drinkers (22). Patients with lung cancer may quit alcohol drinking after the development or diagnosis of the disease, which would result in an apparently higher risk in ex-drinkers. In fact, Nakaya et al. (16) and Nishino et al. (17) found a significantly increased risk among former drinkers (Table 1). If ex-drinkers are grouped into the reference category with never drinkers as in some studies (11,14), the risk for current drinkers will be underestimated. Only the studies by Nakaya et al. (16) and by Nishino and coworkers (17) explicitly reported the risk estimate for ex-drinkers. Publication bias should also be considered, but it seems to be unlikely to exist, because only one study by Nishino et al. (17) initially aimed at examining the association of alcohol drinking with lung cancer risk.
Finally, studies evaluating the effect of alcohol on lung cancer by beverage type more frequently found a positive association with beer and liquor than with wine in countries other than Japan (2,4). Because only one study (13) in our review showed the smoking-adjusted risk by beverage type and the number of lung cancer cases of this study was too small, further investigations are required to examine the separate effects of the various alcoholic drinks in Japanese populations. The role of sake (Japanese rice wine) in the development of lung cancer should specifically be clarified because sake is one of the major alcoholic beverages in Japan and is not popular in other countries.
The IARC evaluation (10) concluded that there was sufficient evidence for the carcinogenicity of acetaldehyde, the major metabolite of ethanol, in experimental animals. In addition, although experimental evidence is not conclusive, experimental studies indicate that alcohol itself does not initiate cancer but may potentiate the effect of carcinogens by a number of mechanisms, including facilitation of cellular entry of carcinogens and/or affecting their metabolism, inhibition of DNA repair, and tumor promotion (23). In the IARC evaluation (10), it was noted that ethanol enhanced the incidence of lung tumors induced in mice by N-nitrosodiethylamine or N-nitrosodi-n-propylamine.
In summary, epidemiologic evidence for the association of alcohol drinking with lung cancer risk in Japan still remains inconclusive due both to the number and methodological quality of the studies, although some experimental studies have supported the biological plausibility of the association. Further epidemiologic investigations should be conducted considering confounding by smoking and diet, excluding former drinkers from the reference group, and taking the type of alcoholic beverages into account.
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EVALUATION OF EVIDENCE ON ALCOHOL DRINKING AND LUNG CANCER RISK IN JAPANESE |
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TOPAbstractINTRODUCTIONMETHODSMAIN FEATURES AND COMMENTSEVALUATION OF EVIDENCE ON...Conflict of interest statementReferences |
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From these results and based on assumed biological plausibility, we conclude that the epidemiologic evidence on the association between alcohol drinking and lung cancer risk remains insufficient among the Japanese population.
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Conflict of interest statement |
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TOPAbstractINTRODUCTIONMETHODSMAIN FEATURES AND COMMENTSEVALUATION OF EVIDENCE ON...Conflict of interest statementReferences |
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None declared.
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Acknowledgments |
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The authors gratefully acknowledge the assistance of Ms Chie Yoshida, Ms Izumi Suenega, and Mr Tomohiro Shintani. This work was supported by the Third Term Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare, Japan.
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Footnotes |
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* Research group members: Shoichiro Tsugane (principal investigator), Manami Inoue, Shizuka Sasazuki, Motoki Iwasaki, Tetsuya Otani, National Cancer Center, Tokyo; Ichiro Tsuji (2004–), Yoshitaka Tsubono (2003), Taichi Shimazu, Tohoku University, Sendai; Yoshikazu Nishino, Miyagi Cancer Center, Natori, Miyagi; Tetsuya Mizoue, International Medical Center of Japan, Tokyo; Chisato Nagata, Gifu University, Gifu; Kenji Wakai, Aichi Cancer Center, Nagoya; and Keitaro Tanaka, Saga University, Saga, Japan
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References |
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