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Japanese Journal of Clinical Oncology Advance Access originally published online on June 9, 2006
Japanese Journal of Clinical Oncology 2006 36(6):387-394; doi:10.1093/jjco/hyl031
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© 2006 Foundation for Promotion of Cancer Research

Tobacco Smoking and Breast Cancer Risk: An Evaluation Based on a Systematic Review of Epidemiological Evidence among the Japanese Population

Chisato Nagata1, Tetsuya Mizoue2, Keitaro Tanaka3, Ichiro Tsuji4, Kenji Wakai5, Manami Inoue6, Shoichiro Tsugane6 Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan

1 Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, 2 Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 3 Department of Preventive Medicine, Saga Medical School, Faculty of Medicine, Saga University, Saga, 4 Division of Epidemiology, Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, 5 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya and 6 Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan

For reprints and all correspondence: Chisato Nagata, Department of Epidemiology & Preventive Medicine, Gifu University Graduate School of Medicine, Gifu, Japan, 1-1 Yanagido, Gifu 501-1194, Japan; E-mail: chisato{at}cc.gifu-u.ac.jp

Received January 30, 2006; accepted March 7, 2006


    Abstract
 TOP
 Abstract
 INTRODUCTION
 METHODS
 MAIN FEATURES AND COMMENTS
 EVALUATION OF THE EVIDENCE...
 References
 
Background: Our research group undertook an appraisal of the body of epidemiological studies on cancer in Japan to evaluate the existing evidence concerning the association between health-related lifestyles and cancer. As tobacco smoking may be one of the few modifiable risk factors for breast cancer, we focused on the association between tobacco smoking and the risk of breast cancer in this review.

Methods: A MEDLINE search was conducted to identify epidemiological studies on the association between smoking and breast cancer incidence or mortality among the Japanese from 1966 to 2005. 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: Three cohort studies and eight case-control studies were identified. The relative risk (RR) or odds ratio (OR) of breast cancer for current smokers ranged from 0.71 to 6.26 in these studies. A significantly increased risk among current smokers compared with never smokers (RR = 1.7) was reported in one out of the three cohort studies. Moderate or strong associations between smoking and breast cancer risk (OR > 2.0) were observed in four of the eight case-control studies. Experimental studies have supported the biological plausibility of a positive association between tobacco smoking and breast cancer risk.

Conclusion: We conclude that tobacco smoking possibly increases the risk of breast cancer in the Japanese population.

Key Words: systematic review • epidemiology • tobacco smoking • breast cancer • the Japanese


    INTRODUCTION
 TOP
 Abstract
 INTRODUCTION
 METHODS
 MAIN FEATURES AND COMMENTS
 EVALUATION OF THE EVIDENCE...
 References
 
Breast cancer is the most frequently diagnosed cancer in women, the incidence rate of which has increased considerably among Japanese women in recent years. The established risk factors include menstrual and reproductive history, family history of breast cancer, postmenopausal obesity, genetic susceptibility and exposure to ionizing radiation (1). Yet more than half of breast cancer risk remained unexplained. Our research group undertook an appraisal of the body of epidemiological studies on cancer in Japan to evaluate the existing evidence concerning the association between health-related lifestyles and cancer (2). Tobacco smoking may be one of the few modifiable risk factors for breast cancer. The following is a summary of information from epidemiological studies on smoking and breast cancer.


    METHODS
 TOP
 Abstract
 INTRODUCTION
 METHODS
 MAIN FEATURES AND COMMENTS
 EVALUATION OF THE EVIDENCE...
 References
 
A MEDLINE search was conducted to identify epidemiological studies on the association between smoking and breast cancer incidence or mortality among the Japanese from 1966 to 2005. Papers written in either English or Japanese were reviewed, and only studies on the Japanese populations living in Japan were included.

Individual results were summarized in tables separately by study design as cohort or case-control studies. Relative risks (RRs) or odds ratios (ORs) in each epidemiological study were grouped by magnitude of association, with consideration of statistical significance (SS) or no statistical significance (NS), as strong, <0.5 or >2.0 (SS); moderate, either (i) <0.5 or >2.0 (NS), (ii)> 1.5 to 2 (SS), or (iii) 0.5 to <0.67 (SS); weak, either (i) >1.5–2.0 (NS), (ii) 0.5 to <0.67 (NS) or (iii) 0.67–1.5 (SS); or no association, 0.67–1.5 (NS). After this process, the strength of evidence was evaluated in a similar manner to that used in the WHO/FAO Expert Consultation Report (3), in which evidence was classified as ‘convincing’, ‘probable’, ‘possible’ and ‘insufficient’. We assumed that biological plausibility corresponded to the judgment of the most recent evaluation from the International Agency for Research on Cancer (IARC) (4). 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, and incidence was given priority over mortality as an outcome measure. Details on the evaluation methods are described elsewhere (2).


    MAIN FEATURES AND COMMENTS
 TOP
 Abstract
 INTRODUCTION
 METHODS
 MAIN FEATURES AND COMMENTS
 EVALUATION OF THE EVIDENCE...
 References
 
We identified three cohort studies (57) and eight case-control studies (815). Besides these studies, two case-control studies (16,17) referred to the association between smoking and breast cancer risk in addition to their main findings. However, they were not included in this review because the data overlapped with those used for previous study conducted by the same institute. Details of the component studies including age range, study period, numbers of women enrolled, RR or OR of breast cancer for smoking status or/and number of cigarettes smoked per day and years of smoking, and covariates used in adjustment are described in Tables 1 and 2. Summaries of the magnitudes of association for these studies are shown in Tables 3 and 4.


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Table 1. Tobacco smoking and breast cancer risk, cohort study in Japanese population

 

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Table 2. Tobacco smoking and breast cancer risk, case-control study in Japanese population

 

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Table 3. Summary of the association between tobacco smoking and breast cancer risk, cohort study

 

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Table 4. Summary of the association between tobacco smoking and breast cancer risk, case-control study

 
Among the three cohort studies, a significantly increased risk among current smokers compared with never smokers was reported in one study (RR = 1.7) (7) but not in the others (Table 1). The RRs for current vs. never/non-smokers were 1.28 and 0.97 in the other two studies, respectively.

Moderate or strong associations between smoking and breast cancer risk were observed in four of the eight case-control studies (1114). The ORs of breast cancer for current or ex-smokers reported from the case-control studies ranged from 0.71 to 6.26. All the case-control studies were hospital-based except one study by Ueji et al. (14). This study reported the highest OR for current smokers. The response rates from cases and community controls were 75.5 and 67.4%, respectively in the study.

As alcohol drinking and smoking are closely associated, there is potential for confounding of alcohol use on the association between smoking and breast cancer. One of the three cohort studies (7) and two of the eight case-control studies reported associations after adjustment for alcohol use (9,15). However, in most of the other studies, information on alcohol use was obtained. Authors did not observe confounding effect of alcohol on the association between smoking and breast cancer risk. Some but not all studies took account of other known risk factors of breast cancer, such as parity, age at menarche, age at first birth, age at menopause and family history of breast cancer. However, the studies showing RRs/ORs with and without adjustment for these factors (7,8,1315) revealed that the association between smoking and breast cancer was not substantially altered.

Tobacco smoking has been suggested as a cause of breast cancer. In the evaluation of IARC (4), smoking and tobacco smoke are judged to be carcinogenic to humans. Chemical carcinogens in tobacco smoke can cause mammary tumors in animals (4,18). Metabolites of tobacco smoke have been formed in the breast fluid or tissue of smokers (19,20). Thus, it is biologically plausible that exposure to tobacco smoke is related to breast cancer. However, epidemiological studies of smoking and breast cancer have produced inconsistent results (4,2123). A recent pooled analysis of 53 epidemiological studies showed no increased risk of breast cancer associated with smoking (24). However, passive smoking has been suggested to be associated breast cancer risk rather consistently (23). Thus, the risk of active smoking may be canceled out by the passive smoking risk in the control group. Some studies suggested that longer duration or high intensity of smoking may be associated with an increased risk of breast cancer (25,26). Studies referring to years of smoking, age at smoking started or pack-years of smoking were few in the present review and implications of these factors in breast cancer risk among Japanese women were equivocal.

Unlike the previous reviews of studies among non-Japanese populations, the present review indicates a positive association between smoking and breast cancer. We have no explanation for this difference at this moment. It is unlikely that female smokers in Japan smoke more heavily and have a longer duration of smoking. Marugame et al. (27) reported that both the number of years of smoking and the number of cigarettes smoked per day were lower among Japanese smokers than those observed for smokers of both sexes in the USA. Differences in endogenous estrogen status or distribution of certain genes related to metabolic enzymes among populations may partially explain the discrepancy between the present and previous reviews. Any antiestrogenic effects of smoking may be smaller in women with low circulating estrogen levels as in the case of postmenopausal Japanese women. However, there was no consistent interaction with menopausal status in the present and previous reviews (22). Certain genotypes, such as GSTT1-null (28,29), XPD-Gly/Gly (30,31), XRCC1 Arg399Gln/Gln (31,32), CYP1A1*2A (33,34) and slow NAT2 genotypes (29,35) have been suggested to increase the risk of breast cancer among women who smoke. Concerning these genotypes, Japanese appear to have higher frequency for GSTT1-null and CYP1A1*2A but not for the others compared with Caucasians (3638). Confounding by other unmeasured factors, such as diet including phytoestrogen intake, cannot be excluded.

Integration of evidence based on case-control studies is compromised because of limitations in participants' memory of past exposure history and selection biases introduced in the recruitment of cases and controls. There was a tendency that positive association was reported in the case-control studies with small sample size. In addition, we cannot exclude the effect of publication bias. The number of cohort studies is insufficient to draw a definite conclusion.


    EVALUATION OF THE EVIDENCE ON TOBACCO SMOKING AND BREAST CANCER RISK IN JAPANESE
 TOP
 Abstract
 INTRODUCTION
 METHODS
 MAIN FEATURES AND COMMENTS
 EVALUATION OF THE EVIDENCE...
 References
 
From these results and assumed biological plausibility, we conclude that tobacco smoking possibly increases the risk of breast cancer in the Japanese population.


    Acknowledgments
 
This work was supported by the Third Term Comprehensive 10 year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare, Japan.


    References
 TOP
 Abstract
 INTRODUCTION
 METHODS
 MAIN FEATURES AND COMMENTS
 EVALUATION OF THE EVIDENCE...
 References
 
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27 Marugame T, Sobue T, Satoh H, Komatsu S, Nishino Y, Nakatsuka H. Lung cancer death rates by smoking status: comparison of Three-Prefecture Cohort Study in Japan to the Cancer Prevention Study II in the USA. Cancer Sci 2005;96:120–6.[CrossRef][Medline]

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