Reproducibility and dietary correlates of plasma polyphenols in the JPHC-NEXT Protocol Area study.

BACKGROUND: In recent years, an increasing number of epidemiological studies have suggested a role of polyphenols in the prevention of chronic diseases. Prospective cohort studies have typically measured polyphenol concentrations in a single blood sample and the reproducibility of plasma polyphenol measurements is largely unknown. OBJECTIVE: We evaluated the reproducibility of 35 plasma polyphenols collected at an interval of 1-year. We also examined correlations of these polyphenols with food group intakes calculated from weighed food records (WFR) and food frequency questionnaire (FFQ). METHODS: The study included 227 middle-aged participants from the JPHC-NEXT Protocol Area in Japan. We measured 35 polyphenols in plasma collected at two points 1-year apart. Food group intakes were calculated from 12-day WFR and FFQ. For the reproducibility analysis, the intraclass correlation coefficient (ICC) of 35 polyphenol concentrations were examined between the two points. Pearson's partial correlations was used to assess the correlation between polyphenols and food groups. RESULTS: Moderate- to high ICCs were observed for tea-originated polyphenols such as gallic acid, quercetin, epigallocatechin, and kaempferol - and coffee-derived polyphenols, such as caffeic acid, and ferulic acid. For the dietary analyses, moderate correlations were observed for non-alcoholic beverages intake and epigallocatechin, epicatechin, catechin, and gallic acid. For green tea, higher correlations were observed with these polyphenols. CONCLUSION: Plasma concentrations of tea and coffee-related polyphenols, except for catechin, had good reproducibility over a 1-year period. The correlations between intake of non-alcoholic beverages, particularly green tea, and tea polyphenols, indicated moderate- to high correlations.

Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).

Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country-specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal-cell carcinoma (BCC): n = 8711; squamous-cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow-up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1-4.9 g/day: HR = 1.44, 95% CI = 1.17-1.77; Ptrend  = .001), BCC (HR = 1.12, 95% CI = 1.01-1.23; Ptrend  = .04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; Ptrend  = .17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; Ptrend  = .13; BCC: HR = 1.08, 95% CI = 1.00-1.17, Ptrend  = .03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, Ptrend  = .13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08-1.99; Ptrend  = .0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31; Ptrend  = .14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11-1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer.

Prediagnostic plasma polyphenol concentrations and colon cancer risk: The JPHC nested case-control study.

BACKGROUND & AIMS: Epidemiological studies that assessed the associations between dietary polyphenol intakes and colon cancer risk have reported largely null results, possibly due to measurement error associated with dietary assessment. We adopted an objective approach by measuring prediagnostic plasma concentrations of 35 polyphenols and assessing associations with colon cancer risk. METHODS: We conducted a nested-case control study within the Japan Public Health Center-based prospective study (JPHC Study) utilizing plasma samples collected at the time of a five-year follow-up survey between 1995 and 1999. We identified colon cancer cases who developed cancer during the follow-up from the time of blood collection. Controls were matched by age, sex, area code, population size of the area, season of blood collection, year of blood collection, and duration of fasting time before the blood collection. Prediagnostic concentrations of 35 polyphenols from 375 incident colon cancer cases (followed until 2012) and 710 matched controls were measured by tandem mass spectrometry coupled with ultra-high-pressure liquid chromatography. We used multivariable conditional logistic regression models adjusted for established colon cancer risk factors to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In sexes combined log2-transformed multivariable models, circulating levels of 3,4-dihydroxyphenylpropionic acid (P = 0.02), ferulic acid (P = 0.02), and caffeic acid (P = 0.03) were inversely, and 3-hydroxybenzoic acid (P = 0.03) was positively, associated with colon cancer risk. For men only, circulating levels of 3,4-dihydroxyphenylpropionic acid was inversely, and 3,5-dihydroxyphenylpropionic acid, gallic acid, (+)-epigallocatechin, 3-hydroxybenzoic acid, and epicatechin were positively, associated with colon cancer risk. In women, plasma caffeic acid and ferulic acid concentration were inversely associated with colon cancer risk. However, all these associations were nonsignificant after adjustment for multiple comparisons. The remaining polyphenols were not associated with colon cancer risk. CONCLUSION: Coffee-derived 3,4-dihydroxyphenylpropionic acid, ferulic acid, and caffeic acid concentrations were inversely associated with colon cancer risk although the association were nonsignificant after adjustment for multiple comparisons. These results support a possible role of coffee polyphenols in preventing colorectal cancer.

Circulating Sex Hormone Levels and Colon Cancer Risk in Men: A Nested Case-Control Study and Meta-Analysis.

BACKGROUND: Endogenous sex hormones may contribute to higher colorectal cancer incidence rates in men compared with women, but despite an increased number of studies, clear evidence is lacking. METHODS: We conducted a comprehensive nested case-control study of circulating concentrations of sex hormones, sex hormone precursors, and sex hormone binding globulin (SHBG) in relation to subsequent colon cancer risk in European men. Concentrations were measured using liquid LC/MS-MS in prospectively collected plasma samples from 690 cases and 690 matched controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). In addition, we conducted a meta-analysis of previous studies on men. RESULTS: Circulating levels of testosterone (OR, 0.68; 95% CI, 0.51-0.89) and SHBG (OR, 0.77; 95% CI, 0.62-0.96) were inversely associated with colon cancer risk. For free testosterone, there was a nonsignificant inverse association (OR, 0.83; 95% CI, 0.58-1.18). In a dose-response meta-analysis of endogenous sex hormone levels, inverse associations with colorectal/colon cancer risk were found for testosterone [relative risks (RR) per 100 ng/dL = 0.98; 95% CI, 0.96-1.00; I2 = 22%] and free testosterone (RR per 1 ng/dL = 0.98; 95% CI, 0.95-1.00; I2 = 0%). CONCLUSIONS: Our results provide suggestive evidence for the association between testosterone, SHBG, and male colon cancer development. IMPACT: Additional support for the involvement of sex hormones in male colon cancer.

Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis.

Background: Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results. Methods: We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided. Results: In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1 = 1.33 [95% confidence interval = 0.89 to 1.97], P trend = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk. Conclusion: Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.

Validity of a food frequency questionnaire for the estimation of total polyphenol intake estimates and its major food sources in the Japanese population: the JPHC FFQ Validation Study.

We examine the validity and reproducibility of a food frequency questionnaire (FFQ) in a subsample of participants in the Japan Public Health Center-based Prospective Cohort Study using a database of polyphenol-containing foods commonly consumed in the Japanese population. Participants of the validation study were recruited from two different cohorts. In Cohort I, 215 participants completed a 28-d dietary record (DR) and the FFQ, and in Cohort II, 350 participants completed DRs and the FFQ. The total polyphenol intake estimated from the 28-d DR and FFQ were log-transformed and adjusted for energy intake by the residual method. Spearman correlation coefficients (CCs) between estimates from the FFQ and 28-d DR as well as two FFQs administered at a 1-year interval were computed. Median intakes of dietary polyphenols calculated from the DRs were 1172 mg/d for men and 1024 mg/d for women in Cohort I, and 1061 mg/d for men and 942 mg/d for women in Cohort II. The de-attenuated CCs for polyphenol intake between the DR and FFQ were 0⋅47 for men and 0⋅37 for women in Cohort I and 0⋅44 for men and 0⋅50 for women in Cohort II. Non-alcoholic beverages were the main contributor to total polyphenol intake in both men and women, accounting for 50 % of total polyphenol intake regardless of cohort and gender, followed by alcoholic beverages and seasoning and spices in men, and seasoning and spices, fruits and other vegetables in women. The present study showed that this FFQ had moderate validity and reproducibility and is suitable for use in future epidemiological studies.

Circulating Levels of Testosterone, Sex Hormone Binding Globulin and Colorectal Cancer Risk: Observational and Mendelian Randomization Analyses.

BACKGROUND: Epidemiologic studies evaluating associations between sex steroid hormones and colorectal cancer risk have yielded inconsistent results. To elucidate the role of circulating levels of testosterone, and sex hormone-binding globulin (SHBG) in colorectal cancer risk, we conducted observational and Mendelian randomization (MR) analyses. METHODS: The observational analyses included 333,530 participants enrolled in the UK Biobank with testosterone and SHBG measured. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models. For MR analyses, genetic variants robustly associated with hormone levels were identified and their association with colorectal cancer (42,866 cases/42,752 controls) was examined using two-sample MR. RESULTS: In the observational analysis, there was little evidence that circulating levels of total testosterone were associated with colorectal cancer risk; the MR analyses showed a greater risk for women (OR per 1-SD = 1.09; 95% CI, 1.01-1.17), although pleiotropy may have biased this result. Higher SHBG concentrations were associated with greater colorectal cancer risk for women (HR per 1-SD = 1.16; 95% CI, 1.05-1.29), but was unsupported by the MR analysis. There was little evidence of associations between free testosterone and colorectal cancer in observational and MR analyses. CONCLUSIONS: Circulating concentrations of sex hormones are unlikely to be causally associated with colorectal cancer. Additional experimental studies are required to better understand the possible role of androgens in colorectal cancer development. IMPACT: Our results from large-scale analyses provide little evidence for sex hormone pathways playing a causal role in colorectal cancer development.See related commentary by Hang and Shen, p. 1302.

Fermented soy products intake and risk of cardiovascular disease and total cancer incidence: The Japan Public Health Center-based Prospective study.

BACKGROUND/OBJECTIVES: The association of fermented soy products, separately from total soy products, with cardiovascular disease (CVD) and total cancer has not been reported. We examined this association in a population-based prospective cohort study in Japan. SUBJECTS/METHODS: We studied 79,648 participants (42,788 women; 36,860 men) aged 45-74 years without a history of cancer, myocardial infarction, or stroke. Participants completed a food frequency questionnaire (1995-1998) and were followed to 2009-2012. Cox proportional hazards regression analysis was used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) of incidence of CVD and total cancer according to quartiles of total soy products, nonfermented soy products, fermented soy products, miso soup, natto, total isoflavones from soy products, isoflavones from nonfermented soy products, and isoflavones from fermented soy products. RESULTS: In women, we observed a significant inverse association between fermented soy product intake and the risk of CVD (multivariate HR in the highest compared with the lowest quartile of fermented soy product intake: 0.80; 95% CI: 0.68, 0.95; P for trend = 0.010), and also found significant inverse associations for natto and isoflavones among fermented soy products. In site-specific analysis, we observed a similar, significant inverse association between fermented soy product intake and the risk of stroke in women. We found no significant association between any soy product and risk of CVD in men or total cancer in both sexes. CONCLUSIONS: Intake of fermented soy products such as natto was inversely associated with the risk of CVD in women.

Comparison between the impact of fermented and unfermented soy intake on the risk of liver cancer: the JPHC Study.

PURPOSE: The aim of this study was to compare the impact of fermented and unfermented soy intake, based on the following soy-derived products: tofu, soymilk, natto, and miso, on the risk of liver cancer among Japanese adults. METHODS: 75,089 Participants of the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from the time of the 5-year follow-up questionnaire until the end of 2012-2013. Subjects with available data on hepatitis B virus (HBV) and hepatitis C virus (HCV) infection status from blood samples (n = 14,016) and those who were anti-HCV antibody (anti-HCV) or hepatitis B virus antigen (HBsAg) positive (n = 1033) were also analyzed separately. Cox proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During 1,145,453 person-years, 534 newly diagnosed cases of liver cancer were identified in the JPHC Study. For miso intake among men, the multivariate-adjusted highest versus lowest quartile HR was 0.65 (95% CI, 0.48-0.89); p for trend = 0.006. Results were similar in those who were anti-HCV or HBsAg positive, 0.24 (0.08-0.70); p for trend = 0.004 highest versus lowest tertile. For the sub-analysis among only participants with known hepatitis infection status and HCV and HBsAg adjustment, a similar association was observed. In the multivariate complete cohort analysis, among women, the highest intake of fried tofu was inversely associated with the risk of liver cancer, HR = 0.45 (0.26-0.80); p for trend = 0.014. CONCLUSIONS: We observed no association between total soy intake, fermented and unfermented, and risk of liver cancer, and only an inverse association between miso intake and liver cancer among men.

Meat subtypes and colorectal cancer risk: A pooled analysis of 6 cohort studies in Japan.

Red meat and processed meat have been suggested to increase risk of colorectal cancer (CRC), especially colon cancer. However, it remains unclear whether these associations differ according to meat subtypes or colon subsites. The present study addressed this issue by undertaking a pooled analysis of large population-based cohort studies in Japan: 5 studies comprising 232 403 participants (5694 CRC cases) for analysis based on frequency of meat intake, and 2 studies comprising 123 635 participants (3550 CRC cases) for analysis based on intake quantity. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model and then pooled using the random effect model. Comparing the highest vs lowest quartile, beef intake was associated with an increased risk of colon cancer in women (pooled HR 1.20; 95% CI, 1.01-1.44) and distal colon cancer (DCC) risk in men (pooled HR 1.30; 95% CI, 1.05-1.61). Frequent intake of pork was associated with an increased risk of distal colon cancer in women (pooled HR 1.44; 95% CI, 1.10-1.87) for "3 times/wk or more" vs "less than 1 time/wk". Frequent intake of processed red meat was associated with an increased risk of colon cancer in women (pooled HR 1.39; 95% CI, 0.97-2.00; P trend = .04) for "almost every day" vs "less than 1 time/wk". No association was observed for chicken consumption. The present findings support that intake of beef, pork (women only), and processed red meat (women only) might be associated with a higher risk of colon (distal colon) cancer in Japanese.

Circulating sex hormone levels and colorectal cancer risk in Japanese postmenopausal women: The JPHC nested case-control study.

Previous epidemiological studies evaluated endogenous sex hormone levels and colorectal cancer (CRC) risk have yielded inconsistent results. Also, it is unknown if consumption of dietary isoflavones may influence the endogenous sex hormones and CRC relationships. We conducted a nested case-control study within the JPHC Study Cohort II wherein 11,644 women provided blood samples at the 5-year follow-up survey. We selected two matched controls for each case from the cohort (185 CRC cases and 361 controls). Multivariable conditional logistic regression was used to estimate odds ratios (ORs), 95% confidence intervals (CIs) for the association between circulating sex hormone levels and CRC risk. Comparing extreme tertiles, circulating testosterone levels were positively associated with CRC risk (OR = 2.10, 95% CI = 1.11-3.99, p for trend = 0.03). Levels of estradiol, SHBG, and progesterone were not associated with CRC risk. In a subgroup analysis by dietary isoflavone intake, SHBG levels were positively associated with CRC risk among those with low total isoflavone intake (p for trend = 0.03), with a statistically nonsignificant inverse association among those with high total isoflavone intake (p for trend = 0.22; p for interaction = 0.002). Endogenous levels of testosterone were positively associated with CRC among postmenopausal women. The association of endogenous SHBG with CRC development may be altered by the level of dietary isoflavone intake.

Cruciferous vegetable intake and mortality in middle-aged adults: A prospective cohort study.

BACKGROUND & AIMS: Cruciferous vegetables contain isothiocyanates, which effectively reduce inflammation and oxidative stress related to chronic diseases, inhibit the bioactivation of procarcinogens, and enhance the excretion of carcinogens. However, at present, no large cohort studies have investigated the effect of cruciferous vegetable on mortality. We aimed to examine the association between cruciferous vegetable intake and all-cause mortality, namely cancer, heart disease, cerebrovascular disease, and injuries, in a large cohort study conducted between 1990 and 1993, in Japan. METHODS: The analysis included 88,184 participants (age: 45-74 years) with no history of cancer, myocardial infarction, and stroke. Participants were tracked for a median of 16.9 years, during which 15,349 deaths were occurred. The association between cruciferous vegetable intake and risk of all-cause and cause-specific mortality was determined by Cox proportional hazard regression analysis to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), after adjustment for potential confounding factors. RESULTS: An inverse association was found between cruciferous vegetable intake and total mortality in both gender. HRs (95% CI) for all-cause mortality in the highest compared to the lowest quintile were 0.86 (0.80, 0.93) for men (P = 0.0002 for trend) and 0.89 (0.81, 0.98) for women (P = 0.03 for trend). Cruciferous vegetable intake was associated with lower cancer mortality in men, as well as with heart disease-, cerebrovascular disease-, and injury-related mortality in women. CONCLUSIONS: This prospective study suggests that a higher cruciferous vegetables intake is associated with reduced risk of all-cause mortality.

Cruciferous vegetable intake and colorectal cancer risk: Japan public health center-based prospective study.

We aimed to assess the association between cruciferous vegetable intake and colorectal cancer (CRC) development among Japanese adults aged between 45 and 74 years in the Japan Public Health Center-based Prospective Study. During 1 325 853 person-years of follow-up, 2612 CRC cases were identified. The association of cruciferous vegetable intake with CRC risk was assessed using a Cox proportional hazard regression model to compute hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. No significant association was observed between the highest cruciferous vegetable intake quartile (compared with the lowest) and CRC risk in men (multivariate HRs: 1.08; 95% CI: 0.91, 1.29) and women (multivariate HRs: 0.99; 95% CI: 0.80, 1.22) and its subsites. Women showed a marginal negative association between cruciferous vegetable intake and the risk of colon cancer (CC) after excluding participants who developed CC in the first 3 years of follow-up (P for trend = 0.08); a positive association was found with proximal CC in men. Cruciferous vegetable intake does not have a significant association with CRC risk in the Japanese general population.

Cruciferous Vegetable Intake Is Inversely Associated with Lung Cancer Risk among Current Nonsmoking Men in the Japan Public Health Center (JPHC) Study.

Background: Cruciferous vegetables, a rich source of isothiocyanates, have been reported to lower the risk of several types of cancer, including lung cancer. However, evidence from prospective observations of populations with a relatively high intake of cruciferous vegetables is sparse.Objective: We investigated the association between cruciferous vegetable intake and lung cancer risk in a large-scale population-based prospective study in Japan.Methods: We studied 82,330 participants (38,663 men; 43,667 women) aged 45-74 y without a past history of cancer. Participants were asked to respond to a validated questionnaire that included 138 food items. The association between cruciferous vegetable intake and lung cancer incidence was assessed with the use of Cox proportional hazard regression analysis to estimate HRs and 95% CIs (with adjustments for potential confounding factors).Results: After 14.9 y of follow-up, a total of 1499 participants (1087 men; 412 women) were diagnosed with lung cancer. After deleting early-diagnosed cancer and adjusting for confounding factors, we observed a nonsignificant inverse trend between cruciferous vegetable intake and lung cancer risk in men in the highest compared with the lowest quartiles (multivariate HR: 0.85; 95% CI: 0.69, 1.06; P-trend = 0.13). Stratified analysis by smoking status revealed a significant inverse association between cruciferous vegetable intake and lung cancer risk among those who were never smokers and those who were past smokers after deleting lung cancer cases in the first 3 y of follow-up [multivariate HR for never smokers: 0.49 (95% CI: 0.27, 0.87; P-trend = 0.04); multivariate HR for past smokers: 0.59 (95% CI: 0.35, 0.99; P-trend = 0.10)]. No association was noted in men who were current smokers and women who were never smokers.Conclusion: This study suggests that cruciferous vegetable intake may be associated with a reduction in lung cancer risk among men who are currently nonsmokers.

Industry Speed Bumps on Local Tobacco Control in Japan? The Case of Hyogo.

BACKGROUND: Despite being a signatory since 2004, Japan has not yet fully implemented Article 8 of the World Health Organization's Framework Convention on Tobacco Control regarding 100% protection against exposure to second-hand smoke (SHS). The Japanese government still recognizes designated smoking rooms (DSRs) in public space as a valid control measure. Furthermore, subnational initiatives for tobacco control in Japan are of limited effectiveness. Through an analysis of the Hyogo initiative in 2012, we identified key barriers to the achievement of a smoke-free environment. METHODS: Using a descriptive case-study approach, we analyzed the smoke-free policy development process. The information was obtained from meeting minutes and other gray literature, such as public records, well as key informant interviews. RESULTS: Hyogo Prefecture established a committee to propose measures against SHS, and most committee members agreed with establishing completely smoke-free environments. However, the hospitality sector representatives opposed regulation, and tobacco companies were allowed to make a presentation to the committee. Further, political power shifted against completely smoke-free environments in the context of upcoming local elections, which was an obvious barrier to effective regulation. Throughout the approving process, advocacy by civil society for stronger regulation was weak. Eventually, the ordinance approved by the Prefectural Assembly was even weaker than the committee proposal and included wide exemptions. CONCLUSIONS: The analysis of Hyogo's SHS control initiative shed light on three factors that present challenges to implementing tobacco control regulations in Japan, from which other countries can also draw lessons: incomplete national legislation, the weakness of advocacy by the civil society, and the interference of the tobacco industry.

Designated smoking areas in streets where outdoor smoking is banned.

Although Japan has been a signatory to the Framework Convention on Tobacco Control since 2004, progress in translating the recommendations into national policy has been limited. Globally, outdoor smoking bans cover outdoor dining areas, beaches, public parks, schools, etc. In Japan, most of existing outdoor smoking bans allow designated smoking areas (DSAs) in the no-smoking zones, thus limiting protection from second-hand smoke (SHS). We examined the impact of DSAs on air quality in the areas of Kobe City where such ordinance is in force. Air quality measurements were conducted near two DSAs in August 2012 by using personal aerosol monitors. Three measurements were performed, each for 15 minutes, by four investigators: a line-up measurement, a vertical and horizontal measurement, and a circle measurement. In the line-up measurement, over 150 µg/m³ of PM2.5 was detected by the monitor four metres from the ashtray, gradually reducing as the distance increased. In the vertical and horizontal measurement, 80-110 µg/m³ of PM2.5 was detected at 4, 11, 18 and 25 metres. In the circle measurement, similar concentrations of PM2.5 were detected at all testing points (mean concentration 94 µg/m³). The study indicates that DSAs are sources of SHS in zones where a street smoking ban is in force, since SHS spreads widely, both vertically and horizontally. Street smoking bans that permit DSAs strongly limit protection from SHS and should be eliminated if protection against SHS is to be effective where such bans are in force.