Haruo Nakatsuka

Green tea and the risk of gastric cancer in Japan

BACKGROUND Although laboratory experiments and case-control studies have suggested that the consumption of green tea provides protection against gastric cancer, few prospective studies have been performed. METHODS In January 1984, a total of 26,311 residents in three municipalities of Miyagi Prefecture, in northern Japan (11,902 men and 14,409 women 40 years of age or older), completed a self-administered questionnaire that included questions about the frequency of consumption of green tea. During 199,748 person-years of follow-up, through December 1992, we identified 419 cases of gastric cancer (in 296 men and 123 women). We used Cox regression to estimate the relative risk of gastric cancer according to the consumption of green tea. RESULTS Green-tea consumption was not associated with the risk of gastric cancer. After adjustment for sex, age, presence or absence of a history of peptic ulcer smoking status, alcohol consumption, other dietary elements, and type of health insurance, the relative risks associated with drinking one or two, three or four, and five or more cups of green tea per day, as compared with less than one cup per day, were 1.1 (95 percent confidence interval, 0.8 to 1.6), 1.0 (95 percent confidence interval, 0.7 to 1.4), and 1.2 (95 percent confidence interval, 0.9 to 1.6), respectively (P for trend=0.13). The results were similar after the 117 cases of gastric cancer that were diagnosed in the first three years of follow-up had been excluded, with respective relative risks of 1.2 (95 percent confidence interval, 0.8 to 1.8) 1.0 (95 percent confidence interval, 0.7 to 1.5), and 1.4 (95 percent confidence interval, 1.0 to 1.9) (P for trend=0.07). CONCLUSIONS In a population-based, prospective cohort study in Japan, we found no association between green-tea consumption and the risk of gastric cancer.

Urban population exposure to lead and cadmium in east and south-east Asia

Information is still scarce for many Asian countries on general population exposure to two potentially toxic heavy metals of lead (Pb) and cadmium (Cd). The present review on publications from this study group is intended to provide an overview of the non-occupational exposure to Pb and Cd among general populations in east and south-east Asia. During the period of 1991-1998, surveys were conducted in four cities in south-east Asia, five cities in mainland China, and two cities each in Japan and Korea. Peripheral blood, morning spot urine and 24-h food duplicate samples were collected from 20-50 non-smoking adult women in each survey site. The samples were digested by heating in the presence of mineral acids, and then analyzed by inductively-coupled plasma mass spectrometry for the metals in blood (Pb-B and Cd-B), in urine (Pb-U and Cd-U), and in food duplicate (Pb-F and Cd-F). Measures were subjected to statistical analysis with an assumption of log-normal distribution. Pb-B, Pb-U and Pb-F levels varied substantially among the 11 urban sites; GM distributed in ranges of 32-65 microg/l for Pb-B, 2.1-7.5 microg/g cr (creatinine) for Pb-U, and 7-32 microg/day for Pb-F. The same was also the case for Cd exposure parameters, the distribution ranges being 0.5-1.8 microg/l for Cd-B, 1.2-3.1 microg/g cr for Cd-U, and 5-32 microg/day for Cd-F. It appeared that the exposure to Pb and Cd was highest in Kuala Lumpur, and Tokyo + Kyoto, respectively, and lowest in Tokyo + Kyoto and in Manila. Additional surveys in Japan showed that Pb exposure was even lower in rural areas than in Tokyo + Kyoto. When compared with the values reported in the literature, Pb exposure levels among Asian populations appear to be similar to the levels in Europe and in the United States, whereas Cd exposure seems to be higher in Asia than in Europe. The contribution of the dietary route in Pb absorption was variable and was inversely related to the extent of air pollution, whereas Cd uptake was almost exclusively via the dietary route with little contribution of the respiratory route.

Ambulatory blood pressure of adults in Ohasama, Japan.

We performed a cross-sectional study in a small town in northern Japan to evaluate the distribution, reference values, and daily variation in ambulatory blood pressure. A total of 705 subjects (229 men aged 61.3 +/- 13.4 years [mean +/- SD] and 476 women aged 57.5 +/- 13.3 years; 41.1% of the regional adult population, n = 1716), including those treated with antihypertensive drugs (n = 231, 66.5 +/- 9.5 years) as well as untreated subjects (n = 474, 55.0 +/- 13.5 years), participated in the study. Both ambulatory and screening blood pressures were measured in 659 subjects. Ambulatory blood pressure was measured with an automatic device (Colin ABPM-630). The 24-hour ambulatory blood pressure in the total population was 121.7 +/- 13.0/71.1 +/- 7.6 mm Hg (95th percentile value [95%] = 146/85 mm Hg). The corresponding value in the untreated subjects was 119.4 +/- 12.5/70.1 +/- 7.4 mm Hg (95% = 144/83 mm Hg). The 24-hour average ambulatory blood pressure was 118.0 +/- 11.1/69.4 +/- 6.8 mm Hg (95% = 139/81 mm Hg) in subjects identified as normotensive by their screening blood pressure (n = 448, 57.2 +/- 13.1 years) and 133.6 +/- 14.2/78.9 +/- 8.8 mm Hg in those identified as hypertensive by their screening blood pressure (n = 73, 63.1 +/- 10.6 years). Based on the mean+SD of the 24-hour ambulatory blood pressure in the normotensive subjects by their screening blood pressure (129/76 mm Hg), the 24-hour ambulatory blood pressures in 25 (34.2%) of these 73 hypertensive subjects by screening blood pressure were below this level. Nine (2%) of 448 normotensive subjects by screening blood pressure were above the mean+2 SDs (140/83 mm Hg) of the 24-hour ambulatory blood pressure in the normotensive group by screening blood pressure. Ambulatory and screening blood pressures increased with age. The age-dependent increase in ambulatory blood pressure was less apparent in men. The 24-hour average pulse rate decreased with age. The daily variation in ambulatory blood pressure (standard deviation) increased with age, whereas that of pulse rate decreased with age. Increases in blood pressure variation were observed in nighttime and daytime blood pressure values. The differences between day versus night ambulatory blood pressures decreased with age in men but not in women.(ABSTRACT TRUNCATED AT 400 WORDS)

Cadmium exposure of women in general populations in Japan during 1991–1997 compared with 1977–1981

Objectives: The Japanese people are known to have high environmental exposure to cadmium (Cd). The present survey was initiated to elucidate possible changes in the intensity of Cd exposure to the population by comparison of the present exposure level with the situation some 15 years ago. Methods: During 1991–1997, 24-h food-duplicate samples, peripheral blood specimens and morning spot urine samples were collected from 588 non smoking women from 27 survey sites in six regions, where food-duplicate and blood samples had also been obtained during 1977–1981 from 399 women. The samples were wet-ashed (after homogenization in the case of food-duplicates), and Cd in the wet-ashed samples was analyzed by inductively-coupled plasma mass spectrometry for Cd intake via foods (Cd-F), Cd concentration in blood (Cd-B) and Cd concentration in urine (Cd-U). The Cd-F and Cd-B were compared with the Cd-F and Cd-B obtained at the same sites in the 1977–1981 survey. Results: The exposure levels during 1991–1997 were such that Cd-F, Cd-B and Cd-Ucr (Cd–U after correction for creatinine concentration) were 25.5 μg/day, 1.90 μg/l and 4.39 μg/g creatinine. Comparison with the 1977–1981 survey results (i.e., 37.5 μg/day for Cd-F and 3.47 μg/l for Cd-B) showed that there were significant reductions (by 32 and 45%) in both parameters respectively during the last 15 years. The dietary route was an almost exclusive (i.e., 99% of the sum of dietary and respiratory uptake) route of Cd uptake, of which Cd in rice (11.7 μg/day) contributed about 40% of the total dietary intake. When compared among survey sites, inter-site variation in dietary Cd intake was primarily due to differences in the intake through boiled rice. Despite the recent reduction in Cd exposure, the current exposure level for Japanese people is still higher than the levels among other rice-dependent populations in Asia as well as in other parts of the world. Comparison was made between the present findings in general populations and observations among known Cd-pollution cases in Japan. Conclusions: Dietary uptake is an almost exclusive route of Cd exposure in the general Japanese population. Boiled rice is a strong determinant of variation in dietary Cd intake. Whereas there was a substantial reduction in Cd exposure among Japanese populations in the last 15 years, the current level is still high when compared internationally.

Cadmium and lead contents in rice and other cereal products in Japan in 1998-2000.

Cereals, especially rice, are a major source of cadmium (Cd) intake for general Japanese populations. In 1998-2000, rice (polished), bread (loaf), noodle and (wheat) flour samples (4113 samples in total) were collected in 63 cities all over Japan, and analyzed for Cd by inductively-coupled plasma mass spectrometry. Another pollutant element of lead (Pb) was determined in parallel. The grand geometric mean for Cd in polished raw (uncooked) rice was 50 ng/g, whereas it was 19 ng/g for flour. The value for Pb was 2-3 ng/g in rice and flour. Calculation for daily Cd intake via rice, taking advantage of the present findings on Cd contents in rice and wheat together with administrative area-specific daily consumptions of rice and wheat showed that Cd via rice is much more than Cd via wheat and that Cd via rice is highest in an area alongside the sea of Japan among the whole country, the observation being in agreement with the results from a previous food duplicate-based field survey.

Validation of a food-frequency questionnaire for cohort studies in rural Japan

OBJECTIVES To examine the validity and reproducibility of a self-administered food-frequency questionnaire (FFQ) used for two cohort studies in Japan. DESIGN Cross-sectional study. SETTING Two rural towns in the Miyagi Prefecture, in north-eastern Japan. SUBJECTS Fifty-five men and 58 women. RESULTS A 40-item FFQ was administered twice, 1 year apart. In the mean time, four 3-day diet records (DRs) were collected in four seasons within the year. We calculated daily consumption of total energy and 15 nutrients, 40 food items and nine food groups from the FFQs and the DRs. We computed Spearman correlation coefficients between the FFQs and the DRs. With adjustment for age, total energy and deattenuation for measurement error with the DRs, the correlation coefficients for nutrient intakes ranged from 0.25 to 0.58 in men and from 0.30 to 0.69 in women, with median of 0.43 and 0.43, respectively. Median (range) of the correlation coefficients was 0.35 (-0.30 to 0.72) in men and 0.34 (-0.06 to 0.75) in women for food items and 0.60 (-0.10 to 0.76) and 0.51 (0.28-0.70) for food groups, respectively. Median (range) of the correlation coefficients for the two FFQs administered 1 year apart was 0.49 (0.31-0.71) in men and 0.50 (0.40-0.64) in women for nutrients, 0.43 (0.14-0.76) and 0.45 (0.06-0.74) respectively for food items, and 0.50 (0.30-0.70) and 0.57 (0.39-0.66) respectively for food groups. Relatively higher agreement percentages for intakes of nutrients and food groups with high validity were obtained together with lower complete disagreement percentages. CONCLUSIONS The FFQ has a high reproducibility and a reasonably good validity, and is useful in assessing the usual intakes of nutrients, foods and food groups among a rural Japanese population.

An Association Between Long-Term Exposure to Ambient Air Pollution and Mortality From Lung Cancer and Respiratory Diseases in Japan

Background Evidence for a link between long-term exposure to air pollution and lung cancer is limited to Western populations. In this prospective cohort study, we examined this association in a Japanese population. Methods The study comprised 63 520 participants living in 6 areas in 3 Japanese prefectures who were enrolled between 1983 and 1985. Exposure to particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5), sulfur dioxide (SO2), and nitrogen dioxide (NO2) was assessed using data from monitoring stations located in or nearby each area. The Cox proportional hazards model was used to calculate the hazard ratios associated with the average concentrations of these air pollutants. Results The 10-year average concentrations of PM2.5, SO2, and NO2 before recruitment (1974–1983) were 16.8 to 41.9 µg/m3, 2.4 to 19.0 ppb, and 1.2 to 33.7 ppb, respectively (inter-area range). During an average follow-up of 8.7 years, there were 6687 deaths, including 518 deaths from lung cancer. The hazard ratios for lung cancer mortality associated with a 10-unit increase in PM2.5 (µg/m3), SO2 (ppb), and NO2 (ppb) were 1.24 (95% confidence interval: 1.12–1.37), 1.26 (1.07–1.48), and 1.17 (1.10–1.26), respectively, after adjustment for tobacco smoking and other confounding factors. In addition, a significant increase in risk was observed for male smokers and female never smokers. Respiratory diseases, particularly pneumonia, were also significantly associated with all the air pollutants. Conclusions Long-term exposure to air pollution is associated with lung cancer and respiratory diseases in Japan.

Mutual metabolic suppression between benzene and toluene in man

SummaryThe exposure intensity during a shift and the metabolite levels in the shift-end urine were examined in male workers exposed to either benzene (65 subjects; the benzene group), toluene (35 subjects; the toluene group), or a mixture of both (55 subjects; the mixture group). In addition, 35 non-exposed male workers (the control group) were similarly examined for urinary metabolites to define background levels. A linear relationship was established between the intensity of solvent exposure and the corresponding urinary metabolite levels (i.e. phenol, catechol and quinol from benzene, and hippuric acid and o-cresol from toluene) in each case when one of the three exposed groups was combined with the control group for calculation. Comparison of regression lines in combination with regression analysis disclosed that urinary levels of phenol and quinol (but not catechol) were lower in the mixture group than in the benzene group when the intensities of exposure to benzene were comparable, indicating that the biotransformation of benzene to phenolic compounds (excluding catechol) in man is suppressed by co-exposure to toluene. Conversely, metabolism of toluene to hippuric acid was suppressed by benzene co-exposure. Conversion of toluene to o-cresol was also reduced by benzene, but to a lesser extent. The significance of the present findings on the mutual suppression of metabolism between benzene and toluene is discussed in relation to solvent toxicology and biological monitoring of exposure to the solvents.

Urinary t,t-muconic acid as an indicator of exposure to benzene

A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non-corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene.

Cadmium and lead contents of cigarettes produced in various areas of the world

Cigarette packs, 331 in total, were purchased in 20 areas including nine in Asia between 1982 and 1984, and analyzed for cadmium and lead by flameless atomic absorption spectrophotometry after wet digestion with nitric, sulfuric and perchloric acids. The arithmetic mean (geometric mean in parentheses) for Cd was 1.15 (1.06) micrograms/cigarette or 1.45 (1.31) micrograms/g, and the values for Pb were 1.70 (1.31) micrograms/cigarette or 1.76 (1.67) micrograms/g. The Cd content of cigarettes was distributed over a wide range from 0.29 to 3.38 micrograms/g, and the range was even wider for Pb, 0.46 to 43.66 micrograms/g. The mean values varied markedly depending on the area of production. It was not possible, however, to obtain any evidence to suggest that the differences in Cd and Pb contents are related to the area of production or the extent of industrial development of the area.