Yoshitaka Tsubono

Under- and overweight impact on mortality among middle-aged Japanese men and women: a 10-y follow-up of JPHC study cohort I.

OBJECTIVE: Although obesity is a major health problem in Western countries, its impact may differ in another culture. This paper examines the association between body mass index (BMI; kg/m2) and mortality in Japan, where the mortality profile and BMI distribution differ substantially from Western countries.DESIGN: The JPHC Study cohort I, a population-based prospective study in four public health center areas, started in 1990 and was followed-up to the end of 1999.SUBJECTS: A total of 19 500 men and 21 315 women aged 40–59 y who submitted their body weight and height and did not report any serious disease at baseline.MEASUREMENT: Risk of death by category of BMI.RESULTS: During 10 y of follow-up, 943 and 483 deaths were documented in the men and women, respectively. The association between BMI and all-cause mortality was U-shaped: compared with a category of 23.0–24.9, the statistically significant elevations in relative risk were observed in both under- and overweight categories (2.26 in 14.0–18.9, 1.57 in 19.0–20.9, 1.33 in 21.0–22.9 and 1.38 in 27.0–29.9, 1.97 in 30.0–39.9 in men, 1.94 in 14.0–18.9 and 1.91 in 30.0–39.9 in women) after adjustment for possible confounders and weight change. The U-shaped association did not change after excluding deaths occurring in the first 5 y of follow-up or even after excluding subjects who reported a weight loss of 5 kg or more since 20-y-old, or after stratifying subjects by smoking status.CONCLUSION: Both under- and overweight are important determinants of premature death among the Japanese population.

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.

Obesity and risk of cancer in Japan

We conducted a population‐based prospective cohort study in Japan to examine the relationship between body mass index (BMI) and the risk of incidence of any cancer and of cancer at individual sites. Body mass index was calculated from self‐administered body weight and height at baseline. Relative risks (RR) and 95% confidence intervals (CI) were calculated in multivariate proportional‐hazards models. Among 27,539 persons (15,054 women and 12,485 men) aged 40 years or older who were free of cancer at enrollment in 1984, 1,672 (668 women and 1,004 men) developed cancer during 9 years of follow‐up. In women, after adjustment for potential confounders, the RR of all cancers associated with different BMI, relative to a BMI of 18.5–24.9, were 1.04 (95% CI = 0.85–1.27) for BMI = 25.0–27.4, 1.29 (1.00–1.68) for BMI = 27.5–29.9 and 1.47 (1.06–2.05) for BMI ≥30.0 (p for trend = 0.007). Higher BMI was also significantly associated with higher risk of cancers of the colorectum, breast (postmenopausal), endometrium and gallbladder in women. In men, we observed significantly increased all‐cancer risk among only never‐smokers. Overweight and obesity could account for 4.5% (all subjects) or 6.2% (never‐smokers) of the risk of any cancer in women and −0.2% (all subjects) or 3.7% (never‐smokers) in men. The value for women was within the range among women reported from Western populations (3.2%–8.8%). Our data demonstrate that excess weight is a major cancer risk among Japanese women.

Coffee consumption and the risk of primary liver cancer: Pooled analysis of two prospective studies in Japan

Although case‐control studies suggested that coffee consumption is associated with a decreased risk of liver cancer, no prospective cohort study has been carried out. To examine the association between coffee consumption and the risk of liver cancer, we conducted a pooled analysis of data available from 2 cohort studies in Japan. A self‐administered questionnaire about the frequency of coffee consumption and other health habits was distributed to 22,404 subjects (10,588 men and 11,816 women) in Cohort 1 and 38,703 subjects (18,869 men and 19,834 women) in Cohort 2, aged 40 years or more, with no previous history of cancer. We identified 70 and 47 cases of liver cancer among the subjects in Cohort 1 (9 years of follow‐up with 170,640 person‐years) and Cohort 2 (7 years of follow‐up with 284,948 person‐years), respectively. We used Cox proportional hazards regression analysis to estimate the relative risk (RR) and 95% confidence interval (CI) of liver cancer incidence. After adjustment for potential confounders, the pooled RR (95% CI) of drinking coffee never, occasionally and 1 or more cups/day were 1.00 (Reference), 0.71 (0.46–1.09) and 0.58 (0.36–0.96), respectively (p for trend = 0.024). In the subgroup of subjects with a history of liver disease, we found a significant inverse association between coffee consumption and the risk of liver cancer. Our findings support the hypothesis that coffee consumption decreases the risk of liver cancer. Further studies to investigate the role of coffee in prevention of liver cancer among the high‐risk population are needed.

The increase of female breast cancer incidence in Japan: Emergence of birth cohort effect

During recent decades, breast cancer incidence has been increasing in Japan. According to the latest reports from several cancer registries in Japan, the breast has become the leading cancer site in female cancer incidence. To analyze the trend of breast cancer incidence in detail, we summarized female breast cancer incidence in Miyagi Prefecture, Japan during 1959–1997, and evaluated the period and cohort effect on breast cancer incidence using the age‐period‐cohort model. Age‐specific and age‐standardized rates have increased over successive calendar periods. Around 1980, an accelerated increase in these incidence rates took place. A full model including age, period and cohort was best fitted to the trend of incidence. In the model, the effects of period and cohort were statistically significant. The nonlinear effect for cohort indicates an increasing trend, beginning with the cohort in 1888–1897, and the nonlinear effect for period showed a clear increase in risk with calendar period. Furthermore, the full model including a linear component showed a steadily upward trend in the cohort effect. Based on our own epidemiologic studies previously conducted in Miyagi Prefecture, and other published reports, the cohort effect is likely to be related to the change in prevalence of women with risk factors such as low parity and insufficient breastfeeding. We believe that the emergence of the cohort effect is an important finding, although the period effect may also persist. The significant cohort effect may give a caution for continuous increase of breast cancer incidence in Japan.

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.

Screening for gastric cancer in Japan.

Abstract In Japan, mass screening for gastric cancer with photofluorography was initiated in 1960. At present, over 6 million people are screened annually. The sensitivity and specificity of photofluorography are 70%–90% and 80%–90%, respectively. The 5-year survival rate is 15%–30% better in screen-detected cancers than in symptom-diagnosed cases. Although no randomized controlled trials have been reported, cohort and case-control studies generally showed a decreased risk of mortality from gastric cancer in the screened subjects. The summary odds ratio (95% confidence interval) of three case-control studies for ever screened versus never screened subjects was 0.39 (0.29–0.52) for men and 0.50 (0.34–0.72) for women. Substantial evidence indicates that the Japanese screening program with photofluorography is effective in reducing the mortality from gastric cancer. The measurement of serum pepsinogens has recently drawn attention as an alternative to photofluorography, given its lower cost and simplicity. Some studies have suggested a comparable accuracy for the two methods. However, these investigations may have overestimated the relative sensitivity of serum pepsinogen testing compared with photofluorography, because serum pepsinogen testing was conducted as prevalent screening, while photofluorography was done as incident screening. Furthermore, no studies have directly examined whether the screening with serum pepsinogens reduced gastric cancer mortality. Therefore, at present, evidence is insufficient to determine the benefit of this program.

Green tea and the risk of breast cancer: pooled analysis of two prospective studies in Japan

In a pooled analysis of two prospective studies with 35 004 Japanese women, green-tea intake was not associated with a lower risk of breast cancer (222 cases), the multivariate relative risk for women drinking ⩾5 cups compared with <1 cup per day being 0.84 (95% confidence interval 0.57–1.24, Trend P=0.69).

Fibrotic focus in infiltrating ductal carcinoma of the breast: A significant histopathological prognostic parameter for predicting the long-term survival of the patients

The presence of fibratic fows (FF) in infiltrating ductal carcinoma (IDC) has been shown to be an important histological factor associated with high tumor aggressiveness, or early tumor recurrence or death. However, the clinicopathological significance of FF for predicting the long-term survival of the patients with IDC has not been fully investigated. In order to elucidate this aspect, we divided 140 IDCs with at least 10 years of follow up into tumors with FF and those without. IDC with FF showed significantly higher histologic grade (P=0.02), higher frequency of tumor necrosis (P=0.02), higher frequency of cases with more than three positive lymph node metastases (P=0.04), higher T classification (P=0.009), and higher pathological stage (P=0.0002) than those without FF. Relative risk (RR) of tumor recurrence and death was significantly higher in tumors with FF than in those without (RR=4.5, P < 0.00001 and RR=5.6, P < 0.00001, respectively). In cases of early stage cancer (stages I, IIA, and IIB), or in those with less than four lymph node metastases, IDCs with FF demonstrated a significantly higher risk than those without. Multivariate adjustments for other pathological factors did not change the RRs significantly. These results indicate that in long-term follow up the presence of FF is a significant prognostic parameter for IDC, and therefore strongly suggest that IDCs must be divided into those with and without FF.

Consumption of sodium and salted foods in relation to cancer and cardiovascular disease: the Japan Public Health Center-based Prospective Study.

BACKGROUND Although the influence of salt, per se, on the risk of cancer or cardiovascular disease (CVD) might differ from that of salt-preserved foods, few studies have simultaneously examined the effects of sodium and salted foods on the risk of either cancer or CVD. OBJECTIVE We simultaneously examined associations between sodium and salted food consumption and the risk of cancer and CVD. DESIGN During 1995-1998, a validated food-frequency questionnaire was administered to 77,500 men and women aged 45-74 y. During up to 598,763 person-years of follow-up until the end of 2004, 4476 cases of cancer and 2066 cases of CVD were identified. RESULTS Higher consumption of sodium was associated with a higher risk of CVD but not with the risk of total cancer: multivariate hazard ratios for the highest compared with lowest quintiles of intake were 1.19 (95% CI: 1.01, 1.40; P for trend: 0.06) for CVD and 1.04 (95% CI: 0.93, 1.16; P for trend: 0.63) for total cancer. Higher consumption of salted fish roe was associated with higher risk of total cancer, and higher consumption of cooking and table salt was associated with higher risk of CVD. Similar results were seen for the risk of gastric or colorectal cancer and stroke. CONCLUSIONS Sodium intake as a whole salt equivalent may not increase the risk of cancer but may increase that of CVD. In contrast, salted food intake may increase the risk of cancer. Our findings support the notion that sodium and salted foods have differential influences on the development of cancer and CVD.