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In an international comparison of recent mortality statistics among G7 countries, Japan had the longest average life expectancy, primarily due to remarkably low mortality rates from ischemic heart disease and cancer (particularly breast and prostate). As recently as the 1960s, life expectancy in Japan was the shortest among the G7 countries, owing to relatively high mortality from cerebrovascular disease—particularly intracerebral hemorrhage—and stomach cancer. Mortality rates for these diseases subsequently decreased significantly while the already low rates for ischemic heart disease and cancer also decreased, resulting in Japanese life expectancy becoming the longest. The low mortality rates from ischemic heart disease and cancer are thought to reflect the low prevalence of obesity in Japan; low intake of red meat, specifically saturated fatty acids; and high intakes of fish, specifically n-3 polyunsaturated fatty acids, plant foods such as soybeans, and nonsugar-sweetened beverages such as green tea. The decreasing mortality rates from cerebrovascular disease are thought to reflect the increases in animal foods, milk, and dairy products and consequently in saturated fatty acids and calcium, together with a decrease in salt intake which may have led to a decrease in blood pressure. This decrease in salt and highly salted foods also seems to account for the decrease in stomach cancer. The typical Japanese diet as characterized by plant food and fish as well as modest Westernized diet such as meat, milk and dairy products might be associated with longevity in Japan.

Because gastric cancer is still the most common cancer, its prevention is one of the most important aspects of Japan's cancer control strategy. Observations among Japanese immigrants in the USA and Brazil based on the geographic differences, the trend in cancer incidence with time, and the change in incidence patterns indicate that gastric cancer is closely associated with dietary factors, such as the intake of salt and salted food. In international and intra‐Japanese ecological studies, the average salt excretion level, estimated using randomly selected 24‐h urine samples in each population, was closely correlated with gastric cancer mortality. Several case–control and cohort studies, including the author's recent works, have shown that a higher intake of some traditional salt‐preserved food and salt per se, which was estimated using a validated food‐frequency questionnaire, was associated with a risk of gastric cancer. While salted food intake may increase the risk of Helicobacter pylori infection, it can also act synergistically to promote the development of gastric cancer. Based on substantial evidence about the association between salt and salted food intake and the risk of gastric cancer from ecological, case–control, and cohort studies conducted in Japan and other countries, as well as mechanistic plausibility, dietary modification involving less salt and salted food intake is a practical strategy with which to prevent gastric cancer. (Cancer Sci 2005; 96: 1–6)

Over the last 60 years, Japanese people have experienced a rapid and drastic change in lifestyle, including diet. Suspicions have been raised that so‐called ‘Westernization’, characterized by a high‐calorie diet and physical inactivity, is associated with increasing trends in the incidence of cancer of the colon, liver, pancreas, prostate, and breast, as well as type 2 diabetes. Epidemiological evidence from our prospective study, the Japan Public Health Center‐based Prospective (JPHC) study, and systematic literature reviews generally support the idea that factors related to diabetes or insulin resistance are associated with an increased risk of colon (mostly in men), liver, and pancreatic cancers. These cancers are inversely associated with physical activity and coffee consumption, which are known to decrease the risk of type 2 diabetes. The suggested mechanism of these effects is that insulin resistance and the resulting chronic hyperinsulinemia and increase in bioavailable insulin‐like growth factor 1 (IGF1) stimulate tumor growth. In contrast, associations with diabetes are less clear for cancer of the colon in women, and breast and prostate, which are known to be related to sex hormones. The effect of insulin resistance or body fat on sex‐hormone production and bioavailability may modify their carcinogenic effect differently from cancers of the colon in men, and liver and pancreas. In conclusion, there is substantial evidence to show that cancers of the colon, liver, and pancreas are associated with insulin resistance, and that these cancers can be prevented by increasing physical activity, and possibly coffee consumption. (Cancer Sci 2010; 101: 1073–1079)

PurposeThe present study aimed to examine the association between adherence to the Japanese diet and the subsequent risk of all-cause and cause-specific mortality using a large-scale cohort from settings all over Japan.MethodsWe analyzed data from a cohort study of 92,969 Japanese adults aged 45–74 years, covering 11 public health center areas nationwide. We collected dietary information using a validated 147-item food frequency questionnaire. Adherence to the Japanese diet consisting of eight components (high intake of rice, miso soup, seaweeds, pickles, green and yellow vegetables, fish, and green tea; low intake of beef and pork) was assessed using 8-item Japanese Diet Index (JDI8) score, with scores ranging from 0 to 8. The Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cause-specific mortality.ResultsDuring a median follow-up of 18.9 years, we documented 20,596 deaths. A higher JDI8 score was significantly associated with a lower risk for all-cause and cardiovascular disease (CVD) mortality. The multivariable-adjusted HR of all-cause and CVD mortality for the highest JDI8 score group (score of 6–8) versus the lowest JDI8 score group (score of 0–2) were 0.86 (95% CI 0.81–0.90, P trend < 0.001), and 0.89 (95% CI 0.80–0.99, P trend = 0.007), respectively.ConclusionsAdhering to the Japanese diet, as assessed by the JDI8, was associated with a decreased risk of all-cause and CVD mortality among adults living in multiple areas across Japan.

There are geographic and ethnic differences in the incidence of gastric cancer around the world as well as with its trends for each population over time. The incidence patterns observed among immigrants change according to where they live. All of these factors serve to indicate the close association of gastric cancer with modifiable factors such as diet. This review presents epidemiological evidence on the association between dietary factors and gastric cancer based on previous systematic reviews and subsequent updates. Infection with Helicobacter pylori is a strong and established risk factor of gastric cancer but is not a sufficient cause for its development. Substantial evidence from ecological, case-control, and cohort studies strongly suggests that the risk may be increased with a high intake of various traditional salt-preserved foods and salt per se and decreased with a high intake of fruit and vegetables, particularly fruit. However, it remains unclear which constituents in fruit and vegetables play a significant role in gastric cancer prevention. Among them, vitamin C is a plausible candidate supported by a relatively large body of epidemiological evidence. Consumption of green tea is possibly associated with a decreased risk of gastric cancer, although the protective effects have been, for the most part, identified in Japanese women, most of whom are nonsmokers. In contrast, processed meat and N-nitroso compounds may be positively associated with the risk of gastric cancer. In conclusion, dietary modification by reducing salt and salted food intake, as well as by increasing intake of fruit and vitamin C, represents a practical strategy to prevent gastric cancer.

Human height is a representative phenotype to elucidate genetic architecture. However, the majority of large studies have been performed in European population. To investigate the rare and low-frequency variants associated with height, we construct a reference panel ( N  = 3,541) for genotype imputation by integrating the whole-genome sequence data from 1,037 Japanese with that of the 1000 Genomes Project, and perform a genome-wide association study in 191,787 Japanese. We report 573 height-associated variants, including 22 rare and 42 low-frequency variants. These 64 variants explain 1.7% of the phenotypic variance. Furthermore, a gene-based analysis identifies two genes with multiple height-increasing rare and low-frequency nonsynonymous variants ( SLC27A3 and CYP26B1 ; P SKAT-O  < 2.5 × 10 −6 ). Our analysis shows a general tendency of the effect sizes of rare variants towards increasing height, which is contrary to findings among Europeans, suggesting that height-associated rare variants are under different selection pressure in Japanese and European populations. Thousands of genetic loci are known to associate with human height, but these are mainly based on studies in European ancestry populations. Here, Akiyama et al. construct a genotype reference panel for the Japanese population followed by GWAS and report 573 height associated variants in 191,787 Japanese.

Background: The mechanistic associations between obesity and risk of colorectal cancer (CRC) remain unclear. Here, using body mass index (BMI) as an obesity indicator, we decomposed the total effects of obesity on the risk of CRC into: (1) direct effects, which are possibly mediated by unmeasured or currently unknown factors; (2) indirect effects mediated by circulating leptin and adiponectin; and (3) indirect effects that are not mediated by circulating leptin and adiponectin but by hyperinsulinemia and chronic inflammation (assessed via circulating connecting peptide and C-reactive protein, respectively).Methods: We adopted a causal mediation framework, using data from a large prospective cohort study of 44,271 Japanese men.Results: BMI was not associated with the risk of CRC due to direct and indirect effects that were not mediated by circulating leptin and adiponectin. By contrast, individuals with BMIs of 25.0–27.4 kg/m2 (risk ratio, 1.29; 95% confidence interval, 0.98–1.69) and ≥27.5 kg/m2 (risk ratio, 1.28; 95% confidence interval, 0.98–1.68) had a higher risk of CRC due to indirect effects of circulating leptin and adiponectin.Conclusions: Our mediation analyses suggest that the association between BMI and CRC risk may be largely mediated by a pathway involving circulating leptin and adiponectin.

Background: Longitudinal epidemiological studies require both the periodic update of intake information via repeated dietary survey and the minimization of subject burden in responding to questionnaires. We developed a 66-item Food Frequency Questionnaire (short-FFQ) for the Japan Public Health Center-based prospective Study for the Next Generation (JPHC-NEXT) follow-up survey using major foods from the FFQ developed for the original JPHC Study. For the JPHC-NEXT baseline survey, we used a larger 172-item FFQ (long-FFQ), which was also derived from the JPHC-FFQ. We compared the validity of ranking individuals by levels of dietary consumption by these FFQs among residents of selected JPHC-NEXT study areas. Methods: From 2012 to 2013, 240 men and women aged 40-74 years from five areas in the JPHC-NEXT protocol were asked to respond to the long-FFQ and provide 12-day weighed food records (WFR) as reference; 228 also completed the short-FFQ. Spearman's correlation coefficients (CCs) between estimates from the FFQs and WFR were calculated and corrected for intra-individual variation of the WFR. Results: Median CC values for energy and 53 nutrients for the short-FFQ for men and women were 0.46 and 0.44, respectively. Respective values for the long-FFQ were 0.50 and 0.43. Compared with the long-FFQ, cross-classification into exact plus adjacent quintiles with the short-FFQ ranged from 68% to 91% in men and 58% to 85% in women. Conclusions: Similar to the long-FFQ, the short-FFQ provided reasonably valid measures for ranking middle-aged and elderly Japanese for many nutrients and food groups. The short-FFQ can be used in follow-up surveys in prospective cohort studies aimed at updating diet rank information.

Background: Although both a lower and a higher body mass index (BMI) are reportedly associated with head and neck cancer (HNC), reports from Asia are scarce. Moreover, evidence regarding the association between height and HNC is limited.Methods: We investigated associations between BMI, height, and the incidence of HNC among 102,668 participants (49,029 men and 53,639 women) aged 40–69 years in the Japan Public Health Center-based Prospective Study. We followed participants from 1990 to 2013. We conducted a Cox proportional hazards regression analysis, which included adjustment for potential confounders, such as smoking status. Baseline weight and height information were self-reported.Results: Over an average follow-up of 18.7 years, 311 HNC cases were newly diagnosed. Lower BMI was significantly associated with HNC, with hazard ratios (HR) of 2.75 (95% confidence interval [CI], 1.63–4.64) for <18.5 kg/m2 and 1.63 (95% CI, 1.15–2.30) for 18.5–20.9 kg/m2 compared to 23–24.9 kg/m2. Increased risk was suggested for higher BMI, with an HR of 1.30 (95% CI, 0.84–2.00) for ≥27.5 kg/m2. This trend was also observed in quadratic models. Results were similar among never-smokers. Meanwhile, only lower BMI showed a strong association with HNC risk among former and current smokers (HR 3.09; 95% CI, 1.54–6.20 for <18.5 kg/m2 compared to 23–24.9 kg/m2). Height showed no association with HNC.Conclusion: Lower BMI was significantly associated with HNC risk, while increased HNC risk was suggested in higher BMI among never-smokers. Among former and current smokers, only lower BMI was associated with HNC risk.