Search

Cigarette smoke contains many oxidants and free radicals which may affect the association between vegetable and fruit intake and colorectal cancer (CRC) risk. However, this relationship remains unclear.This study aimed to investigate the associations between vegetable and fruit intake and CRC risk by smoking status.The Japan Public Health Center-based Prospective Study is a population-based prospective cohort study. Participants completed a self-administered questionnaire in 1995-1999 (baseline survey) and were followed through to 2013. At the baseline survey, 89,283 residents (41,797 men and 47,486 women) aged 45-74 years were included. Participants were asked about their lifestyle and dietary habits. To investigate the association of vegetable and fruit intake with risk of CRC, Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We analyzed the relationship between vegetable and fruit intake and CRC risk stratified by sex and smoking status.During follow-up, 2261 participants were diagnosed with CRC. Overall, vegetable and fruit intake were not associated with CRC risk in either sex. When stratified by sex and smoking status, CRC risk among male never smokers was inversely associated with intake of vegetables and fruit combined (HR: 0.72; 95% CI: 0.53, 0.98; highest vs lowest quartile p trend = 0.01) and fruit alone (HR: 0.62; 95% CI: 0.45, 0.86; p trend 0.01).Cigarette smoking may affect the association between vegetable and fruit intake and CRC risk among men.

Evidence from several cohorts has suggested that a higher intake of isoflavone is associated with lower risk of lung cancer in never smokers, but the association has not been investigated by histologic type of lung cancer. Adenocarcinoma is a common histologic type found in never smokers. We hypothesized that a higher intake of isoflavone is associated with a lower risk of lung adenocarcinoma among never smokers. Here, we examined the associations of isoflavone and soy food intake with lung cancer and its histologic types in never smokers.We performed a pooled analysis using data from the Japan Public Health Center-based Prospective Study, Shanghai Women's Health Study and Shanghai Men's Study with 147,296 never smokers aged 40-74 years with no history of cancer. During 1,990,040 person-years of follow-up, 1247 lung cancer cases were documented. Dietary isoflavone and soy food intake were assessed using a food-frequency questionnaire. Multivariable Cox proportional hazards models assessed the associations between isoflavone and soy intake with incidence of lung cancer by histologic type.A higher intake of dietary isoflavone and soy food were associated with reduced risk of lung adenocarcinoma. The multivariable hazard ratios (HRs) (95% CI) of risk of lung adenocarcinoma for the highest versus lowest intakes of isoflavone and soy food were 0.74 (0.60-0.92) and 0.78 (0.63-0.96), respectively. The multivariable HRs of risk of lung adenocarcinoma associated with each 10 mg/day increase in isoflavone and each 50 g/day increase in soy food intake were 0.81 (0.70-0.94) and 0.84 (0.73-0.96), respectively.Higher intake of isoflavone and soy food was associated with lower risk of lung adenocarcinoma in never smokers.

Observational studies suggest that abnormal glucose metabolism and insulin resistance contribute to colorectal cancer; however, the causal association remains unknown, particularly in Asian populations. A two-sample Mendelian randomisation analysis was performed to determine the causal association between genetic variants associated with elevated fasting glucose, haemoglobin A1c (HbA1c), and fasting C-peptide and colorectal cancer risk. In the single nucleotide polymorphism (SNP)-exposure analysis, we meta-analysed study-level genome-wide associations of fasting glucose (~ 17,289 individuals), HbA1c (~ 52,802 individuals), and fasting C-peptide (1,666 individuals) levels from the Japanese Consortium of Genetic Epidemiology studies. The odds ratios of colorectal cancer were 1.01 (95% confidence interval [CI], 0.99–1.04, P = 0.34) for fasting glucose (per 1 mg/dL increment), 1.02 (95% CI, 0.60–1.73, P = 0.95) for HbA1c (per 1% increment), and 1.47 (95% CI, 0.97–2.24, P = 0.06) for fasting C-peptide (per 1 log increment). Sensitivity analyses, including Mendelian randomisation-Egger and weighted-median approaches, revealed no significant association between glycaemic characteristics and colorectal cancer (P > 0.20). In this study, genetically predicted glycaemic characteristics were not significantly related to colorectal cancer risk. The potential association between insulin resistance and colorectal cancer should be validated in further studies.

Exposure to certain chemicals in the environment may contribute to the risk of developing cancer. Although cancer risk from environmental chemical exposure among general populations is considered low compared to that in occupational settings, many people may nevertheless be chronically exposed to relatively low levels of environmental chemicals which vary by such various factors as residential area, lifestyle, and dietary habits. It is therefore necessary to assess population-specific exposure levels and examine their association with cancer risk. Here, we reviewed epidemiological evidence on cancer risk and exposure to dichlorodiphenyltrichloroethane (DDT), hexachlorocyclohexane (HCH), polychlorinated biphenyls (PCBs), per- and polyfluoroalkyl substances (PFASs), cadmium, arsenic, and acrylamide. Japanese are widely exposed to these chemicals, mainly through the diet, and an association with increased cancer risk is suspected. Epidemiological evidence from Japanese studies to date does not support a positive association between blood concentrations of DDT, HCH, PCBs, and PFASs and risk of breast or prostate cancer. We established assessment methods for dietary intake of cadmium, arsenic, and acrylamide using a food frequency questionnaire. Overall, dietary intakes of cadmium, arsenic, and acrylamide were not significantly associated with increased risk of total cancer and major cancer sites in the Japan Public Health Center-based Prospective Study. However, statistically significant positive associations were observed between dietary cadmium intake and risk of estrogen receptor-positive breast cancer among postmenopausal women, and dietary arsenic intake and risk of lung cancer among male smokers. In addition, studies using biomarkers as exposure assessment revealed statistically significant positive associations between urinary cadmium concentration and risk of breast cancer, and between ratio of hemoglobin adducts of acrylamide and glycidamide and risk of breast cancer. Epidemiological studies of general populations in Japan are limited and further evidence is required. In particular, studies of the association of organochlorine and organofluorine compounds with risk of cancer sites other than breast and prostate cancer are warranted, as are large prospective studies of the association between biomarkers of exposure and risk of cancer.

Background Some studies have investigated the relation between dairy products and mortality, but with inconsistent results. Objective We examined the association between the consumption of dairy products and the risk of all-cause, cancer-related, and cardiovascular disease (CVD)-related mortality. Methods From the Japan Public Health Center-based Prospective (JPHC) study, 43,117 males and 50,193 females with no history of cancer or CVD finished the food frequency questionnaire (FFQ) and were included in the study. Intake of dairy products was assessed using the FFQ and adjusted for total energy by using the residual method. We used multivariate Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for mortality risk in males and females. Results 14,211 deaths in males and 9547 deaths in females from all causes were identified during an average follow-up of 19.3 years. For males, total dairy consumption was nonlinearly and significantly associated with lower risk of mortality from all causes [the third quartile, HR = 0.87 (0.83, 0.91), the fourth quartile, HR = 0.89 (0.85, 0.94), P for nonlinearity P for nonlinearity Conclusion For Japanese people, consumption of dairy products was associated with a decreased risk of mortality from all-cause and cardiovascular diseases among males.

The objective of this study was to identify the prevalence of family history of cancer using cohorts participating in the Japanese National Center Cohort Collaborative for Advancing Population Health (NC-CCAPH). We pooled data from seven eligible cohorts of the Collaborative with available data on family history of cancer. Prevalence of family history of cancer and corresponding 95% confidence intervals are presented for all cancers and selected site-specific cancers for the total population and stratified by sex, age, and birth cohort. Prevalence of family history of cancer increased with age ranging from 10.51% in the 15 to 39 year age category to 47.11% in 70-year-olds. Overall prevalence increased in birth cohorts from ≤ 1929 until 1960 and decreased for the next two decades. Gastric cancer (11.97%) was the most common site recorded for family members, followed by colorectal and lung (5.75%), prostate (4.37%), breast (3.43%) and liver (3.05%) cancer. Women consistently had a higher prevalence of family history of cancer (34.32%) versus men (28.75%). Almost one in three participants had a family history of cancer in this Japanese consortium study highlighting the importance of early and targeted cancer screening services.

The association between vitamin D and total and colorectal cancer risk was inconsistent in observational studies. We conducted Mendelian randomization approach in which the effect of confounding might be reduced. 110 single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D concentrations were systematically selected according to the “GWAS Catalog” from all ethnic populations. For the SNP-vitamin D concentration association, 3978 individuals from two Japanese cohorts were included. Regarding SNP-total and colorectal cancer association, 4543 cancer cases and 14,224 controls and 7936 colorectal cancer cases and 38,042 controls, respectively were included from the Japanese Consortium of Genetic Epidemiology and other studies in Japan. There was no significant association between the genetically predicted plasma 25-hydroxyvitamin D concentration and total or colorectal cancer in any of the MR analyses. Odds ratios per doubling in vitamin D concentration were 0.83 (95% confidence interval [CI] 0.63–1.09) for total cancer and 1.00 (95% CI 0.80–1.24) for colorectal cancer in inverse variance weighted method, 0.83 (95% CI 0.57–1.19) for total cancer and 1.01 (95% CI 0.75–1.37) for colorectal cancer in MR-Egger method. Consistent with previous MR analyses among European ancestries, there was no significant association identified between 25-hydroxyvitamin D levels and total or colorectal cancer among Asians.

The number of long-term survivors after a cancer diagnosis is increasing. Few investigations have compared survivors’ diets to their original pre-diagnosis dietary pattern or with the patterns of cancer-free controls. We examined the dietary changes in survivors for five years (i.e. before to after diagnosis) in cancer survivors, comparing them with cancer-free controls in a prospective cohort study in Japan. Using 1995–1998 for the baseline and 2000–2003 for the follow-up survey, a validated food frequency questionnaire was administered to 33,643 men and 39,549 women aged 45–74 years. During the follow-up period, 886 men and 646 women had developed cancer. Participants that had not been diagnosed with cancer served as controls. There was a greater decrease in the calorie intake (median change: − 168 kcal/d [Interquartile range: − 640, 278]) in male cancer survivors compared to controls (− 33 kcal/d [− 453, 380], P

PURPOSE: Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project. METHODS: Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI). RESULTS: Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25-2.03), always using table salt (aOR 1.33, 95% CI 1.16-1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01-1.51) vs. the lowest tertile. No significant association was observed for the highest vs. the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82-1.43). The results obtained were consistent across anatomic sites, strata of Helicobacter pylori infection, and sociodemographic, lifestyle and study characteristics. CONCLUSION: Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake.

Background Falls are important causes of injury and mortality in older people, and associated medical costs can be enormous. Physical activity (PA) is a potential preventive factor for falls. However, few studies have examined the effect of different types of PA on fall prevention. This study aimed to evaluate the association between PA levels and the incidence of recurrent falls by type of PA in middle-aged and older people. Methods This cohort study targeted 7,561 community-dwelling individuals aged 40–74 years who did not experience recurrent falls in the year before baseline. Information on PA levels, demographics, body size, lifestyle, and fall/disease history was obtained using a self-administered questionnaire in the baseline survey. Levels of total PA, leisure-time PA, and non-leisure-time PA (occupation, commuting, and housework) were estimated using metabolic equivalent (MET) scores (MET-h/day; hours spent on a given activity per day multiplied by its MET intensity). PA levels were categorized into four groups. Falls were recorded as none, once, or twice or more (recurrent falls). The outcome of the study was the incidence of recurrent falls in the past year before a survey conducted 5 years after the baseline survey. Logistic regression analyses were performed to calculate odds ratios for recurrent falls. Results Higher total PA and non-leisure-time PA levels were associated with a higher risk of recurrent falls (P for trend = 0.0002 and 0.0001, respectively), with the highest total PA and non-leisure-time PA groups having a significantly higher adjusted OR (1.96 [95%CI:1.33–2.88] and 2.15 [95%CI:1.48–3.14], respectively) relative to the lowest group (reference). As for leisure-time PA, the medium group had a significantly lower adjusted OR (0.70 [95%CI:0.49–0.99]) relative to the reference group. By sex, the adjusted OR in the medium leisure-time PA group was significantly lower relative to the reference group in women (0.50 [95%CI: 0.29–0.85]) but not in men. Conclusions Medium level leisure-time PA reduces the risk of recurrent falls in middle-aged and older people, whereas higher level non-leisure-time PA is associated with a higher risk of recurrent falls.

Long-term associations of dietary glycemic index (GI) and glycemic load (GL) with mortality outcomes remain unclear. The present analysis included 72,783 participants of the Japan Public Health Center-based Prospective Study. Participants who responded to the 5-year follow-up questionnaire in 1995–1999 were followed-up until December 2015. We estimated the risk of total and cause-specific mortality associated with GI and GL using Cox proportional hazards regression models. During 1,244,553 person years of follow-up, 7535 men and 4913 women died. GI was positively associated with all-cause mortality. As compared with the lowest quartile, the multivariable HR for those who had the highest quartile of GI was 1.14 (95% CI 1.08–1.20). The HRs for death comparing the highest with the lowest quartile were 1.28 (95% CI 1.14–1.42) for circulatory system diseases, 1.33 (95% CI 1.14–1.55) for heart disease, 1.32 (95% CI 1.11–1.57) for cerebrovascular disease, and 1.45 (95% CI 1.18–1.78) for respiratory diseases. GI was not associated with mortality risks of cancer and digestive diseases. GL showed a null association with all-cause mortality (highest vs lowest quartile; HR 1.04; 95% CI 0.96–1.12). However, among those who had the highest quartile of GL, the HRs for death from circulatory system diseases was 1.24 (95% CI 1.05–1.46), cerebrovascular disease was 1.34 (95% CI 1.03–1.74), and respiratory diseases was 1.35 (95% CI 1.00–1.82), as compared with the lowest quartile. In this large prospective cohort study, dietary GI and GL were associated with mortality risks.

To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. We detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improve the clinical characterization of CAD genetics and suggest the utility of trans-ancestry meta-analysis for PRS derivation in non-European populations.

Background Many epidemiological studies have reported the association between exposure to particulate matter and mortality, but long-term prospective studies from Asian populations are sparse. Furthermore, associations at low levels of air pollution are not well clarified. Here, we evaluated associations between long-term exposure to particulate matter 3 (PM2.5) and mortality in a Japanese cohort with a relatively low exposure level. Methods The Japan Public Health Center-based Prospective Study (JPHC Study) is a prospective cohort study of men and women aged 40-69 years in 1990 who were followed up through 2013 for mortality. In this cohort of 87,385 subjects who did not move residence during follow-up, average PM2.5 levels from 1998 to 2013 by linkage with 1-km2 grids of PM2.5 concentration were assigned to the residential addresses of all participants. To avoid exposure misclassification, we additionally evaluated the association between 5-year (1998-2002) cumulative exposure level and mortality during the follow-up period from 2003 to 2013 in 79,078 subjects. Cox proportional hazards models were used to calculate the association of long-term exposure to PM2.5 on mortality, with adjustment for several individual confounding factors. Results Average PM2.5 was 11.6 µg/m3. Average PM2.5 exposure was not associated with all-cause mortality or cancer and respiratory disease mortality. However, average PM2.5 was positively associated with mortality from cardiovascular disease (hazard ratio (HR) of 1.23 (95%CI=1.08-1.40) per 1-µg/m3 increase; in particular, HR in mortality from cerebrovascular disease was 1.34 (95%CI=1.11-1.61) per 1-µg/m3 increase. Additionally, these results using cumulative 5-year PM2.5 data were similar to those using average PM2.5 over 15 years. Conclusions We found evidence for a positive association between PM2.5 exposure and mortality from cardiovascular disease in a Japanese population, even in an area with relatively low-level air pollution.

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. 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. 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. Intake of fermented soy products such as natto was inversely associated with the risk of CVD in women.

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.

The overwhelming majority of participants in current genetic studies are of European ancestry. To elucidate disease biology in the East Asian population, we conducted a genome-wide association study (GWAS) with 212,453 Japanese individuals across 42 diseases. We detected 320 independent signals in 276 loci for 27 diseases, with 25 novel loci (P < 9.58 × 10-9). East Asian-specific missense variants were identified as candidate causal variants for three novel loci, and we successfully replicated two of them by analyzing independent Japanese cohorts; p.R220W of ATG16L2 (associated with coronary artery disease) and p.V326A of POT1 (associated with lung cancer). We further investigated enrichment of heritability within 2,868 annotations of genome-wide transcription factor occupancy, and identified 378 significant enrichments across nine diseases (false discovery rate < 0.05) (for example, NKX3-1 for prostate cancer). This large-scale GWAS in a Japanese population provides insights into the etiology of complex diseases and highlights the importance of performing GWAS in non-European populations.

Fruits and vegetables may induce greater satiety, reduce hunger, decrease energy intake, and modulate energy metabolism, thereby playing a role in weight loss. To determine the associations between changes in fruit and vegetable consumption and weight change over a 5-year interval in Japanese adults. This cohort study included 54,015 subjects (54.6% female, mean age 56.5 years) of the Japan Public Health Center-based Prospective Cohort Study who had no known history of major chronic diseases at baseline. Data on fruit and vegetable consumption were collected using a validated food frequency questionnaire. Body weight was self-reported. We used multivariable linear mixed-effects regression models to examine the associations between changes in fruit and vegetable consumption and change in body weight. On average, body weight decreased by 25 g [95% confidence interval (CI), 3, 47] for every 100 g/d increase in total vegetable consumption. Change in fruit consumption was nonlinearly associated with weight change. Fruit consumption was directly associated with weight change among subjects who increased consumption (70 g; 95% CI, 39, 101) but was not associated with weight change among subjects who reduced or did not change fruit consumption. These associations did not vary by sex, age, and body mass index (BMI) at baseline. The association with vegetables was restricted to yellow/red vegetables (− 74 g; 95% CI, − 129, − 18) and allium vegetables (− 129 g; 95% CI, − 231, − 28). Lower-fiber vegetables were inversely associated with weight change, whereas lower-fiber fruits or higher-energy fruits were directly associated with weight change beyond 0 g/d change in consumption. Change in vegetable consumption was inversely associated with weight change while fruit consumption was positively associated with weight change among subjects who increased consumption. The influence of fruits and vegetables on weight change may depend on the characteristics of the fruits and vegetables.

Background Income inequality has dramatically increased worldwide, and there is a need to re-evaluate the association between socio-economic status (SES) and depression. Relative contributions of household income and education to depression, as well as their interactions, have not been fully evaluated. This study aimed to examine the association between SES and depressive symptoms in Japanese adults, focusing on interactions between education and household income levels. Methods This cross-sectional study used data from baseline surveys of two cohort studies. Participants were 38,499 community-dwelling people aged 40–74 years who participated in baseline surveys of the Murakami cohort study (2011–2012) and Uonuma cohort study (2012–2015) conducted in Niigata Prefecture, Japan. Information regarding marital status, education level, household income, occupation, activities of daily living (ADL), and history of cancer, myocardial infarction, stroke, and diabetes was obtained using a self-administered questionnaire. Depressive symptoms were examined using the Center for Epidemiologic Studies Depression Scale (CES-D). Logistic regression analysis was used to obtain odds ratios (ORs). Covariates included age, sex, marital status, education, household income, occupation, ADL, and disease history. Results Individuals with higher education levels had lower ORs (adjusted P for trend = 0.0007) for depressive symptoms, independently of household income level. The OR of the university-or-higher group was significantly lower than that of the junior high school group (adjusted OR = 0.79). Individuals with lower household income levels had higher ORs (adjusted P for trend Conclusions Both education and household income levels are independently associated with the prevalence of depressive symptoms, with household income levels showing a more robust association with depressive symptoms than education levels. This suggests that a high household income level may offset the risk of depressive symptoms from having a low education level.

Heterocyclic aromatic amines (HAAs), which are formed from the reaction of creatine or creatinine, amino acids, and sugars in meat and fish cooked at high temperatures, have been shown to be mutagenic in bacterial assays and carcinogenic in animal models. Following advances in the dietary assessment of HAA intake in epidemiological studies - including development of a validated meat-cooking module and a specialized food composition database - a number of epidemiological studies have specifically examined the association of HAA intake and cancer risk, most of which were conducted in Western countries. Given that dietary habits and cooking methods differ across countries, however, epidemiological investigation of dietary HAA intake requires a population-specific assessment method. Here, we developed a practical method for assessing dietary HAA intake among Japanese using a food frequency questionnaire (FFQ) and evaluated its validity for use in epidemiological studies by comparison with 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) levels in human hair. The Japan Public Health Center-based Prospective Study reported that daily intake of HAAs among Japanese was relatively low, and that more than 50% of total intake in mainland Japan was derived from fish. Only four case-control studies in Japan have been reported so far, for colorectal, stomach and prostate cancer, and colorectal adenoma. A statistically significant positive association was found between 2-amino-3,4-dimethylimidazo [4,5-f] quinoline (MeIQ) and the risk of colorectal adenoma and between individual and total HAAs and the risk of prostate cancer. In contrast, no association was observed for colorectal or stomach cancer, or for colorectal adenoma among men. We also found that the limited and inconsistent findings among epidemiological studies are due to the difficulty in assessing exposure levels of HAAs. In addition to further evidence from prospective cohort studies in Japanese based on dietary HAA intake estimated by FFQs, studies using other methods to assess HAA exposure, such as biomarkers, are highly anticipated.

Eating a variety of foods has been recommended in the dietary guidelines of many developed nations, as well as global dietary guidelines. We investigated the potential effect of dietary diversity on the risk of total mortality and major causes of mortality in a large-scale cohort study involving the Japanese population. From 1995 to 2012, 79,904 participants (37,240 men and 42,664 women) aged 45 to 74 years, without histories of ischemic heart disease, stroke, or cancer were followed-up for a median of 14.9 years. We used 133 food and beverage items listed on a 5-year follow-up food frequency questionnaire, and the daily frequency of consumption for each item (excluding five alcoholic beverages) was counted. Multivariable-adjusted Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to compare the highest and lowest quintiles. An inverse association was identified between total dietary diversity and mortality rates in women (highest quintile HR: 0.81; 95% CI: 0.71, 0.92; p for trend = 0.002) but the same trend was not observed in men (highest quintile HR: 0.96; 95% CI: 0.87, 1.10; p for trend = 0.266). In addition, fruit diversity was associated with lower mortality rates in men (highest quintile HR: 0.87; 95% CI: 0.79, 0.95; p for trend = 0.006), whereas soy diversity was associated with lower mortality rates in women (highest quintile HR: 0.89; 95% CI: 0.79, 1.00; p for trend = 0.004). With regard to men, meat and fish diversity were associated with higher mortality rates (highest quintiles of meat and fish diversity HR: 1.15 [95% CI: 1.06, 1.25] and 1.12 [95% CI: 1.02, 1.22], respectively). These findings indicate that consuming a greater diversity of total foods and increasing the diversity of fruit and soy consumed have considerable public health implications.

Little is known about the risk of cerebrovascular disease in cancer survivors. We aimed to assess the association between incident cancer and the subsequent risk of stroke using a large-scale, population-based prospective study. 74,530 Japanese aged between 40 and 69 years at baseline study were matched by the status of cancer diagnosis during follow-up using propensity score nearest-neighbor matching with allowance for replacement. A total of 2242 strokes were reported during 557,885 person-years of follow-up. Associations between incident cancer and the subsequent risk of all strokes, cerebral infarction, and intracerebral hemorrhage were assessed using a Cox proportional hazards model stratified on the propensity score-matched pairs. No significant association was observed between the status of cancer diagnosis of all types, gastric, colorectal and lung cancer, and subsequent occurrence of all strokes, cerebral infarction, and intracerebral hemorrhage. However, analysis by discrete time periods suggested an elevated risk in cancer patients for one to three months after a cancer diagnosis in all stroke (HR, 2.24; 95% CI, 1.06, 4.74) and cerebral infarction (HR, 2.62; 95% CI, 1.05, 6.53). This prospective cohort study found no association between the status of cancer diagnosis and the subsequent occurrence of all strokes and its subtypes during the entire follow-up period but suggested an increase in stroke risk during the active phase of malignancy.

Physical activity is associated with subjective well-being. In rural communities, however, physical activity may be affected by environmental factors (e.g., nature and socioecological factors). We examined the association of two physical activities in rural life (farming activity and snow removal) with subjective well-being in terms of happiness and ikigai (a Japanese word meaning purpose in life). In this cross-sectional study, we analysed data collected from community-dwelling adults aged ≥ 40 years in the 2012–2014 survey of the Uonuma cohort study, Niigata, Japan. Happiness (n = 31,848) and ikigai (n = 31,785) were evaluated with respect to farming activity from May through November and snow removal from December through April by using an ordinal logistic regression model with adjustments for potential confounders. The analyses were conducted in 2019. Among the participants who reported some farming or snow-removal time, median farming and snow-removal time (minutes per day) was 90.0 and 64.3 for men and 85.7 and 51.4 for women, respectively. Ordinal logistic regression analysis showed that longer time farming was associated with greater happiness and ikigai in men (adjusted odds ratio for first vs. fourth quartile: happiness = 1.17, 95% confidence interval [CI] = 1.01, 1.35; ikigai = 1.29, 95% CI = 1.10, 1.50), and also in women (adjusted odds ratio for first vs. fourth quartile: happiness = 1.17, 95% CI = 1.001, 1.36; ikigai = 1.42, 95% CI = 1.20, 1.67). More snow-removal time was inversely associated with happiness and with ikigai in women only (adjusted odds ratio for first vs. fourth quartile: happiness = 0.75, 95% CI = 0.67, 0.85; ikigai = 0.78, 95% CI = 0.69, 0.88). Our findings showed that physical activity in rural life was associated with happiness and with ikigai, and gender differences were observed in their associations with more snow-removal time. These results may be useful in helping to identify people in rural communities who are vulnerable in terms of psychological well-being.

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.

Genome-wide association studies (GWAS) have successfully identified about 70 genomic loci associated with breast cancer. Owing to the complexity of linkage disequilibrium and environmental exposures in different populations, it is essential to perform regional GWAS for better risk prediction. This study aimed to investigate the genetic architecture and to assess common genetic risk model of breast cancer with 6,669 breast cancer patients and 21,930 female controls in the Japanese population. This GWAS identified 11 genomic loci that surpass genome-wide significance threshold of P −8 with nine previously reported loci and two novel loci that include rs9862599 on 3q13.11 (ALCAM) and rs75286142 on 21q22.12 (CLIC6-RUNX1). Validation study was carried out with 981 breast cancer cases and 1,394 controls from the Aichi Cancer Center. Pathway analyses of GWAS signals identified association of dopamine receptor medicated signaling and protein amino acid deacetylation with breast cancer. Weighted genetic risk score showed that individuals who were categorized in the highest risk group are approximately 3.7 times more likely to develop breast cancer compared to individuals in the lowest risk group. This well-powered GWAS is a representative study to identify SNPs that are associated with breast cancer in the Japanese population.

Epidemiological studies have suggested a protective effect of dietary fiber intake on breast cancer risk while the results have been inconsistent. Our study aimed to investigate the association between dietary fiber intake and breast cancer risk and to explore whether this association is modified by reproductive factors and hormone receptor status of the tumor. A total of 44,444 women aged 45 to 74 years from the Japan Public Health Center-based Prospective Study were included in analyses. Dietary intake assessment was performed using a validated 138-item food frequency questionnaire (FFQ). Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer incidence were calculated by multivariate Cox proportional hazards regression models. During 624,423 person-years of follow-up period, 681 breast cancer cases were identified. After adjusting for major confounders for breast cancer risk, inverse trends were observed but statistically non-significant. Extremely high intake of fiber was associated with decreased risk of breast cancer but this should be interpreted with caution due to limited statistical power. In stratified analyses by menopausal and hormone receptor status, null associations were observed except for ER-PR- status. Our findings suggest that extreme high fiber intake may be associated with decreased risk of breast cancer but the level of dietary fiber intake among Japanese population might not be sufficient to examine the association between dietary fiber intake and breast cancer risk.

Aims/hypothesis: The aims of the study were to evaluate the association between type 2 diabetes and the risk of death from any cancer and specific cancers in East and South Asians. Methods: Pooled analyses were conducted of 19 prospective population-based cohorts included in the Asia Cohort Consortium, comprising data from 658,611 East Asians and 112,686 South Asians. HRs were used to compare individuals with diabetes at baseline with those without diabetes for the risk of death from any cancer and from site-specific cancers, including cancers of the oesophagus, stomach, colorectum, colon, rectum, liver, bile duct, pancreas, lung, breast, endometrium, cervix, ovary, prostate, bladder, kidney and thyroid, as well as lymphoma and leukaemia. Results: During a mean follow-up of 12.7 years, 37,343 cancer deaths (36,667 in East Asians and 676 in South Asians) were identified. Baseline diabetes status was statistically significantly associated with an increased risk of death from any cancer (HR 1.26; 95% CI 1.21, 1.31). Significant positive associations with diabetes were observed for cancers of the colorectum (HR 1.41; 95% CI 1.26, 1.57), liver (HR 2.05; 95% CI 1.77, 2.38), bile duct (HR 1.41; 95% CI 1.04, 1.92), gallbladder (HR 1.33; 95% CI 1.10, 1.61), pancreas (HR 1.53; 95% CI 1.32, 1.77), breast (HR 1.72; 95% CI 1.34, 2.19), endometrium (HR 2.73; 95% CI 1.53, 4.85), ovary (HR 1.60; 95% CI 1.06, 2.42), prostate (HR 1.41; 95% CI 1.09, 1.82), kidney (HR 1.84; 95% CI 1.28, 2.64) and thyroid (HR 1.99; 95% CI 1.03, 3.86), as well as lymphoma (HR 1.39; 95% CI 1.04, 1.86). Diabetes was not statistically significantly associated with the risk of death from leukaemia and cancers of the bladder, cervix, oesophagus, stomach and lung. Conclusions/interpretation: Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality. © 2017, Springer-Verlag Berlin Heidelberg.

Although vitamin D has been experimentally reported to inhibit tumorigenesis, cell growth and prostate cancer invasion, epidemiologic data regarding prostate cancer risk are inconsistent, and some studies have suggested positive but nonsignificant associations. Further, the impact of vitamin D on prostate cancer between Western and Japanese populations may differ due to different plasma vitamin D levels.We performed a nested case-control study within the Japan Public Health Center-based Prospective (JPHC) Study in 14,203 men (40-69 years) who answered a self-administered questionnaire at baseline (1990-1994) and gave blood samples, and were followed until 2005. We identified 201 prostate cancers which are newly diagnosed during follow-up (mean 12.8 years). We selected two matched controls for each case from the cohort. We used a conditional logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer with respect to levels of 25-hydroxy vitamin D (25(OH)D) in plasma.We did not observe statistically significant association between 25(OH)D level and total prostate cancer (multivariate OR=1.13 (95%CI=0.66-1.94, P25(OH)D level showed no association with overall prostate cancer among Japanese men in this large cohort.

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; PSKAT-O, 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 Acid-base imbalance might promote the progression of chronic kidney disease (CKD), but whether nutrient-derived dietary acid load increases the risk of albuminuria or even high normoalbuminuria is unclear. Methods A Japanese cohort comprising 3250 men and 3434 women aged 40–97 years with urine albumin-to-creatinine ratio (ACR)

Helicobacter pylori (H. pylori), an established risk factor for gastric cancer, is suggested to also play a role in the development of pancreatic cancer; however, the association remains inconclusive. We examined this association among Japanese men and women. H. pylori and atrophic gastritis (AG) status were determined serologically, using blood sample collected during health checkups. A total of 20,116 subjects enrolled in the Japan Public Health Center-based Prospective Study Cohort II with available data on H. pylori seropositivity (anti-H. pylori) and AG were followed until the end of 2010. Cox proportional hazards models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI), using the information from the baseline survey. During 320,470 person-years of follow-up, 119 cases of pancreatic cancer were identified. No statically significant increase or decrease in pancreatic cancer risk was observed for H. pylori and AG status, independently or in combination. In a multivariable-adjusted model, we observed a non-significant decrease in the risk among those who had AG but were anti-H. pylori seronegative (HR 0.57, 95% CI 0.31–1.03). In a stratified analysis, we observed a statistically significant increased risk of pancreatic cancer for AG+ (HR 3.64, 95% CI 1.37–9.66), and AG+/anti-H. pylori− or AG+/anti-H. pylori+ (HR 5.21, 95% CI 1.14–23.87) among current smokers. Non-smokers in all categories of AG and anti-H. pylori showed a non-statistical decrease in the risk. There was no statistically significant interaction between H. pylori infection, AG status, and smoking status. Our findings suggest H. pylori seropositivity and AG, individually or in combination, are not associated with the risk of pancreatic cancer in a general Japanese population. Among current smokers, pancreatic cancer risk increased with AG, regardless of H. pylori infection status.

The aim of this study was for the first time to assess the association between glycemic index (GI), glycemic load (GL), and colorectal cancer using a prospective Japanese population-based cohort. In our study participants aged 40–69 at baseline of the Japan Public Health Center-based prospective Study (JPHC Study) in 10 prefectural public health centers (PHC) were included. Subjects responding to the five-year follow-up survey (1995–1999) without previous history of cancer and missing data were included in the current analysis n = 73,501 (men n = 34,560 and women n = 38,941). We reported results as hazard ratios (HR) and 95 % confidence intervals (CI) by Cox proportional hazards modeling. The average follow-up time was 12.5 years (919,276 person-years). A total of 1,468 colorectal cancer cases were detected. Overall, no significant results were observed; however, GL was inversely nonsignificantly associated with colon cancer in men HR = 0.74 (95 % CI 0.51–1.09) and rectal cancer in women 0.52 (95 % CI 0.24–1.14). The GL tended to be inversely associated with proximal colon cancer among men 0.62 (95 % CI 0.36–1.08), while a positive association with the GI was observed among women 1.37 (95 % CI 0.88–2.14). Sensitivity analyses excluding the first three years of observation showed similar results. Results stratified by diabetes status, BMI, smoking and red meat were nonsignificant. In conclusion, the prospective JPHC Study suggests that the GI and GL do not have a substantial impact on the risk of colorectal cancer in Japanese adults.

Previous studies have consistently reported an association between circulating levels of branched-chain amino acids (BCAAs) or adipokines and insulin resistance; however, the association between BCAA and adipokine levels remains to be clarified. In this cross-sectional study involving 678 participants (435 men) without diabetes, plasma BCAA (valine, leucine, and isoleucine), adipokine (total and high molecular weight [HMW] adiponectin, leptin, and tumor necrosis factor-α [TNF-α]) concentrations, and an updated homeostasis model assessment of insulin resistance (HOMA2-IR) were measured. The association between the concentrations of total BCAAs and adipokines was adjusted for confounding factors, including body mass index. For the lowest and highest BCAA quartiles, the adjusted geometric mean levels of HMW adiponectin were, respectively, 1.51 and 0.91 μg/mL, in men (P for trend

Evidence regarding stress as a risk factor for cancer onset is inconsistent. In this study, based on the Japan Public Health Center-based Prospective Study, we enrolled 101,708 participants aged 40–69 years from 1990–1994. The self-reported perceived stress level was collected at baseline and updated through 5-year follow-up. The association between perceived stress and cancer risk was measured by Cox proportional hazards regression model, adjusted for all known confounders. During follow-up (mean = 17.8 years), we identified 17,161 cancer cases. We found no association between baseline perceived stress level and cancer incidence. However, by taking account of the dynamic changes in perceived stress, time-varying analyses revealed a slightly (4–6%) increased overall cancer risk for subjects under elevated perceived stress levels compared to the ‘low stress level’ group. Analyses concerning long-term perceived stress level showed that individuals with constantly high perceived stress level had an 11% (95% confidence interval 1–22%) excess risk for cancer compared to subjects with persistently low stress levels. This association was confined to men (20% excess risk), and was particularly strong among smokers, alcohol drinkers, obese subjects, and subjects without family history of cancer. Therefore, we concluded high perceived stress level might contribute to excess overall cancer incidence among men.

In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified three novel genetic loci associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene, P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene, P = 1.67 × 10−9), and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene, P = 4.25 × 10−8). These associations were replicated in European-ancestry populations including 16,003 cases and 41,335 controls (P = 0.030, 0.004, and 0.010, respectively). Data from the ENCODE project suggest that variants rs4951011 and rs10474352 may be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.

Clarification of the putative etiologic role of heterocyclic aromatic amines (HAAs) in the development of cancer requires a validated assessment tool for dietary HAAs. This study primarily aimed to evaluate the validity of a food frequency questionnaire (FFQ) in estimating HAA intake, using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) level in human hair as the reference method.We first updated analytical methods of PhIP using liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS/MS) and measured 44 fur samples from nine rats from a feeding study as part-verification of the quantitative performance of LC-ESI/MS/MS. We next measured PhIP level in human hair samples from a validation study of the FFQ (n = 65). HAA intake from the FFQ was estimated using information on intake from six fish items and seven meat items and data on HAA content in each food item. Correlation coefficients between PhIP level in human hair and HAA intake from the FFQ were calculated.The animal feeding study of PhIP found a significant dose-response relationship between dosage and PhIP in rat fur. Mean level was 53.8 pg/g hair among subjects with values over the limit of detection (LOD) (n = 57). We found significant positive correlation coefficients between PhIP in human hair and HAA intake from the FFQ, with Spearman rank correlation coefficients of 0.35 for all subjects, 0.21 for subjects with over LOD values, and 0.34 for subjects with over limit of quantification.Findings from the validation study suggest that the FFQ is reasonably valid for the assessment of HAA intake.

Background: Global hypomethylation has been suggested to cause genomic instability and lead to an increased risk of cancer. We examined the association between the global methylation level of peripheral blood leukocyte DNA and breast cancer among Japanese women. Methods: We conducted a hospital-based case–control study of 384 patients aged 20–74 years with newly diagnosed, histologically confirmed invasive breast cancer, and 384 matched controls from medical checkup examinees in Nagano, Japan. Global methylation levels in leukocyte DNA were measured by LUminometric Methylation Assay. Odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between global hypomethylation and breast cancer were estimated using a logistic regression model. Results: Compared with women in the highest tertile of global methylation level, ORs for the second and lowest tertiles were 1.87 (95% CI=1.20–2.91) and 2.86 (95% CI=1.85–4.44), respectively. Global methylation levels were significantly lower in cases than controls, regardless of the hormone receptor status of the cancer (all P values for trend

Epidemiological evidence for the impact of fruit and vegetable intake on breast cancer risk among the Japanese populations is scarce.The purpose of this study was to evaluate the association between fruit and vegetable intake and breast cancer risk among 47,289 Japanese women.The study was conducted under a population-based prospective cohort design. Dietary assessment was performed using a validated food frequency questionnaire. A Cox proportional hazards regression model was used to calculate relative risks (RRs) and their corresponding 95 % confidence intervals (CIs).During an average of 10.2 years of follow-up, 452 cases of breast cancer were newly diagnosed. No association with breast cancer risk was seen for intake of total fruits and vegetables, cruciferous vegetables, green-leaf vegetables, yellow vegetables, or tomato products in overall or postmenopausal women. Cruciferous vegetable intake was associated with a statistically significant decrease in risk of premenopausal breast cancer [multivariable-RRQ4 vs. Q1 = 0.64 (95 % CI = 0.38-1.10; p trend = .046)] and showed a marginally inverse association with ER+ PR+ tumors [RRper 100 g increment = 0.64 (95 % CI = 0.41-1.00)]. In contrast, positive associations were seen between intake of total fruits and citrus fruits and breast cancer risk in overall and premenopausal women. However, these associations for fruit were all attenuated with additional adjustment for vitamin C intake.Our results suggest an overall null association between total fruit and vegetable intake and breast cancer risk. Intake of cruciferous vegetable showed a statistically significant association with a decreased risk of breast cancer among premenopausal women.

In recent years, diabetes has been shown to be associated with cancer risk, and this has led to a joint committee being formed, enlisting experts from the Japan Diabetes Society (JDS) and the Japanese Cancer Association (JCA) to address this issue. Epidemiological data in Japan provides evidence to demonstrate that diabetes is associated with increased risk for cancers, especially colorectal, liver, and pancreatic cancers. The mechanisms through which diabetes is assumed to promote oncogenesis include insulin resistance and associated hyperinsulinemia, hyperglycemia and inflammation. Common risk factors for type 2 diabetes and cancer include aging, male sex, obesity, physical inactivity, inappropriate diet (excessive red/processed meat intake, inadequate vegetable/fruit/dietary fiber intake), excessive alcohol drinking, and smoking. Given that inappropriate diet/exercise, smoking and excessive alcohol drinking are common risk factors for diabetes and cancer, diet/exercise therapy, smoking cessation and alcohol moderation may be associated with decreased risk for cancer in diabetic patients. There is as yet limited evidence as to whether any particular anti-diabetic agents may influence cancer risk.

Purpose Arsenic is a known human carcinogen and has been linked to adverse health outcomes, including cancer. However, the effects of arsenic exposure from food on health are still unknown. We researched to examine the association between arsenic exposure from food and incidence of cancer in a Japanese population. Methods We conducted a population-based prospective study in 90,378 Japanese men and women aged 45–74 years. Participants responded to a validated questionnaire that included 138 food items. We estimated dietary arsenic intake from 12 food groups (75 items) based on the questionnaire data. During 11 years of follow-up, 7,002 cancer cases were identified. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for cancer were calculated by Cox proportional hazards modeling. Results Total arsenic and inorganic arsenic showed no association with the risk of total cancer in both men and women. Total arsenic and inorganic arsenic intake tended to be associated with an increased risk of lung cancer in men. In particular, these positive associations were strengthened in currently smoking men, with HRs (95 % CI) in the highest categories of arsenic and inorganic arsenic intake compared with the lowest of 1.29 (95 % CI = 1.03–1.61) and 1.36 (95 % CI = 1.09–1.70), respectively. We also detected an interaction between arsenic and inorganic arsenic intake and smoking status in men (pinteraction

Corrigendum: Genome-wide association study of colorectal cancer identifies six new susceptibility loci

Accumulating evidence has implicated insulin and the insulin-like growth factor (IGF) axis in colorectal carcinogenesis. Of interest, adiposity is likely to impose a greater risk on men than on women, which indicates that the association of insulin and the IGF axis with colorectal neoplasia may differ by gender. However, epidemiological evidence for this possible gender difference is limited to date.We measured plasma concentrations of C-peptide, IGF-I and IGF-binding proteins (IGFBPs) 1 and 3 in 1520 healthy volunteer examinees who underwent total colonoscopy between February 2004 and February 2005, and cross-sectionally investigated the association of these biomarkers with colorectal adenoma by gender. An unconditional logistic regression model was used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for colorectal adenoma after adjustment for potential confounders.We observed a positive association of C-peptide and IGF-I (P (trend)0.001 and 0.02, respectively) and an inverse association of IGFBP-1 (P (trend)=0.002) with colorectal adenoma in men. Adjusted ORs of colorectal adenoma for the highest compared with the lowest quartile were also statistically significant for C-peptide (OR: 2.62, 95% CI: 1.71-4.01), IGF-I (OR: 1.63, 95% CI: 1.08-2.46) and IGFBP-1 (OR: 0.49, 95% CI: 0.32-0.75). In contrast, no measurable association was seen in women. Corresponding ORs for C-peptide, IGF-I and IGFBP-1 were 0.98 (95% CI: 0.56-1.71), 0.79 (95% CI: 0.44-1.43) and 1.05 (95% CI: 0.60-1.86), respectively. The gender difference was statistically significant for C-peptide (P (interaction)=0.03) and marginally significant for IGF-I and IGFBP-1 (P (interaction)=0.14 and 0.12, respectively).Our observations suggest that insulin and the IGF axis act differently by gender in colorectal carcinogenesis, at least in its early stage. The findings of this study further our understanding of the complexities of the gender difference in the association between adiposity and colorectal neoplasia.

The anticarcinogenic potential of green tea and coffee might be expected to reduce the risk of thyroid cancer, but epidemiological evidence is sparse. We examined green tea and coffee consumption in association with thyroid cancer risk in a general Japanese population.We analyzed data from a prospective cohort of 100,507 persons (48,802 men; 51,705 women) aged 40-69. Green tea and coffee consumption were assessed via a self-administered questionnaire. During a mean 14.2-year follow-up, we documented 159 thyroid cancer cases (26 in men; 133 in women), and Cox regression were used to calculated hazard ratios (HRs).Green tea consumption was not found to be associated with thyroid cancer risk in general. However, when women were stratified by menopausal status, the multivariable HR for ≥ 5 cups/day versus1 cup/day was 1.66 (95% confidence interval (CI) = 0.85-3.23, trend p = 0.04) in premenopausal women, and was 0.47 (95% CI = 0.23-0.96, trend p = 0.06) in postmenopausal women. We found no association between coffee consumption and thyroid cancer risk in either sex.High green tea consumption may be positively associated with premenopausal thyroid cancer risk, but inversely associated with postmenopausal thyroid cancer risk.

Purpose We developed and evaluated a simple, robust and valid self-administered questionnaire for the estimation of physical activity (PA). Here, we examined the validity of this questionnaire in subjects with differing sex, ages, occupations and living circumstances.

Few studies have investigated the association between socioeconomic status and the survival of cancer patients in Japan.We examined whether occupation or educational level was associated with the survival of 725 gastric cancer patients who were diagnosed within an ongoing large population-based cohort study.After adjustment for age at diagnosis, and sex, we found that, compared with professionals or office workers, unemployed subjects (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.27-3.92) and manual laborers (HR, 1.68; 95% CI, 1.07-2.62) had an increased risk of gastric cancer death. After further adjustment for the clinical extent of disease, the increased risk disappeared. Educational level was not associated with the risk.These findings suggest that a disparity in survival by occupation exists among Japanese gastric cancer patients, largely due to a lower proportion of early disease among the unemployed and manual laborers.

Self-reporting provides useful information for assessing the risk factors of osteoporotic fractures in large cohort studies. However, to data, no studies in Japan have confirmed the accuracy of this approach in this context. The aim of the study reported here was to determine the positive predictive value (PPV) for the self-reporting of fractures. A total of 133 participants of the Oguni cohort in the Japan Public Health Center-based Prospective Study who reported a vertebral, upper limb, or hip fracture on the 15-year follow-up questionnaire survey were evaluated. The accuracy of fractures was confirmed by cross-referencing medical records. The average age of the participants was 72.4 (standard deviation 7.9) years. The PPV for vertebral fracture in the last 15 years was 17/20 (85.0%) for women and 2/9 (22.2%) for men, for a total of 19/29 (65.5%). PPVs for upper limb and hip fractures were as low as 30/68 (44.1%) and 12/22 (54.5%), respectively. Female self-reporting provided PPVs suitable for symptomatic vertebral fracture over 15 years and can be used as an outcome measure in large cohort studies in Japan.

Although many in vitro and animal studies have suggested a protective effect of green tea against breast cancer, findings from epidemiological studies have been inconsistent. No study has used prediagnostic biomarkers of tea polyphenols, which might play a protective role. A total of 24,226 women aged 40 to 69 years in the Japan Public Health Center-based Prospective Study who responded to the baseline questionnaire and provided blood in 1990-1995 were followed to December 2002. During a mean 10.6 years of follow-up, 144 newly diagnosed breast cancers were identified. Two matched controls for each case were selected from the cohort. Plasma levels of (-)-epigallocatechin (EGC), (-)-epicatechin (EC), (-)-epigallocatechin-3-gallate (EGCG), and (-)-epicatechin-3-gallate (ECG) were measured, and the odds ratio (OR) of breast cancer according to plasma level was estimated using a conditional logistic regression model. We found no statistically significant association between plasma tea polyphenol levels and breast cancer risk. Adjusted ORs for the highest versus lowest group were 0.90 (95% CI 0.42-1.96; P for trend = 0.98) for EGC, 0.95 (95% CI 0.43-2.08; P for trend = 0.86) for EC, 1.21 (95% CI 0.52-2.80; P for trend = 0.53) for EGCG, and 1.75 (95% CI 0.81-3.78; P for trend = 0.15) for ECG. Stratified analyses according to baseline menopausal status showed no remarkable difference between two strata. This nested case-control study found no overall association between plasma tea polyphenols and the risk of breast cancer in Japan.

This study investigated the association between glutathione S-transferases (GST) polymorphisms and immunoglobin G (IgG) titer levels in serum against Helicobacter pylori (H. pylori). Out of a total 300 healthy subjects seropositive for H. pylori, we analyzed the relationship between 15 single-nucleotide polymorphisms (SNPs), namely two in GST-mu2 (GST-M2), five in GST-mu3 (GST-M3), four in GST-pi1 (GST-P1) and four in GST-theta2 (GST-T2), and IgG antibody titer levels in serum against cytotoxin-associated gene A (CagA) and the surface antigen of H. pylori (Hp), as well as the levels of pepsinogen I (PGI). Titer levels were classified by tertile. The age-sex adjusted odds ratios (ORs) and 95% confidence intervals (CIs) in the middle and low titer groups were calculated using a polytomous logistic regression model, with the high titer group considered as control. Results for GST-M3 showed a significant association between SNPs, CagA and Hp titers. In addition, the AA genotype (high enzyme activity) from SNP rs7483 (Val224Ile) in GST-M3 showed a significantly low risk for being in the low titer group (OR: 0.48, 95% CI: 0.27-0.86 and OR: 0.46, 95% CI: 0.26-0.83 for CagA and Hp, respectively). Furthermore, the AA genotype from the rs7483 SNP showed significantly (P

We conducted a case–control study in a Japanese population to investigate the association between dietary isoflavone intake and the risk of colorectal adenoma. Participants who underwent magnifying colonoscopy with dye spreading as part of a cancer screening programme responded to a self-administered questionnaire, which included lifestyle information and intake of 145 food items, before the colonoscopy. A total of 721 case and 697 control subjects were enrolled. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. We found a significant inverse association between dietary isoflavone intake and the risk of colorectal adenoma in men and women combined. However, the inverse association was not linear; rather, all quartiles above the first showed a similar decrease in risk, with multivariable-adjusted ORs and 95% CIs compared with the lowest quartile of 0.77 (0.57–1.04), 0.76 (0.56–1.02) and 0.70 (0.51–0.96) in the second, third and highest quartiles, respectively (P for trend=0.03). Of interest, the observed association was more prominent in women than in men. The observed ceiling effect associated with higher isoflavone intake suggests that a lower intake of dietary isoflavone might be associated with an increased risk of colorectal adenoma in Japanese populations.