Association of dietary diversity with total mortality and major causes of mortality in the Japanese population: JPHC study.

BACKGROUND/OBJECTIVES: 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. SUBJECTS/METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Fish intake and risk of mortality due to aortic dissection and aneurysm: A pooled analysis of the Japan cohort consortium.

BACKGROUND & AIMS: Many studies have suggested that fish intake is associated with protection from risk of atherosclerotic diseases; however, this association with aortic diseases has not been elucidated worldwide. We hypothesized that fish intake is inversely associated with mortality from aortic diseases (aortic dissection and aneurysm). METHODS: The study was conducted as a pooled analysis of original data from a maximum of 8 cohort studies, comprising a total of 366,048 community-based men and women who had no history of cardiovascular disease or cancer. In each cohort, we used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality from aortic dissection, aneurysm and total aortic disease according to the frequency of fish intake and estimated summary HRs derived from each study. RESULTS: Nonlinear inverse associations were found between fish intake and total aortic disease. Compared with persons who ate fish 1-2 times/week, persons who seldom ate fish had higher mortality from total aortic disease (multivariable-adjusted pooled HR = 1.93; 95% CI, 1.13-3.31). Higher mortality was not seen in those who ate fish 1-2 times/month. A similar pattern was observed for aortic dissection. Regarding aortic aneurysm, both persons who seldom ate fish and those who ate fish 1-2 times/month had higher mortality (HR = 1.99; 95% CI, 0.90-4.40 and HR = 1.86; 95% CI, 0.87-3.98, respectively). CONCLUSIONS: Persons who seldom ate fish had higher mortality from aortic dissection, aneurysm, and total aortic diseases.

Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts.

BACKGROUND: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. METHODS: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models. RESULTS: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection. CONCLUSIONS: Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.

Changes in Smoking Status and Mortality From All Causes and Lung Cancer: A Longitudinal Analysis of a Population-based Study in Japan.

BACKGROUND: To update the findings of relative risk associated with smoking for all-cause mortality and that for lung cancer by considering longitudinal changes in smoking status during follow-up. METHODS: Data from the JPHC study of 98,747 middle-aged Japanese adults, which started in 1990-1993, were analyzed. The information on smoking status was obtained from three questionnaire surveys (baseline, the 5th year, and the 10th year after the start of follow-up). A Poisson regression model was used to investigate the impact of smoking on mortality from all causes and lung cancer using two approaches. Model 1 used information only from baseline, while model 2 used the updated smoking status from all three surveys. RESULTS: During the 15-year follow-up, 10,702 all-cause deaths (including 870 lung cancer cases) were identified. We compared the results obtained from two models. The relative risks associated with former smokers versus never smokers were 1.42 (95% confidence interval [CI], 1.31-1.54) among men and 1.46 (95% CI, 1.23-1.73) among women for all-cause mortality and 2.98 (95% CI, 2.09-4.24) among men and 1.83 (95% CI, 0.92-3.64) among women for lung cancer mortality, as determined using model 2. All of these were higher than the relative risks obtained from model 1. In addition, former smokers who had quit smoking due to disease during follow-up had a higher mortality risk than continuous smokers did in this study. CONCLUSIONS: The relative risks of all-cause mortality and mortality due to lung cancer among former smokers be higher than previously documented based on updated smoking status data from repeated surveys.

Consumption of red and processed meat and breast cancer incidence: A systematic review and meta-analysis of prospective studies.

Prior studies on red and processed meat consumption with breast cancer risk have generated inconsistent results. We performed a systematic review and meta-analysis of prospective studies to summarize the evidence regarding the relation of red meat and processed meat consumption with breast cancer incidence. We searched in MEDLINE and EMBASE databases through January 2018 for prospective studies that reported the association between red meat and processed meat consumption with incident breast cancer. The multivariable-adjusted relative risk (RR) was combined comparing the highest with the lowest category of red meat (unprocessed) and processed meat consumption using a random-effect meta-analysis. We identified 13 cohort, 3 nested case-control and two clinical trial studies. Comparing the highest to the lowest category, red meat (unprocessed) consumption was associated with a 6% higher breast cancer risk (pooled RR,1.06; 95% confidence intervals (95%CI):0.99-1.14; I2 = 56.3%), and processed meat consumption was associated with a 9% higher breast cancer risk (pooled RR, 1.09; 95%CI, 1.03-1.16; I2 = 44.4%). In addition, we identified two nested case-control studies evaluating the association between red meat and breast cancer stratified by N-acetyltransferase 2 acetylator genotype. We did not observe any association among those with either fast (per 25 g/day pooled odds ratio (OR), 1.18; 95%CI, 0.93-1.50) or slow N-acetyltransferase 2 acetylators (per 25 g/day pooled OR, 0.99; 95%CI, 0.91-1.08). In the prospective observational studies, high processed meat consumption was associated with increased breast cancer risk.

Circulating inflammatory markers and colorectal cancer risk: A prospective case-cohort study in Japan.

Blood levels of inflammation-related markers may reveal molecular pathways contributing to carcinogenesis. To date, prospective associations with colorectal cancer (CRC) risk have been based on few studies with limited sets of analytes. We conducted a case-cohort study within the Japan Public Health Center-based Prospective Study Cohort II, comparing 457 incident CRC cases during median 18 years follow-up with a random subcohort of 774 individuals. Baseline plasma levels of 62 cytokines, soluble receptors, acute-phase proteins, and growth factor markers were measured using Luminex bead-based assays. We estimated hazard ratios (HRs) associating each marker with CRC risk by Cox proportional hazards models adjusted for potential confounders. Subanalyses compared cases by years after blood draw (<5 vs. ≥5) and anatomical subsite (colon vs. rectum). Linear trends in quantiles of four C-C motif ligand (CCL) chemokines, one C-X-C motif ligand (CXCL) chemokine, and a soluble receptor were nominally associated with CRC risk based on ptrend < 0.05, but none met false discovery rate corrected statistical significance. HRs for the 4th vs. 1st quartile were: 1.69 for CCL2/MCP1, 1.61 for soluble tumor necrosis factor receptor 2, 1.39 for CCL15/MIP1D, 1.35 for CCL27/CTACK, 0.70 for CXCL6/GCP2 and 0.61 for CCL3/MIP1A. Among cases diagnosed 5+ years after enrollment, CCL2/MCP1, CCL3/MIP1A and CXCL6/GCP2 retained nominal statistical significance. There were no significant differences in associations between colon and rectum. Our findings implicate chemokine alterations in colorectal carcinogenesis, but require replication for confirmation. Noninvasive chemokine assays may have potential application in colorectal cancer screening and etiologic research.

Dietary patterns and prostate cancer risk in Japanese: the Japan Public Health Center-based Prospective Study (JPHC Study).

PURPOSE: The development of prostate cancer may be impacted by environmental factors, including diet. The aim of this study was to evaluate the association between dietary patterns and risk of prostate cancer in a large prospective cohort study among Japanese men. METHODS: A total of 43,469 men who participated in the Japan Public Health Center-based Prospective Study were followed from 1995 to 1998 to the end of 2012, during which 1,156 cases of prostate cancer were newly identified. Dietary intake was assessed using a validated food frequency questionnaire in the 5-year follow-up survey. RESULTS: Three major dietary patterns were derived using exploratory factors analysis: prudent, westernized, and traditional dietary patterns. The westernized dietary pattern was associated with a higher risk of total prostate cancer (HR: 1.22; 95% CI 1.00-1.49; p trend = 0.021), localized cancer (HR: 1.24; 95% CI 0.97-1.57; p trend = 0.045), and advanced cancer (HR: 1.23; 95% CI 0.82-1.84; p trend = 0.233). The prudent dietary pattern was associated with a lower risk of total and localized prostate cancer, with respective multivariable HRs for the highest and lowest quintiles of 0.71 (95% CI 0.50-1.02; p trend = 0.037) and 0.63 (95% CI 0.38-1.03; p trend = 0.048) among subjects detected by subjective symptoms. No association was found between the traditional dietary pattern and prostate cancer risk among our subjects. CONCLUSION: Our results suggest that a western-style diet may lead to a higher risk of prostate cancer in the total population, whereas the prudent diet contributes to a lower risk among subjects detected by subjective symptoms.

Plasma 25-hydroxyvitamin D concentration and subsequent risk of total and site specific cancers in Japanese population: large case-cohort study within Japan Public Health Center-based Prospective Study cohort.

OBJECTIVE: To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study. DESIGN: Nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort. SETTING: Nine public health centre areas across Japan. PARTICIPANTS: 3301 incident cases of cancer and 4044 randomly selected subcohort participants. EXPOSURE: Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference. MAIN OUTCOME MEASURE: Incidence of overall or site specific cancer. RESULTS: Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios. CONCLUSIONS: In this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites.

Risk of thyroid cancer in relation to height, weight, and body mass index in Japanese individuals: a population-based cohort study.

Greater height and body mass index (BMI) have been associated with an increased risk of thyroid cancer incidence in Western countries. However, few epidemiological studies have assessed the association between anthropometric factors, such as BMI, height, or weight, and thyroid cancer incidence in Asian populations. Using the population-based Japan Public Health Center-based prospective study database, we investigated the relationship between anthropometric factors and thyroid cancer incidence. Data on anthropometric factors were collected through a self-administered questionnaire at baseline. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards model, and the exposure level was categorized into quintiles. A total of 49,062 men and 53,661 women enrolled between 1990 and 1994 were included in our analyses, and 191 cases (37 in men and 154 in women) of thyroid cancer were identified, with 1,695,702 person-years of follow-up until 2010. Compared with the male group with height ≤160 cm, HRs of the male groups with height 165-168 cm and ≥169 cm were 3.92 (95% CI; 1.33-11.55, P = 0.013) and 4.24 (95% CI; 1.32-13.61, P = 0.015), respectively, and the HR per 5-cm increase in height was 1.12 (95% CI 1.06-1.18, P < 0.001). In contrast, the association between anthropometric features and the risk of thyroid cancer did not significantly differ among women. In this population, an increase in risk for increased height was observed in men, but no associations between anthropometric indexes and thyroid cancer risk were observed in women.

Cigarette smoking, alcohol drinking, and oral cavity and pharyngeal cancer in the Japanese: a population-based cohort study in Japan.

The effects of cigarette smoking and alcohol drinking on the incidence of oral cavity and pharyngeal cancer (OCPC) in the Asian population have been poorly understood. To assess the effects of cigarette smoking, alcohol drinking, and facial flushing response on incidence of OCPC, a total of 95 525 middle-aged and older eligible individuals were followed in a large-scale population-based cohort study in Japan from 1990 to 2010. In this study, the person-years of observation were 698 006 in men and 846 813 in women, and a total of 222 cases (men=160, women=62) of OCPC were newly diagnosed during the study period. A multivariate Cox proportional-hazards model was used to assess the incidence risk of OCPC and subsites by cigarette smoking and alcohol drinking. The result showed that cigarette smoking and regular alcohol drinking were associated significantly with the incidence of OCPC in men. Compared with nonsmokers and nondrinkers, current male smokers showed a hazard ratio (HR) of 2.37 [95% confidence interval (CI)=1.51-3.70] and regular male drinkers showed an HR of 1.82 (95% CI=1.20-2.76). Cigarette smoking also increased the risk of OCPC among male heavy alcohol drinkers (HR=4.05, 95% CI=2.31-7.11). However, there was no significant association between facial flushing response and OCPC. In conclusion, cigarette smoking and alcohol drinking are independent risk factors for OCPC and its subsites in the male Japanese population.

Development of a risk prediction model for lung cancer: The Japan Public Health Center-based Prospective Study.

Although the impact of tobacco consumption on the occurrence of lung cancer is well-established, risk estimation could be improved by risk prediction models that consider various smoking habits, such as quantity, duration, and time since quitting. We constructed a risk prediction model using a population of 59 161 individuals from the Japan Public Health Center (JPHC) Study Cohort II. A parametric survival model was used to assess the impact of age, gender, and smoking-related factors (cumulative smoking intensity measured in pack-years, age at initiation, and time since cessation). Ten-year cumulative probability of lung cancer occurrence estimates were calculated with consideration of the competing risk of death from other causes. Finally, the model was externally validated using 47 501 individuals from JPHC Study Cohort I. A total of 1210 cases of lung cancer occurred during 986 408 person-years of follow-up. We found a dose-dependent effect of tobacco consumption with hazard ratios for current smokers ranging from 3.78 (2.00-7.16) for cumulative consumption ≤15 pack-years to 15.80 (9.67-25.79) for >75 pack-years. Risk decreased with time since cessation. Ten-year cumulative probability of lung cancer occurrence estimates ranged from 0.04% to 11.14% in men and 0.07% to 6.55% in women. The model showed good predictive performance regarding discrimination (cross-validated c-index = 0.793) and calibration (cross-validated χ2 = 6.60; P-value = .58). The model still showed good discrimination in the external validation population (c-index = 0.772). In conclusion, we developed a prediction model to estimate the probability of developing lung cancer based on age, gender, and tobacco consumption. This model appears useful in encouraging high-risk individuals to quit smoking and undergo increased surveillance.

The association between plasma C-peptide concentration and the risk of prostate cancer: a nested case-control study within a Japanese population-based prospective study.

The association between plasma C-peptide concentration and prostate cancer is unclear. Inconsistency of results from previous studies motivates this study. Using the Japan Public Health Center-based Prospective study, 201 prostate cancer cases and 402 controls were matched by age, public health center area, residence, date and time of blood collection, and fasting duration before blood collection. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated by conditional logistic regression models. Out of 201 cases, 144 were localized and 48 were advanced. The overall association between median plasma C-peptide concentration and prostate cancer was not significant (OR for the highest tertile=0.81, 95% CI: 0.43-1.56, P-trend=0.54). Although stratification of prostate cancer by stage indicated different effects of plasma C-peptide on localized and advanced cases, there was no association between plasma C-peptide concentration and advanced prostate cancer (OR=2.82, 95% CI: 0.30-26.36 for the highest category, P-trend=0.37) and localized cases (OR=0.49, 95% CI: 0.23-1.04 for the highest category, P-trend=0.06) for patients fasting at the time of blood collection. The association between plasma C-peptide concentration and prostate cancer risk differed by cancer stage. Differentiation of localized and advanced prostate cancer cases is crucial when investigating the association between plasma C-peptide concentration and the risk of prostate cancer.

Menstrual and reproductive factors in the risk of thyroid cancer in Japanese women: the Japan Public Health Center-Based Prospective Study.

The aim of this study was to evaluate the associations between menstrual and reproductive factors and thyroid cancer risk among Japanese women. A total 54 776 women aged 40-69 years completed a self-administered questionnaire, which included menstrual and reproductive history. During 1990-2012, 187 newly diagnosed cases of thyroid cancer were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) for menstrual and reproductive factors and incidence of thyroid cancer were estimated using Cox proportional hazards regression. Postmenopausal women who had natural menopause were at reduced risk of thyroid cancer than premenopausal women in the age-area-adjusted model (HR: 0.62 per 1 year increase, 95% CI: 0.39-0.99), but this association was slightly attenuated and no longer statistically significant in the multivariable-adjusted model. On analysis by menopausal status, an inverse association between age at menarche and risk of thyroid cancer was observed for premenopausal women (HR: 0.83 per 1 year increase, 95% CI: 0.70-0.98, P trend=0.03), but not for postmenopausal women. The risk of thyroid cancer increased with surgical menopause compared with natural menopause (HR: 2.34, 95% CI: 1.43-3.84). Although increasing age at menopause and duration of fertility were associated with an increased risk of thyroid cancer, this association was not observed among postmenopausal women. This study confirmed that early age at menarche for premenopausal women and surgical menopause and late age at natural menopause for postmenopausal women were associated with the development of thyroid cancer. Our results support the hypothesis that exposure to estrogens increases the risk of thyroid cancer.

Body-Mass Index and Pancreatic Cancer Incidence: A Pooled Analysis of Nine Population-Based Cohort Studies With More Than 340,000 Japanese Subjects.

BACKGROUND: A high body mass index (BMI) has been proposed as an important risk factor for pancreatic cancer. However, this association of BMI with pancreatic cancer risk has not been confirmed in Asian populations. METHODS: We evaluated the association between BMI (either at baseline or during early adulthood) and pancreatic cancer risk by conducting a pooled analysis of nine population-based prospective cohort studies in Japan with more than 340,000 subjects. Summary hazard ratios (HRs) were estimated by pooling study-specific HRs for unified BMI categories with a random-effects model. RESULTS: Among Japanese men, being obese at baseline was associated with a higher risk of pancreatic cancer incidence (≥30 kg/m2 compared with 23 to <25 kg/m2, adjusted HR 1.71; 95% confidence interval [CI], 1.03-2.86). A J-shaped association between BMI during early adulthood and pancreatic cancer incidence was seen in men. In contrast, we observed no clear association among women, although there may be a positive linear association between BMI at baseline and the risk of pancreatic cancer (per 1 kg/m2, adjusted HR 1.02; 95% CI, 1.00-1.05). CONCLUSIONS: Pooling of data from cohort studies with a considerable number of Japanese subjects revealed a significant positive association between obesity and pancreatic cancer risk among men. This information indicates that strategies that effectively prevent obesity among men might lead to a reduced burden of pancreatic cancer, especially in Asian populations.

Coffee Consumption and Lung Cancer Risk: The Japan Public Health Center-Based Prospective Study.

BACKGROUND: Many epidemiological studies have indicated a positive association between coffee intake and lung cancer risk, but such findings were suggested to be confounded by smoking. Furthermore, only a few of these studies have been conducted in Asia. Here, we investigated the association between coffee intake and lung cancer risk in one of the largest prospective cohort studies in Japan. METHODS: We investigated the association of coffee drinking and subsequent incidence of lung cancer among 41,727 men and 45,352 women in the Japan Public Health Center-based Prospective Study using Cox proportional hazards regression, with adjustment for potential confounders and by strata of smoking status. Coffee and other dietary intakes were assessed once at baseline with a food frequency questionnaire (FFQ). RESULTS: During 1,481,887 person-years of follow-up between 1990 and 2011, a total of 1,668 lung cancer cases were identified. In a multivariate regression model, coffee consumption was not associated with risk of lung cancer (HR 1.16; 95% CI, 0.82-1.63; Ptrend = 0.285 for men and HR 1.49; 95% CI, 0.79-2.83; Ptrend = 0.942 for women). However, there was a significant increase in the risk for small cell carcinoma (HR 3.52; 95% CI, 1.49-8.28; Ptrend < 0.001). CONCLUSION: Our prospective study suggests that habitual consumption of coffee is not associated with an increased risk of lung cancer incidence, despite observing a significant increase in the risk for small cell carcinoma.

Impact of Alcohol Intake and Drinking Patterns on Mortality From All Causes and Major Causes of Death in a Japanese Population.

BACKGROUND: We examined the associations of alcohol consumption and liver holidays with all-cause mortality and with mortality due to cancer, heart disease, cerebrovascular disease, respiratory disease, and injury using a large-scale prospective study in Japan. METHODS: We followed 102,849 Japanese who were aged between 40 and 69 years at baseline for 18.2 years on average, during which 15,203 deaths were reported. Associations between alcohol intake and mortality risk were assessed using a Cox proportional hazards model, with analysis by the number of liver holidays (in which a person abstains from drinking for several days a week). RESULTS: A J-shaped association was observed between alcohol intake and total mortality in men (nondrinkers: reference; occasional drinkers: hazard ratio [HR] 0.74; 95% confidence interval [CI], 0.68-0.80; 1-149 g/week: HR 0.76; 95% CI, 0.71-0.81; 150-299 g/week: HR 0.75; 95% CI, 0.70-0.80; 300-449 g/week: HR 0.84; 95% CI, 0.78-0.91; 450-599 g/week: HR 0.92; 95% CI, 0.83-1.01; and ≥600 g/week: HR 1.19; 95% CI, 1.07-1.32) and in women (nondrinkers: reference; occasional: HR 0.75; 95% CI, 0.70-0.82; 1-149 g/week: HR 0.80; 95% CI, 0.73-0.88; 150-299 g/week: HR 0.91; 95% CI, 0.74-1.13; 300-449 g/week: HR 1.04; 95% CI, 0.73-1.48; and ≥450 g/week: HR 1.59; 95% CI, 1.07-2.38). In current drinkers, alcohol consumption was associated with a linear, positive increase in mortality risk from all causes, cancer, and cerebrovascular disease in both men and women, but not heart disease in men. Taking of liver holidays was associated with a lower risk of cancer and cerebrovascular disease mortality in men. CONCLUSIONS: Alcohol intake showed J-shaped associations with the risk of total mortality and three leading causes of death. However, heavy drinking increases the risk of mortality, which highlights the necessity of drinking in moderation coupled with liver holidays.

Dietary patterns and colorectal cancer risk in middle-aged adults: A large population-based prospective cohort study.

BACKGROUND & AIMS: A finding between dietary pattern and cancer may provide visions beyond the assessment of individual foods or nutrients. We examined the influence of dietary pattern with colorectal cancer (CRC) among a Japanese population. METHODS: A total of 93,062 subjects (43,591 men, 49,471 women) who participated in the Japan Public Health Center-based Prospective Study were followed from 1995-1998 to the end of 2012, during which 2482 cases of CRC (1514 men, 968 women) were newly identified. Dietary data was obtained from a validated food-frequency questionnaire between 1995 and 1998. RESULTS: Three dietary pattern was derived from principal components factor: prudent, westernized, and traditional pattern. After controlled for potential confounders, the prudent pattern showed a decreased association of CRC risk in men (HR for highest quintile vs lowest: 0.85; 95% CI: 0.72-1.00; P trend <0.05), slightly more strongly with distal colon cancer (P trend <0.05); but an increased risk of rectal cancer in women (P trend <0.05). The westernized pattern showed a significant positive linear trend for colon (P trend <0.05) and distal cancer (P trend <0.05) in women. There was no apparent association of traditional Japanese dietary pattern on the overall or any specific sites risk of CRC. CONCLUSIONS: A prudent dietary pattern showed an inverse association with CRC risk in men, and a westernized pattern was related with a higher risk of colon and distal cancer in women.

Smoking cessation and subsequent risk of cancer: A pooled analysis of eight population-based cohort studies in Japan.

BACKGROUND: Although East Asia is one of the largest tobacco-epidemic regions in the world, only a few prospective studies from Asia have investigated the impact of smoking and cessation of smoking on cancer. We aimed to assess the effect of cessation of smoking on the risk of cancer using eight population-based cohort studies in Japan. METHODS: We analyzed pooled data from eight population-based prospective cohort studies in Japan with more than 320,000 participants to assess the effect of smoking cessation on the risk of total cancers and smoking-related cancers. RESULTS: After adjustment for potential confounders, cancer risks in men with >21years of smoking cessation before baseline were found to decrease to the same level as never smokers for total cancer (never smokers: reference; former smokers with ≥21 years since smoking cessation: HR, 1.01; 95%CI: 0.91, 1.11). Even men who are heavy smokers (more than 20 pack-years) reported a reduced risk of total cancer (never smokers: reference; former smokers with ≥21 years since smoking cessation: HR, 1.06; 95%CI: 0.92, 1.23). In women, the risk of total cancer did not differ from that of never smokers after 11 years of smoking cessation before baseline (never smokers: reference; former smokers with ≥11 years since smoking cessation: HR, 0.96; 95%CI: 0.74, 1.23). CONCLUSIONS: Our study suggests that longer duration of smoking cessation may attenuate the risk of cancer in both men and women, and that even heavy smokers (more than 20 pack-years) were found to benefit from quitting smoking.

Perceived stress level and risk of cancer incidence in a Japanese population: the Japan Public Health Center (JPHC)-based Prospective Study.

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.

Estimation of lifetime cumulative incidence and mortality risk of gastric cancer.

OBJECTIVE: To estimate cumulative incidence and mortality risk for gastric cancer by risk category. METHODS: Risk was classified into four types according to the presence/absence of Helicobacter pylori infection and chronic atrophic gastritis: in order of lowest to highest risk, Group A: H. pylori(-) and atrophic gastritis(-); Group B: H. pylori(+) and atrophic gastritis(-); Group C:H. pylori(+) and atrophic gastritis(+); and, Group D: H. pylori(-) and atrophic gastritis(+). We used vital statistics for the crude all-cause and crude gastric cancer mortality rates in 2011 and data from population-based cancer registries (the Monitoring of Cancer Incidence in Japan) for gastric cancer incidence in 2011. For relative risk and prevalence, we used the results of a meta-analysis integrating previous studies and data from the Japan Public Health Center-based Prospective Study for the Next Generation, respectively (baseline survey 2011-16). We calculated the crude incidence and mortality rates and estimated the cumulative risk using a life-table method. RESULTS: The estimated lifetime cumulative incidence risk was 11.4% for men and 5.7% for women. The estimated risk for Groups A, B, C and D was 2.4%, 10.8%, 26.7% and 35.5% for men, and 1.2%, 5.5%, 13.5% and 18.0% for women, respectively. Similarly, the estimated lifetime cumulative mortality risk was 3.9% for men and 1.8% for women. The estimated risk of mortality for Groups A, B, C and D was 0.8%, 3.6%, 9.0% and 12.0% for men, and 0.4%, 1.7%, 4.2% and 5.7% for women, respectively. CONCLUSIONS: Our results may be useful for designing individually tailored prevention programs.