JPHC Study Research Articles

Association between fish and shellfish consumption, n-3 polyunsaturated fatty acids, and gastric cancer risk: the Japan Public Health Center-based Prospective Study

PurposeFish and shellfish consumption is suggested to be a cancer-protective factor. However, studies investigating this association for gastric cancer, especially considering Helicobacter pylori (H. pylori) and atrophic gastritis (AG), are limited. We investigated gastric cancer risk associated with fish, shellfish, and n-3 polyunsaturated fatty acids (n-3 PUFAs) consumption among Japanese adults.Methods90,504 subjects enrolled in the Japan Public Health Center-based Prospective Study (JPHC Study) were followed until December 2013. Dietary intake data were collected using a food frequency questionnaire. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for gastric cancer risk associated with fish and shellfish consumption and marine n-3 PUFAs (sum of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA)) using Cox proportional hazards models. Among those with avaliable data, we conducted a subgroup analysis taking H. pylori infection and AG status into consideration.ResultsThere were 2,701 gastric cancer cases during an average of 15 years of follow-up. We observed an increased gastric cancer risk for salted fish consumption for men [HR for fifth quintile versus first quintile 1.43 (95% CI 1.18–1.75)] and for women [HR 1.33 (95% CI 1.00–1.77)]. We observed a weak risk reduction trend for women as the intake of marine n-3 PUFAs increased (p-trend:0.07). When we included H. pylori infection and atrophic gastritis status in the analysis, the associations diminished.ConclusionOur results suggest that salted fish increases gastric cancer risk for men and women, while marine n-3 PUFAs marginally decreases this risk among women in Japan.

Bowel movement frequency, stool consistency, and risk of disabling dementia: a population-based cohort study in Japan

ObjectivesThis population-based study aimed to evaluate the association between bowel habits from midlife and dementia. Study designThis was a cohort study using certification records for national long-term care insurance in Japan. MethodsParticipants aged 50 to 79 years who reported bowel habits from eight districts within the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from 2006 to 2016 for incident dementia. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for men and women separately using Cox proportional hazards models accounting for various lifestyle factors and medical histories. ResultsAmong 19,396 men and 22,859 women, 1889 men and 2685 women were diagnosed with dementia. In men, the multivariable-adjusted HRs compared with bowel movement frequency (BMF) of once/day were 1.00 (95% CI: 0.87–1.14) for twice/day or more, 1.38 (1.16–1.65) for 5–6 times/week, 1.46 (1.18–1.80) for 3–4 times/week, and 1.79 (1.34–2.39) for <3 times/week (P for trend <0.001). In women, the corresponding HRs were 1.14 (0.998–1.31), 1.03 (0.91–1.17), 1.16 (1.01–1.33), and 1.29 (1.08–1.55) (P for trend = 0.043). Harder stool was associated with higher risk (P for trend: 0.0030 for men and 0.024 for women), with adjusted HRs compared to normal stool of 1.30 (1.08–1.57) for hard stool and 2.18 (1.23–3.85) for very hard stool in men, and 1.15 (1.002–1.32) and 1.84 (1.29–2.63) in women. ConclusionsLower BMF and harder stool were each associated with higher risk of dementia.

Lack of significant associations between single nucleotide polymorphisms in LPAL2-LPA genetic region and all cancer incidence and mortality in Japanese population: The Japan public health center-based prospective study

BackgroundHigh lipoprotein (a) level is an established cardiovascular risk, but its association with non-cardiovascular diseases, especially cancer, is controversial. Serum lipoprotein (a) levels vary widely by genetic backgrounds and are largely determined by the genetic variations of apolipoprotein (a) gene, LPA. In this study, we investigate the association between SNPs in LPA region and cancer incidence and mortality in Japanese. MethodsA genetic cohort study was conducted utilizing the data from 9923 participants in the Japan Public Health Center-based Prospective Study (JPHC Study). Twenty-five SNPs in the LPAL2-LPA region were selected from the genome-wide genotyped data. Cox regression analysis adjusted for the covariates and competing risks of death from other causes, were used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of overall and site-specific cancer incidence and mortality, for each SNP. ResultsNo significant association was found between SNPs in the LPAL2-LPA region and cancer incidence or mortality (overall/site-specific cancer). In men, however, HRs for stomach cancer incidence of 18SNPs were estimated higher than 1.5 (e.g., 2.15 for rs13202636, model free, 95%CI: 1.28–3.62) and those for stomach cancer mortality of 2SNPs (rs9365171, rs1367211) were estimated 2.13 (recessive, 95%CI:1.04–4.37) and 1.61 (additive, 95%CI: 1.00–2.59). Additionally, the minor allele for SNP rs3798220 showed increased death risk from colorectal cancer (CRC) in men (HR: 3.29, 95% CI:1.59 – 6.81) and decreased CRC incidence risk in women (HR: 0.46, 95%CI: 0.22–0.94). Minor allele carrier of any of 4SNPs could have risk of prostate cancer incidence (e.g., rs9365171 dominant, HR: 1.71, 95%CI: 1.06–2.77). ConclusionsNone of the 25 SNPs in the LPAL2-LPA region was found to be significantly associated with cancer incidence or mortality. Considering the possible association between SNPs in LPAL2-LPA region and colorectal, prostate and stomach cancer incidence or mortality, further analysis using different cohorts is warranted.

Exploratory Research on Determinants of Place of Death in a Large-scale Cohort Study: The JPHC Study.

The place of death and related factor, such as diseases, symptoms, family burden, and cost, has been examined, but social background and lifestyle were not considered in most studies. Here, we assessed factors that are associated with the place of death using the largest cohort study in Japan. A total of 17,781 deaths from the cohort study were assessed. The study database was created from the Japan Public Health Center-based Prospective Study (JPHC Study), in which demographic data were collected from Japanese Vital Statistics. Adjusted odds ratios for home death were calculated using logistic regression. Multivariate analysis adjusted for various factors showed that unmarried status (odds ratio [OR] 2.4; 95% confidence interval [CI], 2.0-2.9), unemployed male (OR 1.3; 95% CI, 1.1-1.5), and high drinking level in male (OR 1.3; 95% CI, 1.1-1.6) were associated with home death. Regarding the cause of death, cardiovascular disease (OR 3.3; 95% CI, 2.9-3.8), cerebrovascular disease (OR 1.9; 95% CI, 1.6-2.2), and external factors (OR 4.1; 95% CI, 3.5-4.8) were significantly associated with home death, compared with cancer. The risk of death at home was significantly higher among unmarried subjects stratified by cause of death (cardiovascular disease: OR 3.2; 95% CI, 2.2-4.7; cerebrovascular disease: OR :5.1; 95% CI, 2.9-9.1; respiratory disease: OR 3.4; 95% CI, 1.6-7.6; and external factors: OR 2.3; 95% CI, 1.4-3.7), but for cancer, the risk of death at home tended to be higher among married participants. This study found that various factors are associated with home death using the largest cohort study in Japan. There is a high possibility of home deaths in people with fewer social connections and in those with diseases leading to sudden death.

Alcohol consumption from midlife and risk of disabling dementia in a large population-based cohort study in Japan.

The association between alcohol consumption and dementia in Japanese is poorly understood, and use of single-point alcohol assessment may cause measurement error. We explored this association in Japanese using repeated alcohol assessments. Participants in the Japan Public Health Center-based Prospective Study (JPHC Study) since 1990 and who were alive in 2006 were followed from 2006 until 2016 for dementia ascertainment. Disabling dementia was identified through long-term care insurance records. Alcohol consumption was assessed at the 5-year questionnaire survey (1995-1999) and drinking patterns were assessed on repeated follow-up (2000-2003). We performed Cox proportional hazards models with age as the time-scale with adjustment for various lifestyle factors and medical history using light consumption (<75g ethanol/week, hereinafter "g") as reference. Analysis considering death as a competing risk was also conducted. Among 42,870 participants aged 54-84years, 4802 cases of disabling dementia were newly diagnosed. Average years from alcohol assessment until dementia incidence was 14.9years. Non-drinkers and regular drinkers with ≥450g at 5years had adjusted HRs (95% CI) of 1.29 (1.12-1.47) and 1.34 (1.12-1.60). Patterns of long-term abstinence, former drinking, and regular heavy weekly consumption of ≥450g showed increased adjusted HRs of 1.61 (1.28-2.03), 2.54 (1.93-3.35), and 1.96 (1.49-2.59), respectively. Competing risk analysis yielded similar results. In Japanese, non-drinking and regular weekly consumption of ≥450g from midlife were associated with high risk of disabling dementia compared with light drinking.

Green tea and coffee consumption and risk of kidney cancer in Japanese adults

The study aimed to evaluate the association between green tea and coffee consumption and the risk of kidney cancer using data from a large prospective cohort study in Japan (the Japan Public Health Center-based Prospective Study: JPHC Study). A total of 102,463 participants aged 40–69 were followed during 1,916,421 person-years (mean follow-up period, 19 years). A total of 286 cases of kidney cancer (199 in men, 87 in women) were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) while adjusting for potential confounders. No statistically significant association between green tea intake and kidney cancer risk was found in the total population. Among women who consumed more than five cups of green tea per day, a statistically significant decreased risk was shown with a HR of 0.45 (95% CI: 0.23–0.89), compared to women who rarely consumed green tea. For coffee consumption, the association of kidney cancer risk was not statistically significant. This large prospective cohort study indicated green tea intake may be inversely associated with kidney cancer risk in Japanese adults, particularly in Japanese women.

Increased risk of death from pneumonia among cancer survivors: A propensity score-matched cohort analysis.

The repeated global pandemic of the new virus has led to interest in the possibility of severe pneumonia among cancer patients and survivors. Here, we aimed to assess the association between incident cancer and risk of death from pneumonia in Japanese in a large population-based cohort study. We used the data from The Japan Public Health Center-based Prospective Study (JPHC Study), which enrolled subjects aged 40 to 69 between 1990 and 1994 and followed their cancer incidence and mortality until 2013. After identifying 103,757 eligible subjects for analysis and imputing missing data on covariates by the chained equations approach, we conducted propensity score-matched analysis for 1:4 matching, leaving 14,520 cases diagnosed with cancer and 48,947 controls without cancer during the study period for final analysis. A Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and corresponding confidence interval (CI) for the risk of death from pneumonia with comparison of cancer cases and cancer-free controls. Compared to cancer-free individuals, risk of death from pneumonia was significantly higher among those who had any diagnosed cancer (HR, 1.41; 95%CI, 1.08-1.84); those within 1year of diagnosis (HR, 23.0; 95% CI, 2.98-177.3); within 1 to <2 years (HR, 3.66; 95% CI, 1.04-12.9); and those with regional spread or distant metastatic cancer at initial diagnosis (HR, 2.01; 95% CI, 1.26-3.21). A history of lung, oesophageal, and head and neck cancer conferred the higher risk among site-specific cancers. We found a positive association between incident cancer and risk of death from pneumonia in this study. These results imply the possibility that the immunocompromised status and respiratory failure due to antitumor treatment may have resulted in a more severe outcome from pneumonia among cancer survivors than the general population.

Current status of awareness, knowledge, beliefs, and behavioral intentions regarding the Japanese physical activity guidelines and their relationship with physical activity and sedentary behavior

Objective This study clarified the current status of awareness, knowledge, beliefs, and behavioral intentions regarding the Japanese physical activity guidelines (Active Guide) and their relationship with physical activity, sedentary behavior, and the participants' characteristics.Methods A cross-sectional study was conducted with 7,000 participants aged 20-69 years registered with an online survey company. Awareness, knowledge, beliefs, and behavioral intentions regarding the Active Guide were examined. Awareness was assessed by unprompted and prompted recall. Knowledge was assessed by numerical responses to "the recommended daily activity time (18-64 years/65 years and older)" and "physical activity time to be increased (plus-ten)," respectively. To survey the beliefs and behavioral intentions, we created a 5-point scale for the Active Guide. For physical activity, the amount of moderate-to-vigorous intensity physical activity was calculated from the Japan Public Health Center-based prospective Study (JPHC study) questionnaire. Physical activity level was calculated from the standard specific medical checkup and health guidance questionnaire. For sedentary behavior, the Japanese version of the International Physical Activity Questionnaire (IPAQ) was used. The dependent variables were awareness, knowledge, beliefs, and behavioral intentions. The independent variables were physical activity, sedentary behavior, and the participants' characteristics (gender, age, body mass index, marital status, educational background, work status, and household income). After descriptive statistics were measured, a logistic regression analysis was performed to examine the associations.Results Unprompted and prompted recall of the Active Guide were 1.7% and 5.3-13.4%, respectively. Those with knowledge of it scored 37.2%, 7.0%, 24.8%, and 2.6% for recommended daily activity time (18-64 years), daily physical activity time (65 years and older), plus-ten, and all three items answered correctly, respectively. The median (interquartile range) score of the beliefs was 21 (16-25) points (32-point scale). Those with behavioral intentions scored 51.4% for "recommended daily activity" and 66.9% for "plus-ten." Logistic regression analysis showed that awareness, knowledge, beliefs, and behavioral intentions were positively associated with moderate-to-vigorous intensity physical activity and level. The results were inconsistent for sedentary behavior. Although personal characteristics differed based on assessment item, they were mainly associated with age, education level, employment, and household income.Conclusions This study revealed that the number of people who had awareness and knowledge of the Active Guide remained low. Those with awareness, knowledge, beliefs, and behavioral intentions were more physically active. However, the results for sedentary behavior were not consistent. Hence, further research is required to understand this tendency. A future longitudinal study is also required.

Association of Plasma Iron Status with Subsequent Risk of Total and Site-Specific Cancer: A Large Case-Cohort Study within JPHC Study.

High ferritin and low hepcidin levels in the plasma were associated with increased liver cancer risk. Evaluating iron metabolism including hepcidin levels may help identify people with high liver cancer risk.

Prediagnostic plasma polyphenol concentrations and colon cancer risk: The JPHC nested case–control study

Epidemiological studies that assessed the associations between dietary polyphenol intakes and colon cancer risk have reported largely null results, possibly due to measurement error associated with dietary assessment. We adopted an objective approach by measuring prediagnostic plasma concentrations of 35 polyphenols and assessing associations with colon cancer risk. We conducted a nested-case control study within the Japan Public Health Center-based prospective study (JPHC Study) utilizing plasma samples collected at the time of a five-year follow-up survey between 1995 and 1999. We identified colon cancer cases who developed cancer during the follow-up from the time of blood collection. Controls were matched by age, sex, area code, population size of the area, season of blood collection, year of blood collection, and duration of fasting time before the blood collection. Prediagnostic concentrations of 35 polyphenols from 375 incident colon cancer cases (followed until 2012) and 710 matched controls were measured by tandem mass spectrometry coupled with ultra-high-pressure liquid chromatography. We used multivariable conditional logistic regression models adjusted for established colon cancer risk factors to estimate odds ratios (ORs) and 95% confidence intervals (CIs). In sexes combined log2-transformed multivariable models, circulating levels of 3,4-dihydroxyphenylpropionic acid (P=0.02), ferulic acid (P=0.02), and caffeic acid (P=0.03) were inversely, and 3-hydroxybenzoic acid (P=0.03) was positively, associated with colon cancer risk. For men only, circulating levels of 3,4-dihydroxyphenylpropionic acid was inversely, and 3,5-dihydroxyphenylpropionic acid, gallic acid, (+)-epigallocatechin, 3-hydroxybenzoic acid, and epicatechin were positively, associated with colon cancer risk. In women, plasma caffeic acid and ferulic acid concentration were inversely associated with colon cancer risk. However, all these associations were nonsignificant after adjustment for multiple comparisons. The remaining polyphenols were not associated with colon cancer risk. Coffee-derived 3,4-dihydroxyphenylpropionic acid, ferulic acid, and caffeic acid concentrations were inversely associated with colon cancer risk although the association were nonsignificant after adjustment for multiple comparisons. These results support a possible role of coffee polyphenols in preventing colorectal cancer.

The association between midlife living arrangement and psychiatrist-diagnosed depression in later life: who among your family members reduces the risk of depression?

This study investigates the longitudinal association between living arrangements and psychiatrists’ diagnosis of depression in the general population. In 1990, 1254 Japanese men and women aged 40–59 years were enroled and completed questionnaires on the living arrangement in the Japan Public Health Center-based Prospective Study (JPHC Study) and participated in a mental health screening (2014–2015). The study diagnosed a major depressive disorder (MDD) assessed by well-trained certified psychiatrists through medical examinations. During the follow-up, a total of 105 participants (36 men and 69 women) aged 64–84 years were diagnosed with MDD by psychiatrists. Living with a child (ren) was associated with a reduced risk of MDD for men but not for women; the respective multivariable ORs (95% CIs) were 0.42 (0.19–0.96) and 0.59 (0.32–1.09). These associations remained unchanged after adjusting for living with spouse and parent(s). In conclusion, living with a child (ren) was associated with a reduced risk of MDD in men, suggesting the role of a child (ren) in the prevention of MDD.

Long-term exposure to fine particle matter and all-cause mortality and cause-specific mortality in Japan: the JPHC Study

BackgroundMany 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 <2.5 µg/m3 (PM2.5) and mortality in a Japanese cohort with a relatively low exposure level.MethodsThe 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.ResultsAverage 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.ConclusionsWe 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.

COT-6 Body mass index and height in relation to brain tumor risk in a Japanese population

Purpose: Because the prognosis of the malignant brain tumor including glioblastoma is extremely worse than other cancer, it is important to clarify the preventive factors of the brain tumor in the prospective cohort study. In the Japanese epidemiologic study of the brain tumor, the report of the prospective cohort study has not been accomplished. Therefore, we have reported the study in recent years from a multipurpose cohort study (Japan Public Health Center-based Prospective Study: JPHC study) that the national cancer center was mainly conducted. This prospective study investigated the association between height and BMI (Body mass index) and brain tumor risk in an Asian population, whose distribution of anthropometric data differs from Westerners. Methods: A total of 106,324 subjects (50,438 men and 55,886 women) enrolled in JPHC Study, was followed from 1990. We divided participants into 5 categories based on the distribution of BMI as <18.5, 18.5- <23, 23- <25, 25- <27.5, and >-27.5 Kg/m2. We used the Cox proportional hazards regression model and estimated brain tumor incidence by gender and tumor subtype, with adjustment for potential confounding variables; age, sex, pack-years of cigarette smoking, alcohol intake, coffee intake, green tea intake, past history of allergy and past history of diabetes mellitus.Results: During an average follow-up of 18.1 years, 157 incident cases of brain tumor were newly identified, included glioma (n=60), meningioma (n =51), lymphoma(n=9), schwannoma(n=3), pituitary adenoma(n=2), and others(n=32). Higher BMI was significantly positively associated with the risk of brain tumor. This positive association of BMI was stronger in men and for meningioma in subgroup analyses. In contrast, height showed no clear association with brain tumor risk. Conclusion: Higher BMI was associated with an increased risk of brain tumor, in particular of meningioma, and among men.Full article has been published annals of epidemiology.

Alcohol consumption, tobacco smoking, and subsequent risk of renal cell carcinoma: The JPHC study.

The effects of alcohol consumption and tobacco smoking on renal cell carcinoma (RCC) incidence have not been well‐investigated in Asian populations. Here, we evaluated these effects in a large Japanese prospective cohort. We collected data on eligible participants in the Japan Public Health Center‐based Prospective Study, and undertook multivariable‐adjusted Cox proportional hazards regression to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of RCC incidence. We identified 340 cases (230 men and 110 women) among the 105 663 eligible participants (50 262 men and 55 741 women), who were followed for an average of 19.1 years, with a cumulative total of 2 020 364 person‐years. A slightly inverse but nonsignificant association was observed between alcohol drinking and RCC incidence. In contrast, the risk of RCC was increased in those with heavy smoking (≥40 pack‐years) when men and women were combined (HR 1.50; 95% CI, 1.01‐2.25). We identified no significant association between alcohol consumption and RCC incidence. In contrast, heavy smoking (≥40 pack‐years) was associated with a significant increase in incidence.

Peanut Consumption and Risk of Stroke and Ischemic Heart Disease in Japanese Men and Women: The JPHC Study.

Several prospective cohort studies and a randomized clinical trial have shown the beneficial effects of peanut consumption on cardiovascular disease and its risk factors. We examined the association between peanut consumption and risk of cardiovascular disease in Japanese men and women. We analyzed data of 74 793 participants aged 45 to 74 years who completed a lifestyle questionnaire including the validated food frequency questionnaire in the Japan Public Health Center–based Prospective Study. They were followed up from 1995 to 2009 for cohort I and from 1998 to 1999 to 2012 for cohort II. Peanut consumption was calculated from the food frequency questionnaire, and the end points were incidence of stroke, ischemic heart disease, and cardiovascular disease (stroke and ischemic heart disease). During a median follow-up of 14.8 years, 3,599 strokes and 849 ischemic heart diseases were reported. Higher peanut consumption was associated with reduced risks of total stroke, ischemic stroke, and cardiovascular disease among men and women. The multivariable hazard ratios (95% CIs) for the highest versus lowest quartiles of peanut consumption after adjustment for age, sex, public health center, smoking, alcohol consumption, perceived stress level, physical activity, vegetable, fruit, fish, soy, sodium and total energy intakes, body mass index, history of hypertension, history of diabetes, and cholesterol-lowering drug were 0.84 (0.77–0.93, P for trend=0.002) for total stroke, 0.80 (0.71–0.90, P for trend=0.002) for ischemic stroke, 0.93 (0.79–1.08, P for trend=0.27) for hemorrhagic stroke, 0.97 (0.80–1.17, P for trend=0.81) for ischemic heart disease and 0.87 (0.80–0.94, P for trend=0.004) for cardiovascular disease, and these associations were similarly observed in both sexes. Higher peanut consumption was associated with reduced risk of stroke, especially ischemic stroke, but not ischemic heart disease in Japanese men and women.

Prediagnostic circulating inflammation-related biomarkers and gastric cancer: A case-cohort study in Japan

Gastric cancer is preceded by a chronic inflammatory process. Circulating levels of inflammation-related markers may reveal molecular pathways contributing to cancer development. Our study evaluated risk associations of gastric cancer with a wide range of systemic soluble inflammation and immune-response proteins. We performed a case-cohort analysis within the JPHC Study II, including a subcohort of 410 participants selected randomly within defined age and sex groups, and 414 individuals with incident gastric cancer. Ninety-two biomarkers were measured in baseline plasma using proximity extension assays. Gastric cancer multivariable hazard ratios were calculated for two to four quantiles used as ordinal variables of each biomarker by Cox proportional hazards regression models with age as the time metric. Of 73 evaluable biomarkers, three (CCL11, CCL20 and IL17C) were associated with increased gastric cancer risk and two (CCL23 and MMP1) with reduced cancer risk (Ptrends < 0.05). However, no association was statistically significant after a false discovery rate correction. This study largely expands the range of inflammation molecules evaluated for gastric cancer risk but failed to identify novel associations with this neoplasia.

The Association Between Habitual Sleep Duration and Mortality According to Sex and Age: The Japan Public Health Center-based Prospective Study.

BackgroundShort and long sleep durations are associated with mortality outcomes. The association between sleep duration and mortality outcomes may differ according to sex and age.MethodsParticipants of the Japan Public Health Center-based prospective study (JPHC Study) were aged 40–69 years and had completed a detailed questionnaire on lifestyle factors. Sex- and age-stratified analyses on the association between habitual sleep duration and mortality from all-causes, cardiovascular diseases (CVD), cancer and other causes included 46,152 men and 53,708 women without a history of CVD or cancer. Cox proportional hazards regression models, adjusted for potential confounders, were used to determine hazard ratios and 95% confidence intervals.ResultsMean follow-up time was 19.9 years for men and 21.0 years for women. In the multivariable sex-stratified models, some categories of sleep durations ≥8 hours were positively associated with mortality from all-causes, CVD, and other causes in men and women compared with 7 hours. The sex- and age-stratified analyses did not reveal any major differences in the association between sleep duration and mortality outcomes in groups younger and older than 50 years of age. The only exception was the significant interaction between sleep duration and age in women for mortality from other causes.ConclusionsSleep durations ≥8 hours are associated with mortality outcomes in men and women. Age may be an effect modifier for the association between sleep duration and mortality from other causes in women.

日本の運動疫学コホート（6） 多目的コホート研究 The Japan Public Health Center-based prospective Study (JPHC Study)

日本の運動疫学コホート（6） 多目的コホート研究 The Japan Public Health Center-based prospective Study (JPHC Study)

Fermented and nonfermented soy foods and the risk of breast cancer in a Japanese population-based cohort study.

BackgroundAlthough preclinical studies suggest that fermented soy foods may have a protective effect against breast cancer, no prospective cohort studies have examined this association.ObjectiveOur study examined the association between fermented and nonfermented soy food intake and breast cancer risk using a population‐based prospective cohort study in Japan.MethodsWe included a total of 47,614 women aged 45–74 years in an analysis of the Japan Public Health Center‐based Prospective Study (JPHC Study). A validated food frequency questionnaire (FFQ) was used for the assessment of dietary intake. Breast cancer incidence was analyzed by multivariate Cox proportional hazards regression models.ResultsDuring an average of 15.5 years of follow‐up, 825 breast cancer cases were newly identified. We found no association of intake of soy foods with breast cancer risk, regardless of fermentation, with multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest quartiles of fermented and nonfermented soy food intake of 0.94 (0.67, 1.32) and 1.15 (0.85, 1.57) compared with the lowest quartile (p for trend = 0.305 and 0.393). Unlike nonfermented soy, higher intake of fermented soy foods was associated with a significant decrease in the risk of nonlocalized breast cancer. The HR and 95% CI in the highest compared to lowest intake category of fermented soy foods was 0.53 (0.28, 0.99) versus nonfermented soy foods 0.85 (0.51, 1.42) (p for trend = 0.026 and 0.797).ConclusionsOur analyses showed that fermented soy foods had no association with overall breast cancer but may be associated with decreased risk of nonlocalized breast cancer.

Comparison between the impact of fermented and unfermented soy intake on the risk of liver cancer: the JPHC Study.

The aim of this study was to compare the impact of fermented and unfermented soy intake, based on the following soy-derived products: tofu, soymilk, natto, and miso, on the risk of liver cancer among Japanese adults. 75,089 Participants of the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from the time of the 5-year follow-up questionnaire until the end of 2012-2013. Subjects with available data on hepatitis B virus (HBV) and hepatitis C virus (HCV) infection status from blood samples (n = 14,016) and those who were anti-HCV antibody (anti-HCV) or hepatitis B virus antigen (HBsAg) positive (n = 1033) were also analyzed separately. Cox proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). During 1,145,453 person-years, 534 newly diagnosed cases of liver cancer were identified in the JPHC Study. For miso intake among men, the multivariate-adjusted highest versus lowest quartile HR was 0.65 (95% CI, 0.48-0.89); p for trend = 0.006. Results were similar in those who were anti-HCV or HBsAg positive, 0.24 (0.08-0.70); p for trend = 0.004 highest versus lowest tertile. For the sub-analysis among only participants with known hepatitis infection status and HCV and HBsAg adjustment, a similar association was observed. In the multivariate complete cohort analysis, among women, the highest intake of fried tofu was inversely associated with the risk of liver cancer, HR = 0.45 (0.26-0.80); p for trend = 0.014. We observed no association between total soy intake, fermented and unfermented, and risk of liver cancer, and only an inverse association between miso intake and liver cancer among men.