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

PURPOSE: Fish 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. METHODS: 90,504 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. RESULTS: There 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. CONCLUSION: Our 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.

Association of sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression: A five-year cohort study.

BACKGROUND & AIMS: Evidence on the impact of beverage consumption on depression is limited in the Asian population. Specifically, there is little information available on vegetable and fruit juices, while whole vegetables and fruits are reportedly protective against depression. Furthermore, evidence is scarce in differentiating the impacts of sweetened and black coffee. We aimed to examine the association of the consumption of total sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression in a general population sample. METHODS: We studied individuals without a history of cancer, myocardial infarction, stroke, diabetes, or depression at baseline in 2011-2016, with a five-year follow-up. We used Poisson regression models and the g-formula, thereby calculating the risk difference (RD) for depression. Multiple sensitivity analyses were conducted. Missing data were handled using random forest imputation. We also examined effect heterogeneity based on sex, age, and body mass index by analyzing the relative excess risk due to interaction and the ratio of risk ratios. RESULTS: In total, 94,873 individuals were evaluated, and 80,497 completed the five-year follow-up survey for depression. Of these, 18,172 showed depression. When comparing the high consumption group with the no consumption group, the fully adjusted RD (95% CI) was 3.6% (2.8% to 4.3%) for total sugary drinks, 3.5% (2.1% to 4.7%) for carbonated beverages, 2.3% (1.3% to 3.4%) for vegetable juice, 2.4% (1.1% to 3.6%) for 100% fruit juice, and 2.6% (1.9% to 3.5%) for sweetened coffee. In contrast, the fully adjusted RD (95% CI) was -1.7% (-2.6% to -0.7%) for black coffee. The fully adjusted RD for green tea did not reach statistical significance. The results were robust in multiple sensitivity analyses. We did not find substantial effect heterogeneity based on sex, age, and body mass index. CONCLUSIONS: Total sugary drinks, carbonated beverages, vegetable and fruit juices, and sweetened coffee may increase the risk of depression, whereas black coffee may decrease it.

Family history and gastric cancer incidence and mortality in Asia: a pooled analysis of more than half a million participants.

BACKGROUND: The family history of gastric cancer holds important implications for cancer surveillance and prevention, yet existing evidence predominantly comes from case-control studies. We aimed to investigate the association between family history of gastric cancer and gastric cancer risk overall and by various subtypes in Asians in a prospective study. METHODS: We included 12 prospective cohorts with 550,508 participants in the Asia Cohort Consortium. Cox proportional hazard regression was used to estimate study-specific adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between family history of gastric cancer and gastric cancer incidence and mortality, then pooled using random-effects meta-analyses. Stratified analyses were performed for the anatomical subsites and histological subtypes. RESULTS: During the mean follow-up of 15.6 years, 2258 incident gastric cancers and 5194 gastric cancer deaths occurred. The risk of incident gastric cancer was higher in individuals with a family history of gastric cancer (HR 1.44, 95% CI 1.32-1.58), similarly in males (1.44, 1.31-1.59) and females (1.45, 1.23-1.70). Family history of gastric cancer was associated with both cardia (HR 1.26, 95% CI 1.00-1.60) and non-cardia subsites (1.49, 1.35-1.65), and with intestinal- (1.48, 1.30-1.70) and diffuse-type (1.59, 1.35-1.87) gastric cancer incidence. Positive associations were also found for gastric cancer mortality (HR 1.30, 95% CI 1.19-1.41). CONCLUSIONS: In this largest prospective study to date on family history and gastric cancer, a familial background of gastric cancer increased the risk of gastric cancer in the Asian population. Targeted education, screening, and intervention in these high-risk groups may reduce the burden of gastric cancer.

Importance of circulating leptin and adiponectin in the causal pathways between obesity and the development of colorectal cancer in Japanese men.

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

Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium.

There has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two-stage meta-analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person-years]), follow-up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person-years]), follow-up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two-stage meta-analytic approach showed similar results. This paper adds important population-based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta-analysis across studies with large number of subjects makes the results robust.

Dietary Fiber Intake and Risk of Advanced and Aggressive Forms of Prostate Cancer: A Pooled Analysis of 15 Prospective Cohort Studies.

BACKGROUND: Evidence of an association between dietary fiber intake and risk of advanced and aggressive forms of prostate cancer (PC) and PC mortality is limited. OBJECTIVE: To examine associations between intakes of dietary fiber overall and by food source and risk of advanced and aggressive forms of PC. DESIGN: Pooled analysis of the primary data in 15 cohorts in three continents. Baseline dietary fiber intake was assessed using a validated food frequency questionnaire or diet history in each study. PARTICIPANTS/SETTING: 842,149 men were followed for up to 9-22 years between 1985-2009 across studies. MAIN OUTCOME MEASURES: The primary outcome measures were advanced (stage T4, N1, or M1 or PC mortality), advanced restricted (excluded men with missing stage and those with localized PC who died of PC), high grade (Gleason score ≥8 or poorly differentiated/undifferentiated) PC, and PC mortality. STATISTICAL ANALYSIS: Study-specific multivariable hazard ratios (MVHR) were calculated using Cox proportional hazards regression and pooled using random effects models. RESULTS: Intake of dietary fiber overall, from fruits, and from vegetables was not associated with risk of advanced (n=4,863), advanced restricted (n=2,978), or high-grade PC (n=9,673) or PC mortality (n=3,097). Dietary fiber intake from grains was inversely associated with advanced PC (MVHR comparing the highest vs. lowest quintile=0.84, 95% confidence interval [CI] 0.76-0.93), advanced restricted PC (MVHR=0.85, 95%CI 0.74-0.97), and PC mortality (MVHR=0.78, 95%CI 0.68-0.89); statistically significant trends were noted for each of these associations (p≤0.03), while a null association was observed for high grade PC for the same comparison (MVHR=1.00, 95%CI 0.93-1.07). The comparable results were 1.06 (95%CI 1.01-1.10, p-value, test for trend=0.002) for localized (n=35,199) and 1.05 (95%CI 0.99-1.11, , p-value, test for trend=0.04) for low/intermediate grade (n=34,366) PC. CONCLUSIONS: Weak nonsignificant associations were observed between total dietary fiber intake and risk of advanced forms of PC, high grade PC, and PC mortality. High dietary fiber intake from grains was associated with a modestly lower risk of advanced forms of PC and PC mortality.

Active and passive smoking and breast cancer in Japan: a pooled analysis of nine population-based cohort studies.

BACKGROUND: Epidemiological studies have shown inconsistent results regarding the link between smoking and breast cancer risk, despite the biological plausibility of a positive association. METHODS: Participants were 166 611 women from nine prospective cohort studies in Japan which launched in 1984-1994 and followed for 8-22 years. Information on smoking and secondhand smoke was obtained through self-administered baseline questionnaires. Breast cancer was defined as code C50 according to the International Classification of Diseases for Oncology, 3rd Edition or the International Classification of Diseases, 10th Revision. After adjusting for several potential confounders, relative risks for breast cancer were calculated in the individual studies according to the current or previous status of active and passive smoking using Cox regression, followed by a summary estimate of hazard ratios using random-effects meta-analyses. RESULTS: Of the 60 441 participants who reported being premenopausal and 106 170 who reported being postmenopausal at baseline, 897 and 1168 developed breast cancer during follow-up, respectively. Compared with never smokers, current smokers had a higher risk of developing breast cancer before the age of 50 years. In addition, ever smokers who started smoking at 30 years of age or younger, or who started smoking before first childbirth, had a higher risk of developing breast cancer before the age of 50 years. No association between adulthood or childhood exposure to secondhand smoke and breast cancer was observed. CONCLUSION: Smoking may increase the risk of premenopausal breast cancer, and smoking earlier in life might be especially harmful. The impact of secondhand smoke needs further investigation.

Association of female reproductive and hormonal factors with gallbladder cancer risk in Asia: A pooled analysis of the Asia Cohort Consortium.

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone-related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16-1.70 for 17 years and older vs. 13-14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50-4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08-2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort.

Body mass index and lung cancer risk: Pooled analysis of 10 prospective cohort studies in Japan.

Mounting evidence suggests that body mass index (BMI) is inversely associated with the risk of lung cancer. However, relatively few studies have explored this association in Asian people, who have a much lower prevalence of obesity than Caucasians. We pooled data from 10 prospective cohort studies involving 444,143 Japanese men and women to address the association between BMI and the risk of lung cancer. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in each cohort using the Cox proportional hazards model. A meta-analysis was undertaken by combining the results from each cohort. Heterogeneity across studies was evaluated using Cochran's Q and I2statistics. During 5,730,013 person-years of follow-up, 6454 incident lung cancer cases (4727 men and 1727 women) were identified. Baseline BMI was inversely associated with lung cancer risk in men and women combined. While leanness (BMI <18.5) was associated with a higher risk of lung cancer (HR 1.35; 95% CI, 1.16-1.57), overweight and obesity were associated with a lower risk, with HRs of 0.77 (95% CI, 0.71-0.84) and 0.69 (95% CI, 0.45-1.07), respectively. Every 5 kg/m2 increase in BMI was associated with a 21% lower risk of lung cancer (HR 0.79; 95% CI, 0.75-0.83; p < 0.0001). Our pooled analysis indicated that BMI is inversely associated with the risk of lung cancer in the Japanese population. This inverse association could be partly attributed to residual confounding by smoking, as it was more pronounced among male smokers.

Association between reproductive factors with lung cancer incidence and mortality: A pooled analysis of over 308,000 females in the Asia cohort consortium.

Previous studies have investigated the association between reproductive factors and lung cancer risk; however, findings have been inconsistent. In order to assess this association among Asian women, a total of 308,949 female participants from 11 prospective cohorts and four Asian countries (Japan, Korea, China, and Singapore) were included. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CIs). A total of 3,119 primary lung cancer cases and 2247 lung cancer deaths were identified with a mean follow-up of 16.4 years. Parous women had a lower risk of lung cancer incidence and mortality as compared with nulliparous women, with HRs of 0.82 (95% CI = 0.70-0.96) and 0.78 (95% CI = 0.65-0.94). The protective association of parity and lung cancer incidence was greater among ever-smokers (HR = 0.66, 95% CI = 0.49-0.87) than in never-smokers (HR = 0.90, 95% CI = 0.74-1.09) (P-interaction = 0.029). Compared with age at first delivery ≤20 years, older age at first delivery (21-25, ≥26 years) was associated with a lower risk of lung cancer incidence and mortality. Women who ever used hormone replacements had a higher likelihood of developing non-small cell lung cancer (HR = 1.31, 95% CI = 1.02-1.68), compared to those who never used hormone replacements. Future studies are needed to assess the underlying mechanisms, the relationships within these female reproductive factors, and the potential changes in smoking habits over time.

Long-term use of anti-cholesterol drugs and cancer risks in a Japanese population.

Several studies have investigated the association between the use of anti-cholesterol drugs and cancer risks, of which results have been inconsistent. This study included 67,768 participants from the Japan Public Health Center-based Prospective Study. The data on anti-cholesterol drug use was collected using three questionnaires of the survey conducted every five years. We divided the participants into three groups according to the duration of the anti-cholesterol drug use. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). During the 893,009 person-years of follow-up from the 10-year follow-up survey, 8,775 participants (5,387 men and 3,388 women) were newly diagnosed with cancers. The duration of anti-cholesterol drug use was significantly associated with a decreased risk of liver cancer (HR:0.26, 95% CI 0.11-0.64 in > 5 y group) and with an increased risk of pancreatic cancer (HR:1.59, 95% CI 1.03-2.47 in > 5 y group). Moreover, a different trend was observed between men and women in the association with the risk of lung cancer. This study suggested that long-term use of anti-cholesterol drugs may have associations with a decreased incidence of liver cancer and with an increased incidence of pancreatic cancers.

Association of glycaemic index and glycaemic load with type 2 diabetes, cardiovascular disease, cancer, and all-cause mortality: a meta-analysis of mega cohorts of more than 100 000 participants.

BACKGROUND: There is debate over whether the glycaemic index of foods relates to chronic disease. We aimed to assess the associations between glycaemic index (GI) and glycaemic load (GL) and type 2 diabetes, cardiovascular disease, diabetes-related cancers, and all-cause mortality. METHODS: We did a meta-analysis of large cohorts (≥100 000 participants) identified from the Richard Doll Consortium. We searched the Cochrane Library, MEDLINE, PubMed, Embase, Web of Science, and Scopus for cohorts that prospectively examined associations between GI or GL and chronic disease outcomes published from database inception to Aug 4, 2023. Full-article review and extraction of summary estimates data were conducted by three independent reviewers. Primary outcomes were incident type 2 diabetes, total cardiovascular disease (including mortality), diabetes-related cancers (ie, bladder, breast, colorectal, endometrial, hepatic, pancreatic, and non-Hodgkin lymphoma), and all-cause mortality. We assessed comparisons between the lowest and highest quantiles of GI and GL, adjusting for dietary factors, and pooling their most adjusted relative risk (RR) estimates using a fixed-effects model. We also assessed associations between diets high in fibre and whole grains and the four main outcomes. The study protocol is registered with PROSPERO, CRD42023394689. FINDINGS: From ten prospective large cohorts (six from the USA, one from Europe, two from Asia, and one international), we identified a total of 48 studies reporting associations between GI or GL and the outcomes of interest: 34 (71%) on various cancers, nine (19%) on cardiovascular disease, five (10%) on type 2 diabetes, and three (6%) on all-cause mortality. Consumption of high GI foods was associated with an increased incidence of type 2 diabetes (RR 1·27 [95% CI 1·21-1·34]; p<0·0001), total cardiovascular disease (1·15 [1·11-1·19]; p<0·0001), diabetes-related cancer (1·05 [1·02-1·08]; p=0·0010), and all-cause mortality (1·08 [1·05-1·12]; p<0·0001). Similar associations were seen between high GL and diabetes (RR 1·15 [95% CI 1·09-1·21]; p<0·0001) and total cardiovascular disease (1·15 [1·10-1·20]; p<0·0001). Associations between diets high in fibre and whole grains and the four main outcomes were similar to those for low GI diets. INTERPRETATION: Dietary recommendations to reduce GI and GL could have effects on health outcomes that are similar to outcomes of recommendations to increase intake of fibre and whole grain. FUNDING: Banting and Best and the Karuna Foundation.

Genetic architecture of alcohol consumption identified by a genotype-stratified GWAS and impact on esophageal cancer risk in Japanese people.

An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.

Differential patterns of reproductive and lifestyle risk factors for breast cancer according to birth cohorts among women in China, Japan and Korea.

BACKGROUND: The birth cohort effect has been suggested to influence the rate of breast cancer incidence and the trends of associated reproductive and lifestyle factors. We conducted a cohort study to determine whether a differential pattern of associations exists between certain factors and breast cancer risk based on birth cohorts. METHODS: This was a cohort study using pooled data from 12 cohort studies. We analysed associations between reproductive (menarche age, menopause age, parity and age at first delivery) and lifestyle (smoking and alcohol consumption) factors and breast cancer risk. We obtained hazard ratios (HRs) with 95% confidence intervals (CIs) using the Cox proportional hazard regression analysis on the 1920s, 1930s, 1940s and 1950s birth cohorts. RESULTS: Parity was found to lower the risk of breast cancer in the older but not in the younger birth cohort, whereas lifestyle factors showed associations with breast cancer risk only among the participants born in the 1950s. In the younger birth cohort group, the effect size was lower for parous women compared to the other cohort groups (HR [95% CI] 0.86 [0.66-1.13] compared to 0.60 [0.49-0.73], 0.46 [0.38-0.56] and 0.62 [0.51-0.77]). Meanwhile, a higher effect size was found for smoking (1.45 [1.14-1.84] compared to 1.25 [0.99-1.58], 1.06 [0.85-1.32] and 0.86 [0.69-1.08]) and alcohol consumption (1.22 [1.01-1.48] compared to 1.10 [0.90-1.33], 1.15 [0.96-1.38], and 1.07 [0.91-1.26]). CONCLUSION: We observed different associations of parity, smoking and alcohol consumption with breast cancer risk across various birth cohorts.

Adult Height and Risk of Colorectal Cancer: A Pooled Analysis of 10 Population-based Cohort Studies in Japan.

BACKGROUND: While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. METHODS: We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. RESULTS: We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07-1.40), 1.22 (95% CI, 1.09-1.36), and 1.27 (95% CI, 1.08-1.49), respectively, in men and 1.21 (95% CI, 1.09-1.35), 1.23 (95% CI, 1.08-1.40), and 1.35 (95% CI, 1.003-1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. CONCLUSION: This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Dietary Consumption of Antioxidant Vitamins in Relation to Prostate Cancer Risk in Japanese Men: The Japan Public Health Center-based Prospective Study.

BACKGROUND: Many epidemiological studies have investigated dietary intake of antioxidant vitamins in relation to prostate cancer risk in Western countries, but the results are inconsistent. However, few studies have reported this relationship in Asian countries. METHODS: We investigated the association between intake of vitamins, including lycopene, α-carotene, ß-carotene, vitamin C, vitamin E, with prostate cancer risk in the Japan Public Health Center-based Prospective (JPHC) study. 40,720 men without history of cancer finished the food frequency questionnaire (FFQ) and were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer risk were calculated according to the quintiles of energy-adjusted intake of vitamins using Cox models. RESULTS: After an average of 15.2 years (617,599 person-years in total) of follow-up, 1,386 cases of prostate cancer were identified, including 944 localized cases and 340 advanced cases. No associations were observed in consumption of antioxidant vitamins, including α-carotene, ß-carotene, vitamin C, and vitamin E, and prostate cancer risk. Although higher lycopene intake was associated with increased risk of prostate cancer (highest vs lowest quintile, HR 1.24; 95% CI, 1.04-1.47; P for trend = 0.01), there was a null association of lycopene intake with risk of prostate cancer detected by subjective symptoms (HR 1.12; 95% CI, 0.79-1.58; P for trend = 0.11). CONCLUSION: Our study suggested no association between antioxidant intake of vitamins and prostate cancer risk.

The effect of age on the relationship between body mass index and risks of incident stroke subtypes: The JPHC study.

OBJECTIVE: The associations between body mass index (BMI) and stroke subtypes, particularly intracerebral hemorrhage, have not been consistent. Such inconsistencies may be due to differences in the age at which BMI was obtained. We examined the possible age modifications in the association between BMI and stroke risk. MATERIALS AND METHODS: We followed 88,754 participants, aged 40-69 years at baseline (1990-1994), of the Japan Public Health Center-based prospective (JPHC) study for stroke incidence. BMI was obtained using self-reported body weight and height, which were categorized using the following cut-off points: 18.5, 21, 23, 25, 27.5, and 30 kg/m2. Time-dependent Cox proportional hazards models that updated BMI and covariates using 5- and 10-year questionnaire responses were used to estimate hazard ratios and 95 % confidence intervals. The analyses were stratified by age group (40-59 and ≥60 years) and the age of the individuals was updated. RESULTS: During the median follow-up period of 19 years, we documented 4,690 strokes, including 2,781 ischemic strokes and 1,358 intracerebral hemorrhages. After adjusting for sex, age, smoking, alcohol consumption, leisure-time physical activity, history of hypertension, dyslipidemia, and diabetes mellitus, we observed a positive linear association between BMI and ischemic stroke (linear trend, p < 0.001) in both age groups (interaction p>0.05). In contrast, a curvilinear association between BMI and intracerebral hemorrhage was observed in both the middle (curvilinear trend, p=0.017) and the older group (curvilinear trend, p=0.098) (interaction p>0.05). CONCLUSION: BMI and stroke associations did not vary significantly with age, although the association may differ according to subtype.

Obesity is associated with biliary tract cancer mortality and incidence: A pooled analysis of 21 cohort studies in the Asia Cohort Consortium.

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2 ); normal (18.5-22.9 kg/m2 ); overweight (23-24.9 kg/m2 ); and obese (25+ kg/m2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis.

Reproducibility and dietary correlates of plasma polyphenols in the JPHC-NEXT Protocol Area study.

BACKGROUND: In recent years, an increasing number of epidemiological studies have suggested a role of polyphenols in the prevention of chronic diseases. Prospective cohort studies have typically measured polyphenol concentrations in a single blood sample and the reproducibility of plasma polyphenol measurements is largely unknown. OBJECTIVE: We evaluated the reproducibility of 35 plasma polyphenols collected at an interval of 1-year. We also examined correlations of these polyphenols with food group intakes calculated from weighed food records (WFR) and food frequency questionnaire (FFQ). METHODS: The study included 227 middle-aged participants from the JPHC-NEXT Protocol Area in Japan. We measured 35 polyphenols in plasma collected at two points 1-year apart. Food group intakes were calculated from 12-day WFR and FFQ. For the reproducibility analysis, the intraclass correlation coefficient (ICC) of 35 polyphenol concentrations were examined between the two points. Pearson's partial correlations was used to assess the correlation between polyphenols and food groups. RESULTS: Moderate- to high ICCs were observed for tea-originated polyphenols such as gallic acid, quercetin, epigallocatechin, and kaempferol - and coffee-derived polyphenols, such as caffeic acid, and ferulic acid. For the dietary analyses, moderate correlations were observed for non-alcoholic beverages intake and epigallocatechin, epicatechin, catechin, and gallic acid. For green tea, higher correlations were observed with these polyphenols. CONCLUSION: Plasma concentrations of tea and coffee-related polyphenols, except for catechin, had good reproducibility over a 1-year period. The correlations between intake of non-alcoholic beverages, particularly green tea, and tea polyphenols, indicated moderate- to high correlations.

Relationships of Total and Domain-Specific Moderate-to-Vigorous Physical Activity with All-Cause and Disease-Specific Mortality.

PURPOSE: This study aimed to investigate the relationships of moderate-to-vigorous physical activity (MVPA) with all-cause and disease-specific mortality. We also investigated how the association between MVPA at leisure time (LT-MVPA) and health outcomes differs at different MVPA at work (WT-MVPA) levels. METHODS: The 81,601 community-dwelling Japanese persons age 50-79 yr who responded to a questionnaire in 2000-2003 were followed until 2018. Cox proportional hazard model was used to examine the association of total MVPA with risks of all-cause, cancer, heart disease, stroke, and respiratory disease mortality. Then, we compared the mortality risk according to the tertile of LT-MVPA, stratified by the tertile of WT-MVPA. RESULTS: During the 15.1 yr of average follow-up, 16,951 deaths were identified. Even total MVPA below the recommended volume (i.e., 0.1-1.49 MET·h·d -1 ) was associated with 11% to 24% reductions in all-cause (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.82-0.96) and heart disease mortality (HR, 0.76; 95% CI, 0.61-0.94), compared with no MVPA at all. The further reduced risks were seen in MVPA up to 10 MET·h·d -1 . The inverse association between LT-MVPA and mortality risks was more evident at lower WT-MVPA, which was also inversely associated with the risks. CONCLUSIONS: Health benefits were observed at low levels of MVPA and up to 10 MET·h·d -1 , although the fine threshold for excessive MVPA was not clear. LT-MVPA had distinct health benefits especially for persons with lower WT-MVPA.