Plasma Albumin, Bilirubin, and Uric Acid and the Subsequent Risk of Cancer: A Case-Cohort Study in the Japan Public Health Center-based Prospective Study.

Several epidemiological studies have investigated the circulating levels of albumin, bilirubin, and uric acid (UA) in relation to cancer risk; however, they have provided equivocal evidence. In this prospective case-cohort study, we aimed to explore the association of plasma albumin, bilirubin, and UA levels with cancer incidence. We measured the plasma levels of albumin, bilirubin, and UA and investigated their association with cancer incidence in 3,584 cases and 4,270 randomly selected participants with a median follow-up of 15.8 years. The adjusted hazard ratios (HR) and 95% confidence intervals (CI) of total cancer for the highest (Q4) versus lowest quartile (Q1) was 0.77 (95% CI: 0.67-0.90, P for trend: <0.001) for albumin. This association was attenuated after excluding liver cancer cases with lower plasma albumin levels. Plasma bilirubin levels were positively related to liver cancer but inversely to total cancer after excluding liver cancer with adjusted HR Q4 vs. Q1 of 0.86 (95% CI: 0.74-0.99, P for trend = 0.015). Plasma UA levels were not dose-responsively associated with total cancer risk. Higher plasma bilirubin levels were associated with a decreased risk of total cancer after excluding liver cancer, which is likely attributed to the antioxidant properties of bilirubin.

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.

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 depressive symptoms with incident fractures: the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT).

This 5-year longitudinal study investigated the relationship between depressive symptoms and fracture risk in a large Japanese cohort. Depressive symptoms were a significant risk factor for hip fractures in women. PURPOSE: A relationship between depressive symptoms and fractures has not been clearly demonstrated. We aimed to investigate the relationship between depressive symptoms and 5-year fracture risk in the Japan Public Health Center-based Prospective Study for the Next Generation. METHODS: From 2011 to 2016, 114,092 participants were enrolled, and a follow-up survey was conducted 5 years later. We analyzed 30,552 men and 38,063 women aged 40-74 years who had no past fractures at baseline. Presence of depressive symptoms was defined as a modified 11-item Center for Epidemiological Studies Depression Scale score of 8 or higher, a history of depression, or use of antidepressants. Subjects were asked to report vertebral, upper limb, and/or hip fractures, except for traffic or work accidents, that occurred during the follow-up period. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for fracture were analyzed via logistic regression analysis to evaluate the relationship between depressive symptoms and fracture. RESULTS: Women with depressive symptoms demonstrated a high AOR for hip fractures (AOR: 2.78, 95% CI: 1.30 - 5.92); this result was consistent in post menopause women. In men, this association was not found for any age group or any type of fracture. CONCLUSIONS: Depressive symptoms in women may increase the risk of hip fractures. Further studies are required to explore this relationship in more detail.

Sex difference in the association of dietary fiber intake with visceral fat volume in Japanese adults.

PURPOSE: Dietary fiber is a possible nutritional component which aids in the prevention of visceral fat accumulation. We examined the association between dietary fiber intake and visceral fat volume (VFV) by sex, and further analysed the association by major food sources of dietary fiber. METHODS: In this cross-sectional study, we measured VFV in 2779 Japanese (1564 men and 1215 women) aged 40-89 who underwent positron emission tomography/computed tomography for cancer screening between 2004 and 2005. Dietary fiber intake was calculated based on a validated semi-quantitative food frequency questionnaire. The association between dietary fiber intake and VFV was investigated using multivariate linear regression models after adjustment for potential confounders. RESULTS: Total, soluble, and insoluble fiber intakes were inversely associated with VFV in men (Q1: 3740 cm3, Q4: 3517 cm3, Ptrend: 0.0006 for total fiber), but not in women (Q1: 2207 cm3, Q4: 2193 cm3,Ptrend: 0.88 for total fiber). Statistically significant sex difference was observed (Pinteraction = 0.001 for total fiber). Subgroup analyses by major food sources revealed that dietary fiber intakes from beans, vegetables and fruits showed an inverse association with VFV in men, while cereal fiber intake showed a tendency toward a positive association in both sexes (Q1: 3520 cm3, Q4: 3671 cm3, Ptrend: 0.05 in men, Q1: 2147 cm3, Q4: 2227 cm3, Ptrend: 0.10 in women). CONCLUSION: We observed a sex-specific association between dietary fiber intake and VFV in Japanese adults. This study suggests that efforts against visceral fat accumulation should take account of the source of dietary fiber.

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.

GWAS meta-analysis of kidney function traits in Japanese populations.

BACKGROUND: Genetic epidemiological evidence for the kidney function traits in East Asian population including Japanese remain still relatively unclarified. Especially, the number of GWASs for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful. METHODS: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]). RESULTS: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; p < 5×10-8), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; p < 5×10-8), of which one locus (more than 1Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. CONCLUSIONS: The present GWAS meta-analysis of largest genome cohort studies in Japanese provided some original genomic loci associated with kidney function in Japanese, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

Development and preliminary validation of a prediction formula of sodium and sodium-to-potassium ratio based on multiple regression using 24-h urines.

Accurate measurement of sodium intake in the diet is challenging, and epidemiological studies can be hampered by the attenuation of associations due to measurement error in sodium intake. A prediction formula for habitual 24-h urine sodium excretion and sodium-to-potassium ratio might lead to more reliable conclusions. Five 24-h urinary samples and two Food Frequency Questionnaires (FFQs) were conducted among 244 Japanese participants aged 35-80 years. We conducted multivariate linear regression analysis with urinary excretion as dependent variables and eating behaviour and food frequency as independent variables. Empirical weights of sodium excretion and sodium-to-potassium ratio were extracted. Preliminary validity was also assessed by randomly dividing the subjects into development and validation groups based on the correlation coefficient between estimates by the prediction formula and urinary excretion. Taste preference, soy sauce use at the table, frequency of pickled vegetables intake and number of bowls of miso soup were extracted as determinants of sodium excretion. Correlation coefficients between the estimates and urinary excretion for men and women were 0.42 and 0.43, respectively, for sodium and 0.49 and 0.50, respectively, for sodium-to-potassium ratio. This prediction formula may provide more accurate estimation of sodium intake and sodium-to-potassium ratio than the food composition approach.

Relation between a history of glaucoma and subjective happiness: the JPHC-Next study.

OBJECTIVE: This population-based, cross-sectional study was performed to investigate the relationship between a history of glaucoma and subjective happiness. METHODS AND ANALYSIS: We conducted a cross-sectional questionnaire-based survey of 92 397 Japanese men and women aged 40-74 who participated in the Japan Public Health Center-based Prospective Study for the Next Generation study. A multivariable logistic regression model was used to estimate the ORs of glaucoma associated with subjective happiness and their two-sided 95% CIs. RESULTS: Among 40 727 men and 51 670 women, 1733 participants (635 men, 1098 women) had a history of glaucoma. The odds of unhappiness in male participants with a history of glaucoma were higher (OR 1.26; 95% CI 1.05 to 1.51) than in female participants (OR 1.05; 95% CI 0.90 to 1.23). In a subgroup analysis stratified by age, among participants with a history of glaucoma, males in the younger group (40-59 years) showed the most robust association with unhappiness (OR 1.40; 95% CI 1.04 to 1.88). CONCLUSIONS: These findings suggest that a history of glaucoma is related with subjective unhappiness, especially in men.

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.

Urinary Biomarkers in Screening for the Usual Intake of Fruit and Vegetables, and Sodium, Potassium, and the Sodium-to-Potassium Ratio: Required Number and Accuracy of Measurements.

Because of within-individual variation, surveys to estimate an individual's usual food intake must be conducted over many days, in general. Here, using non-invasive biomarkers, we examined the number of measurements required to screen for the usual intake of fruit and vegetables, in addition to sodium, potassium, and the sodium-to-potassium (Na/K) ratio. Participants were 202 subjects aged 40-74 years from five areas of Japan who completed weighed food records (WFR) and five 24-hour urinary collections (24-h UCs) between 2012 and 2013. The number of 24-h UCs required to screen for intake that deviated from guidelines estimated by the WFR and their accuracies were assessed by the area under the curve (AUC) in a receiver-operating characteristics (ROC) analysis. The single urinary excretion of sodium, potassium, and the Na/K ratio showed moderate performance (AUC value: >0.7) in discriminating deviations from their criteria by respective intake based on the WFR. Urinary potassium excretion also showed moderate performance (AUC value: >0.7) in estimating the intake of vegetables but could not be used to estimate fruit intake even after five collections. The non-invasive measurement of biomarkers in a single 24-h UC showed moderate performance in screening the usual intake of vegetables, as measured based on the 12-day WFR, as well as of sodium, potassium, and the Na/K ratio.

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.

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.

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.

Association between birth weight and prevalence of cardiovascular disease and other lifestyle-related diseases among Japanese population: JPHC-NEXT Study.

BACKGROUND: An association between birth weight and cardiovascular disease (CVD) in adulthood has been observed in many countries; however, only a few studies have been conducted in Asian populations. METHODS: We used data from the baseline survey (2011-2016) of the Japan Public Health Center-based Prospective Study for the Next Generation Cohort, which included 114,105 participants aged 40-74 years. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were calculated from the prevalence of present and past histories of CVD and other lifestyle-related diseases, including hypertension, diabetes, hyperlipidemia, and gout, by birth weight, using Poisson regression. RESULTS: The prevalence of CVD increased with lower birth weight, with the highest prevalence among those with birth weight under 1,500 grams (males 4.6%; females 1.7%) and the lowest one among those with birth weight at or over 4,000g (males 3.7%: females 0.8%). Among 88.653 participants (41,156 males and 47,497 females) with complete data on possible confounders, birth weight under 1,500g was associated with a higher prevalence of CVD (aPR 1.76 [95%CI 1.37-2.26]), hypertension (aPR 1.29 [95%CI 1.17-1.42]), and diabetes (aPR 1.53 [95%CI 1.26-1.86]) when a birth weight of 3,000-3,999 grams was used as the reference. Weaker associations were observed for birth weight of 1500-2499 grams and 2500-2999 grams, while no significant associations were observed for birth weight at or over 4000 g. The association between birth weight and the prevalence of hyperlipidemia was less profound, and no significant association was observed between birth weight and gout. CONCLUSION: Lower birth weight was associated with a higher prevalence of CVD, hypertension, and diabetes in the Japanese population.

Reproductive Factors in the Risk of Bladder Cancer and Upper Urinary Tract Cancer: The Japan Public Health Center-Based Prospective Study.

BACKGROUND: Reproductive factors are hypothesized to play a role in the incidence of bladder cancer and upper urinary tract cancer (UUTC, together, urothelial cancer). However, evidence regarding these associations is limited, particularly in Asian populations. METHODS: We analyzed data from 55,882 females ages 40 to 69 years, and performed Cox proportional hazards regression analyses with three types of adjustment, namely age; reproductive factor of interest and covariates in addition to age (conventional model); and other reproductive factors in addition to the multivariable adjusted model (reproductive model). RESULTS: During an average of 20.2 years of follow-up, 194 urothelial cancer cases (145 bladder cancer cases and 49 UUTC cases) were identified. Early age at natural menopause (<44 years, compared with 49-51 years) increased bladder cancer risk in the reproductive model (HR, 2.09; 95% CI, 1.04-4.20). An association between urothelial cancer/bladder cancer and age at menopause, including both natural and surgical/induced, was significant in the reproductive model (HR, 1.74; 95% CI, 1.09-2.77; and HR, 1.94; 95% CI, 1.15-3.28, respectively). Early age at natural menopause was suggested to increase urothelial cancer risk in the reproductive model (HR, 1.78; 95% CI, 0.93-3.42). CONCLUSIONS: Our findings suggest a significant association between age at menopause and incidence of urothelial cancer/bladder cancer among Asian populations. This study aids understanding the role of reproductive factors in urothelial cancer/bladder cancer incidence. IMPACT: In Japanese populations, age at menopause is suggested to be associated with urothelial cancer/bladder cancer incidence, especially regarding early natural menopause.

Dietary Fish and n-3 Polyunsaturated Fatty Acid Consumption, and Renal Cell Carcinoma Risk in Japan: The Japan Public Health Center-Based Prospective Study.

BACKGROUND: Previous epidemiologic studies found inconsistent associations between fish consumption and renal cell carcinoma (RCC). Although the consumption of n-3 polyunsaturated fatty acids (PUFA) was reported to protect against the development of some types of cancer, little is known regarding its association with RCC. METHODS: We investigated the association between fish and n-3 PUFA consumption and RCC risk using the Japan Public Health Center-based Prospective Study. We examined data from 84,063 eligible Japanese participants aged 45 to 74 years who responded to a validated food frequency questionnaire for Cohort I in 1995 and Cohort II in 1998. The participants were followed-up until 2013. HRs and 95% confidence intervals (CI) were estimated using a multivariable-adjusted Cox proportional hazard model, and the exposure level was categorized into quartiles. RESULTS: Among the 1,272,298 person-years of follow-up, 262 cases of newly diagnosed RCC were identified. The multivariate-adjusted HRs for the highest vs. lowest quartile of fish, including shellfish, were (HR = 1.43; 95% CI, 0.98-2.07) and the individual marine n-3 PUFAs were (HR = 1.56; 95% CI, 1.07-2.28; Ptrend = 0.09) for eicosapentenoic acid, (HR = 1.81; 95% CI, 1.27-2.59; Ptrend = 0.01) for docosapentaenoic acid, and (HR = 1.56; 95% CI, 1.07-2.27; Ptrend = 0.09) for docosahexaenoic acid. RCC were further categorized on the basis of diagnosis methods and cancer stage, and the positive correlation did not change substantially. CONCLUSIONS: We demonstrated that high consumption of n-3 PUFA is associated with RCC risk. IMPACT: The positive association between n-3 PUFA and RCC risk was observed in Japanese who consume higher amounts of fish than Western populations.

Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review.

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.

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.

BACKGROUND: High 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. METHODS: A 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. RESULTS: No 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). CONCLUSIONS: None 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.