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Background: Parkinson's disease (PD) is a complex neurodegenerative disease with an elusive etiology that involves the interaction between genetic, behavioral, and environmental factors. Recently, epigenetic modifications, particularly DNA methylation, have been recognized to play an important role in the onset of PD. Glycoprotein non-metastatic melanoma protein B (GPNMB), a type I transmembrane protein crucial for immune cell activation and maturation, has emerged as a potential biomarker for the risk of PD. This research aims to investigate the influence of exercise and gender on the regulation of methylation levels of GPNMB cg17274742 in individuals. Methods: We analyze data from 2,474 participants in the Taiwan Biobank, collected from 2008 and 2016. Methylation levels at the GPNMB cg17274742 CpG site were measured using Illumina Infinium MethylationEPIC beads. After excluding individuals with incomplete data or missing information on possible risk factors, our final analysis included 1,442 participants. We used multiple linear regression models to assess the association between sex and exercise with adjusted levels of GPNMB cg17274742 for age, BMI, smoking, drinking, coffee consumption, serum uric acid levels, and hypertension. Results: Our results demonstrated that exercise significantly influenced the methylation levels of GPNMB cg17274742 in males (β = -0.00242; p = 0.0026), but not in females (β = -0.00002362; p = 0.9785). Furthermore, male participants who exercised showed significantly lower levels of methylation compared to the reference groups of the female and non-exercising reference groups (β = -0.00357; p = 0.0079). The effect of the interaction between gender and exercise on the methylation of GPNMB cg17274742 was statistically significant (p = 0.0078). Conclusion: This study suggests that gender and exercise can modulate GPNMB cg17274742, with hypomethylation observed in exercise men. More research is needed to understand the underlying mechanisms and implications of these epigenetic changes in the context of risk and prevention strategies. [ABSTRACT FROM AUTHOR]

Background To identify the prevalence of sleep disorders in China through a large sample study. To explore the relevant social determinants affecting residents' sleep status at both individual and provincial levels based on the theoretical framework of the Dahlgren-Whitehead model. Methods A nationwide cross-sectional web-based survey was conducted from January 20 to February 28, 2019 across 31 provinces of China. The Pittsburgh Sleep Quality Index was used to evaluate residents' sleep quality. Multilevel linear regression analysis was used to analyse the influencing factors of sleep disorder. Results A sample of 107 650 residents completed the survey, and 94 454 questionnaires were included in the final analysis. The crude incidence rate and the age-adjusted rate of sleep disorder in Chinese residents were 19.16% and 21.25%, respectively. Those who were older, female, smokers, drinkers, married, divorced, or widowed, retired, more educated (regression coefficient (b) = 0.172, P < 0.05), had worse self-perceived economic status, and lived far away from community health services (b = 0.758, P < 0.05) were more likely to have sleep problems. Physical exercise, social support (b = -1.705, P < 0.05), and greening coverage of residential areas (b = -1.769, P < 0.05) were protective factors for residents' sleep quality. Conclusions Sleep disorders are prevalent in the Chinese population, with varying incidence rates across provinces. To improve sleep quality, the Chinese government and health management departments should pay more attention to vulnerable groups and promote healthy lifestyles through education. Additionally, the social network can be utilized to provide social support. Improving the ecological environment and daily living environment is also essential. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is a major public health problem globally and it is a leading cause of death and disability in developing countries. This review aims to estimate the pooled prevalence of hypertension and its determinants in Ethiopia. Methods: A systematic literature search was conducted at the electronic databases (PubMed, Hinari, and Google Scholar) to locate potential studies. Heterogeneity between studies checked using Cochrane Q test statistics and I2 test statistics and small study effect were checked using Egger's statistical test at 5% significance level. Sensitivity analysis was checked. A random-effects model was employed to estimate the pooled prevalence of hypertension and its determinants in Ethiopia. Results: In this review, 38 studies that are conducted in Ethiopia and fulfilled the inclusion criteria with a total number of 51,427 study participants were reviewed. The overall pooled prevalence of hypertension in the country was 21.81% (95% CI: 19.20–24.42, I2 = 98.35%). The result of the review also showed that the point of prevalence was higher among males (23.21%) than females (19.62%). When we see the pervasiveness of hypertension from provincial perspective; the highest prevalence of hypertension was observed in Addis Ababa (25.35%) and the lowest was in Tigray region (15.36%). In meta-regression analysis as the mean age increases by one year, the likelihood of developing hypertension increases by a factor of 0.58 times (β = 0.58, 95% CI: 0.31–0.86, R2 = 36.67). Male sex (OR = 1.29, 95% CI: 1.03–1.61, I2 = 81.35%), age > 35 years (OR = 3.59, 95% CI: 2.57–5.02, I2 = 93.48%), overweight and/or obese (OR = 3.34, 95% CI: 2.12–5.26, I2 = 95.41%), khat chewing (OR = 1.42, 95% CI: I2 = 62%), alcohol consumption (OR = 1.50, 95% CI: 1.21–1.85, I2 = 64%), family history of hypertension (OR = 2.56, 95% CI: 1.64–3.99, I2 = 83.28%), and family history of diabetes mellitus (OR = 3.69, 95% CI: 1.85–7.59, I2 = 89.9%) are significantly associated with hypertension. Conclusion: Hypertension is becoming a major public health problem in Ethiopia. Nearly two out of ten individuals who are older than 18 years living with hypertension. Sex, age, overweight and/or obese, khat chewing, alcohol consumption, and family history of hypertension and diabetes mellitus are statistically significant determinant factors for hypertension in Ethiopia. Primary attention should be given for behavioral risk factors to tackle the alarming increase of hypertension in Ethiopia. [ABSTRACT FROM AUTHOR]

We examined the proportions of multiple types of breast cancers in the population that were attributable to established risk factors, focusing on behaviors that are modifiable at menopause. We estimated the full and partial population attributable risk percentages (PAR%) by combining the relative risks and the observed prevalence rates of the risk factors of interest. A total of 8,421 cases of invasive breast cancer developed in postmenopausal women (n = 121,700) in the Nurses' Health Study from 1980-2010. We included the following modifiable risk factors in our analyses: weight change since age 18 years, alcohol consumption, physical activity level, breastfeeding, and menopausal hormone therapy use. Additionally, the following nonmodifiable factors were included: age, age at menarche, height, a combination of parity and age at first birth, body mass index at age 18 years, family history of breast cancer, and prior benign breast disease. When we considered all risk factors (and controlled for age), the PAR% for invasive breast cancers was 70.0% (95% confidence interval: 55.0, 80.7). When considering only modifiable factors, we found that changing the risk factor profile to the lowest weight gain, no alcohol consumption, high physical activity level, breastfeeding, and no menopausal hormone therapy use was associated with a PAR% of 34.6% (95% confidence interval: 22.7, 45.4). The PAR% for modifiable factors was higher for estrogen receptor-positive breast cancers (PAR% = 39.7%) than for estrogen receptor-negative breast cancers (PAR% = 27.9%). Risk factors that are modifiable at menopause account for more than one-third of postmenopausal breast cancers; therefore, a substantial proportion of breast cancer in the United States is preventable. [ABSTRACT FROM AUTHOR]

Background: These trials are the first randomised controlled trials of telephone-based weight management and healthy lifestyle interventions for low back pain and knee osteoarthritis. This article describes the protocol and statistical analysis plan. Method: These trials are parallel randomised controlled trials that investigate and compare the effect of a telephone-based weight management and healthy lifestyle intervention for improving pain intensity in overweight or obese patients with low back pain or knee osteoarthritis. The analysis plan was finalised prior to initiation of analyses. All data collected as part of the trial were reviewed, without stratification by group, and classified by baseline characteristics, process of care and trial outcomes. Trial outcomes were classified as primary and secondary outcomes. Appropriate descriptive statistics and statistical testing of between-group differences, where relevant, have been planned and described. Conclusions: A protocol for standard analyses was developed for the results of two randomised controlled trials. This protocol describes the data, and the pre-determined statistical tests of relevant outcome measures. The plan demonstrates transparent and verifiable use of the data collected. This a priori protocol will be followed to ensure rigorous standards of data analysis are strictly adhered to. [ABSTRACT FROM AUTHOR]

Background: Studies on the association between alcohol consumption and colorectal cancer (CRC) prognosis have yielded inconsistent results. Objective: The associations of lifetime and 1-y prediagnostic alcohol consumption with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. Design: In 2003-2010, 3121 patients diagnosed with CRC were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.8 y. With the use of Cox proportional hazard regression, associations between lifetime and recent alcohol consumption and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed. Results: In this patient cohort with a median age of 69 y at diagnosis, lifetime abstainers showed poorer overall [adjusted HR (aHR): 1.25; 95% CI: 1.03, 1.52] and CRC-specific (aHR: 1.37; 95% CI: 1.10, 1.70) survival than lifetime light drinkers (women: >0-12 g/d; men: >0-24 g/d). Lifetime heavy drinkers showed poorer overall (aHR: 1.37; 95% CI: 1.06, 1.78) and disease-free (aHR: 1.38; 95% CI: 1.09, 1.74) survival. Alcohol abstaining in the year before diagnosis was associated with poorer overall (aHR: 1.42; 95% CI: 1.20, 1.68), CRC-specific (aHR: 1.38; 95% CI: 1.13, 1.68), and disease-free (aHR: 1.23; 95% CI: 1.05, 1.44) survival. Lifetime abstainers with nonmetastatic disease showed poorer CRC-specific (aHR: 1.48; 95% CI: 1.10, 2.00) and recurrence-free (aHR: 1.32; 95% CI: 1.02, 1.70) survival. Wine abstaining but not beer or liquor abstaining was associated with poorer survival. Associations between alcohol consumption and prognosis varied according to presence of diabetes and age. Conclusions: Prediagnostic alcohol abstaining and heavy drinking were associated with poorer survival after a CRC diagnosis than light drinking. The protective effects of light consumption might be restricted to wine, and associations might differ according to age and presence of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Lipid biomarkers, such as HDL-cholesterol concentrations, have been shown to have positive, inverse, and null associations with total, breast, and colorectal cancer risks. Studies of novel lipid biomarkers, such as apolipoprotein A-I (apo A-I) and apolipoprotein B- 100 (apo B-100), and cancer risk have been sparse, to our knowledge. Objectives: We evaluated the prospective association of total, breast, colorectal, and lung cancers and cancer mortality with circulating lipid biomarkers in 15,602 female health professionals in the Women's Health Study (aged ≥45 y, free of cardiovascular disease and cancer, and without hormone replacement therapy or lipid-lowering medications at baseline). Design: Cox regression models estimated HRs of cancer endpoints (19 y median follow-up) across quartiles 1 (reference) to 4 of each lipid biomarker after adjustment for cancer risk factors. Results: Confirmed cases included 2163 incident cancer cases (864 breast, 198 colorectal, and 190 lung cancers) and 647 cancer deaths. Total cancer risk was significantly lower in the highest quartile of apo A-I (adjusted HR: 0.79; 95% CI: 0.70, 0.90; P-trend = 0.0008) and HDL cholesterol (HR: 0.85; 95% CI: 0.75, 0.97; P-trend = 0.01). For site-specific cancers, significant associations included colorectal cancer risk with HDL cholesterol (HR: 0.63; 95% CI; 0.41, 0.98; P-trend = 0.03), triglycerides (HR: 1.86; 95% CI: 1.17, 2.97; P-trend = 0.02), and apo B-100 (HR: 1.60; 95% CI: 1.03, 2.49; P-trend = 0.006) and lung cancer risk with HDL cholesterol (HR: 0.59; 95% CI: 0.38, 0.93; P-trend = 0.01). LDL cholesterol was not significantly associated with risk of total cancer or any site-specific cancers. In time-dependent models that were adjusted for the use of a lipid-lowering medication after baseline, these associations remained. Conclusions: Lipids were associated with total, lung, and colorectal cancer risks in women. Lifestyle interventions for heart-disease prevention, which reduce apo B-100 or raise HDL cholesterol, may be associated with reduced cancer risk. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479. [ABSTRACT FROM AUTHOR]

Background: The role of n–6 (ω-6) polyunsaturated fatty acids (PUFAs) in type 2 diabetes (T2D) is inconclusive. In addition, little is known about how factors involved in PUFA metabolism, such as zinc, may affect the associations. Objectives: We investigated the associations of serum n–6 PUFAs and activities of enzymes involved in PUFA metabolism, Δ5 desaturase (D5D) and Δ6 desaturase (D6D), with T2D risk to determine whether serum zinc concentrations could modify these associations. Design: The study included 2189 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 y and free of T2D at baseline in 1984–1989. T2D was assessed by selfadministered questionnaires, by fasting and 2-h oral-glucose-tolerance test blood glucose measurement at re-examination rounds 4, 11, and 20 y after baseline, and by record linkage to the hospital discharge registry and the reimbursement register on diabetes medication expenses. Multivariate-adjusted Cox proportional hazards regression models were used to analyze associations. Results: During the average follow-up of 19.3 y, 417 men developed T2D. Those with higher estimated D5D activity (extreme-quartile HR: 0.55; 95% CI: 0.41, 0.74; P-trend , 0.001) and higher concentrations of total n–6 PUFAs (HR: 0.54; 95% CI: 0.41, 0.73; P-trend , 0.001), linoleic acid (LA; HR: 0.52; 95% CI: 0.39, 0.70; P-trend , 0.001), and arachidonic acid (AA; HR: 0.62; 95% CI: 0.46, 0.85; P-trend = 0.007) had a lower risk and those with higher concentrations of g-linolenic acid (GLA; HR: 1.28; 95% CI: 0.98, 1.68; P = 0.021) and dihomog- linolenic acid (DGLA; HR: 1.38; 95% CI: 1.04, 1.84; P-trend = 0.005) and higher D6D activity had a higher (HR: 1.50; 95% CI: 1.14, 1.97; P-trend , 0.001) multivariate-adjusted risk of T2D. Zinc mainly modified the association with GLA on T2D risk, with a higher risk observed among those with serum zinc concentrations above the median (P-interaction = 0.04). Conclusions: Higher serum total n–6 PUFA, LA, and AA concentrations and estimated D5D activity were associated with a lower risk of incident T2D, and higher GLA and DGLA concentrations and estimated D6D activity were associated with a higher risk. In addition, a higher serum zinc concentration modified the association of GLA on the risk of T2D. [ABSTRACT FROM AUTHOR]

Background: Observational studies on dietary potassium and risk of cardiovascular disease (CVD) have reported weak-to-modest inverse associations. Long-term prospective studies with multiple 24-h urinary samples for accurate estimation of habitual potassium intake, however, are scarce. Objective: We examined the association between urinary potassium excretion and risk of blood pressure–related cardiovascular outcomes. Design: We studied 7795 subjects free of cardiovascular events at baseline in the Prevention of Renal and Vascular End-stage Disease study, a prospective, observational cohort with oversampling of subjects with albuminuria at baseline. Main cardiovascular outcomes were CVD [including ischemic heart disease (IHD), stroke, and vascular interventions], IHD, stroke, and new-onset heart failure (HF). Potassium excretion was measured in two 24-h urine specimens at the start of the study (1997–1998) and midway through follow-up (2001–2003). Results: Baseline median urinary potassium excretion was 70 mmol/24 h (IQR: 56–84 mmol/24 h). During a median follow-up of 10.5 y (IQR: 9.9–10.8 y), a total of 641 CVD, 465 IHD, 172 stroke, and 265 HF events occurred. After adjustment for age and sex, inverse associations were observed between potassium excretion and risk [HR per each 26- mmol/24-h (1-g/d) increase; 95% CI] of CVD (0.87; 0.78, 0.97) and IHD (0.86; 0.75, 0.97), as well as nonsignificant inverse associations for risk of stroke (0.85; 0.68, 1.06) and HF (0.94; 0.80, 1.10). After further adjustment for body mass index, smoking, alcohol consumption, education, and urinary sodium and magnesium excretion, urinary potassium excretion was not statistically significantly associated with risk (multivariable- adjusted HR per 1-g/d increment; 95% CI) of CVD (0.96; 0.85, 1.09), IHD (0.90; 0.81, 1.04), stroke (1.09; 0.86, 1.39), or HF (0.99; 0.83, 1.18). No associations were observed between the sodium-to-potassium excretion ratio and risk of CVD, IHD, stroke, or HF. Conclusion: In this cohort with oversampling of subjects with albuminuria at baseline, urinary potassium excretion was not independently associated with a lower risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: In general populations, the effects of dietary cholesterol on blood cholesterol concentrations are modest. However, the relation is stronger in those with an ε4 allele in the apolipoprotein E gene (APOE). There is little information on the association between cholesterol intake and the risk of coronary artery disease (CAD) among those with the ApoE4 phenotype. Objective: We investigated the associations of intakes of cholesterol and eggs, a major source of dietary cholesterol, with carotid intima-media thickness and the risk of incident CAD in middle-aged and older men from eastern Finland. Design: The study included 1032 men aged 42-60 y in 1984-1989 at the baseline examinations of the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Data on common carotid artery intima-media thickness (CCA-IMT) were available for 846 men. Dietary intakes were assessed with 4-d food records. Associations with incident CAD and baseline CCA-IMT were analyzed by using Cox regression and ANCOVA, respectively. Results: The ApoE4 phenotype was found in 32.5% of the men. During the average follow-up of 20.8 y, 230 CAD events occurred. Egg or cholesterol intakes were not associated with the risk of CAD. Each 1 additional egg (55 g)/d was associated with a multivariable-adjusted HR of 1.17 (95% CI: 0.85, 1.61) in the ApoE4 noncarriers and an HR of 0.93 (95% CI: 0.50, 1.72) in the ApoE4 carriers (P-interaction = 0.34). Each 100-mg/d higher cholesterol intake was associated with an HR of 1.04 (95% CI: 0.89, 1.22) in the ApoE4 noncarriers and an HR of 0.95 (95% CI: 0.73, 1.25) in the ApoE4 carriers (P-interaction = 0.81). Egg or cholesterol intakes were also not associated with increased CCA-IMT. Conclusion: Egg or cholesterol intakes were not associated with increased CAD risk, even in ApoE4 carriers (i.e., in highly susceptible individuals). [ABSTRACT FROM AUTHOR]

Background: Previous cohort studies have shown that moderate alcohol consumption was associated with a lower risk of type 2 diabetes (T2D). However, whether these associations differ according to the characteristics of patients with T2D remains controversial. Objective: The purpose of this study was to explore and summarize the evidence on the strength of the association between alcohol consumption and the subsequent risk of T2D by using a dose-response meta-analytic approach. Design: We identified potential studies by searching the PubMed, Embase, and Cochrane Library databases up to 24 March 2015. Prospective observational studies that evaluated the relation between alcohol consumption and the risk of T2D and reported its effect estimates with 95% CIs were included. Results: Analyses were based on 706,716 individuals (275,711 men and 431,005 women) from 26 studies with 31,621 T2D cases. We detected a nonlinear relation between alcohol consumption and the risk of T2D, which was identified in all cohorts (P-trend < 0.001, P-nonlinearity < 0.001), in men (P-trend < 0.001, P-nonlinearity < 0.001), and in women (P-trend < 0.001, P-nonlinearity < 0.001). Compared with the minimal category of alcohol consumption, light (RR: 0.83; 95% CI: 0.73, 0.95; P = 0.005) and moderate (RR: 0.74; 95% CI: 0.67, 0.82; P < 0.001) alcohol consumption was associated with a lower risk of T2D. However, heavy alcohol consumption had little or no effect on subsequent T2D risk. Furthermore, the summary RR ratio (RRR; male to female) of the comparison between moderate alcohol consumption and the minimal alcohol categories for T2D was significantly higher, and the pooled RRR (current smoker to never smoker) of light alcohol consumption was significantly reduced. Conclusions: Light and moderate alcohol consumption was associated with a lower risk of T2D, whereas heavy alcohol consumption was not related to the risk of T2D. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation is a central mechanism involved in cardiovascular diseases, cancer, diabetes, and chronic respiratory diseases, 4 leading causes of mortality. Diet is a major source of pro- and anti-inflammatory bioactive compounds. The Dietary Inflammatory Index (DII) was designed to estimate the overall inflammatory potential of the diet. Objective: Our aim was to study the prospective association between the DII and mortality, as well as assess whether antioxidant supplementation could modulate this association. Design: The Supplémentation en Vitamines et Minéraux Anti-oxydants study was a randomized, double-blind, placebo-controlled trial in which participants received low-dose antioxidants or a placebo from 1994 to 2002. In this observational prospective analysis, 8089 participants (mean ± SD age at baseline: 49.0 ± 6.3 y) were followed between 1994 and 2007 (median: 12.4 y). The DII was calculated from repeated 24-h dietary records; higher scores correspond to more proinflammatory diets. A total of 207 deaths occurred during follow-up, including 123 due to cancer and 41 due to cardiovascular events. Multivariate Cox proportional hazards models were computed. Results: Sex-specific tertiles of the DII were positively associated with cardiovascular + cancer mortality (HR for tertile 3 compared with tertile 1 = 1.53; 95% CI: 1.01, 2.32; P-trend = 0.05) and specific cancer mortality (HR for tertile 3 compared with tertile 1 = 1.83; 95% CI: 1.12, 2.99; P-trend = 0.02). The corresponding P value was 0.07 for all-cause mortality. The DII was statistically significantly associated with increased all-cause mortality in the placebo group (HR for tertile 3 compared with tertile 1 = 2.10; 95% CI: 1.15, 3.84; P-trend = 0.02) but not in the antioxidant-supplemented group (P-trend = 0.8; P-interaction = 0.098). Conclusion: These results suggest that a proinflammatory diet is associated with increased all-cause and cancer mortality and antioxidants may counteract some of the proinflammatory effects of the diet. This trial was registered at clinicaltrials.gov as NCT00272428. [ABSTRACT FROM AUTHOR]

Background: The association between saturated fatty acid (SFA) intake and ischemic heart disease (IHD) risk is debated. Objective: We sought to investigate whether dietary SFAs were associated with IHD risk and whether associations depended on 1) the substituting macronutrient, 2) the carbon chain length of SFAs, and 3) the SFA food source. Design: Baseline (1993-1997) SFA intake was measured with a food-frequency questionnaire among 35,597 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort. IHD risks were estimated with multivariable Cox regression for the substitution of SFAs with other macronutrients and for higher intakes of total SFAs, individual SFAs, and SFAs from different food sources. Results: During 12 y of follow-up, 1807 IHD events occurred. Total SFA intake was associated with a lower IHD risk (HR per 5% of energy: 0.83; 95% CI: 0.74, 0.93). Substituting SFAs with animal protein, cis monounsaturated fatty acids, polyunsaturated fatty acids (PUFAs), or carbohydrates was significantly associated with higher IHD risks (HR per 5% of energy: 1.27-1.37). Slightly lower IHD risks were observed for higher intakes of the sum of butyric (4:0) through capric (10:0) acid (HRSD: 0.93; 95% CI: 0.89, 0.99), myristic acid (14:0) (HRSD: 0.90; 95% CI: 0.83, 0.97), the sum of pentadecylic (15:0) and margaric (17:0) acid (HRSD: 0.91: 95% CI: 0.83, 0.99), and for SFAs from dairy sources, including butter (HRSD: 0.94; 95% CI: 0.90, 0.99), cheese (HRSD: 0.91; 95% CI: 0.86, 0.97), and milk and milk products (HRSD: 0.92; 95% CI: 0.86, 0.97). Conclusions: In this Dutch population, higher SFA intake was not associated with higher IHD risks. The lower IHD risk observed did not depend on the substituting macronutrient but appeared to be driven mainly by the sums of butyric through capric acid, the sum of pentadecylic and margaric acid, myristic acid, and SFAs from dairy sources. Residual confounding by cholesterol-lowering therapy and trans fat or limited variation in SFA and PUFA intake may explain our findings. Analyses need to be repeated in populations with larger differences in SFA intake and different SFA food sources. [ABSTRACT FROM AUTHOR]

Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity. Objective: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer. Design: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER2) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for α-carotene, β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, retinol, α-tocopherol, γ-tocopherol, and vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided. Results: In quintile 5 compared with quintile 1, α-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and β-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER2 breast tumors. The other analytes were not statistically associated with ER2 breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER2 and ER+ tumors was statistically significant only for β-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER2/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution). Conclusion: Our results indicate that higher concentrations of plasma β-carotene and α-carotene are associated with lower breast cancer risk of ER2 tumors. [ABSTRACT FROM AUTHOR]

Background: Most previous prospective studies in Western countries found no association between consumption of fish and n-3 (v-3) polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), for which the main source is fish, and pancreatic cancer risk. However, prospective evidence is still lacking among populations who have a relatively higher fish consumption. Objective: We investigated the association between fish and n-3 PUFA consumption and pancreatic cancer risk in a population-based, prospective study in Japanese men and women. Design: The Japan Public Health Center-based Prospective Study (JPHC study) has enrolled 140,420 subjects. We analyzed data on 82,024 eligible participants aged 45-74 y without a history of cancer who responded to a validated food-frequency questionnaire that included 138 items in 1995 for cohort I and in 1998 for cohort II. Participants were followed through 2010. HRs and corresponding 95% CIs for the highest compared with lowest quartile were calculated by using multivariable-adjusted Cox proportional hazards regression models. Results: During 1,068,774 person-years of follow-up, 449 newly diagnosed pancreatic cancers were identified. After the exclusion of pancreatic cancer cases in the first 3 y of follow-up, we found an inverse association of marine n-3 PUFA (EPA+DPA+DHA) and DHA consumption with pancreatic cancer risk: compared with the lowest quartile, multivariate-adjusted HRs in the highest quartile were 0.70 (95% CI: 0.51, 0.95; P-trend = 0.07) and 0.69 (0.51, 0.94; P-trend = 0.03), respectively. Associations for total fish, n-3 PUFA, EPA, and DPA consumption were similar but were not significant. Conclusion: High n-3 PUFA, especially marine n-3 PUFAs, and DHA consumption was associated with a lower risk of pancreatic cancer in a population with a large variation in fish consumption, although the data apply to only a portion of the JPHC study subjects. [ABSTRACT FROM AUTHOR]

Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer--hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having ≥4 cups (600 mL) coffee/d compared with,2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and total bilirubin, which--in combination--attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury. [ABSTRACT FROM AUTHOR]

Background: Observational data have suggested that intakes of nutrients involved in one-carbon metabolism are inversely associated with risk of colorectal carcinoma and adenomas. In contrast, results from some preclinical studies and cardiovascular and chemoprevention trials have raised concerns that high folate intake may promote carcinogenesis by facilitating the progression of established neoplasia. Objective: We tested the hypothesis that higher total folate intake (including food folate and folic acid from fortified foods and supplements) or other one-carbon nutrient intakes might be associated with poorer survival after a diagnosis of colorectal cancer. Design: We used rectal and colon cancer cases within the following 2 US prospective cohort studies: the Nurses' Health Study and the Health Professionals Follow-Up Study. Biennial questionnaires were used to gather information on medical history and lifestyle factors, including smoking and alcohol consumption. B-vitamin and methionine intakes were derived from food-frequency questionnaires. Data on tumor molecular characteristics (including microsatellite instability, CpG island methylator phenotype, KRAS, BRAF, and PIK3CA mutations, and long interspersed nucleotide element 1 methylation level) were available for a subset of cases. We assessed colorectal cancer-specific mortality according to postdiagnostic intakes of one-carbon nutrients with the use of multivariable Cox proportional hazards regression models. Results: In 1550 stage I--III colorectal cancer cases with a median follow-up of 14.9 y, we documented 641 deaths including 176 colorectal cancer-specific deaths. No statistically significant associations were observed between postdiagnostic intakes of folate or other one-carbon nutrients and colorectal cancer-specific mortality (multivariate P-trend ≥ 0.21). In an exploratory molecular pathologic epidemiology survival analysis, there was no significant interaction between one-carbon nutrients or alcohol and any of the tumor molecular biomarkers examined. Conclusions: Higher postdiagnostic intakes of one-carbon nutrients are not associated with the prognosis in stage I--III colorectal cancer. Our findings do not support the hypothesis that higher folate intake after colorectal cancer diagnosis might increase risk of cancer-related death. [ABSTRACT FROM AUTHOR]

Background: Higher intake of certain vitamins may protect against cochlear damage from vascular compromise and oxidative stress, thereby reducing risk of acquired hearing loss, but data are limited. Objective: We prospectively examined the relation between carotenoids, vitamin A, vitamin C, vitamin E, and folate intake and risk of self-reported hearing loss in women. Design: This prospective cohort study followed 65,521 women in the Nurses' Health Study II from 1991 to 2009. Baseline and updated information obtained from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between nutrient intake and self-reported hearing loss. Results: After 1,084,598 person-years of follow-up, 12,789 cases of incident hearing loss were reported. After multivariable adjustment, we observed modest but statistically significant inverse associations between higher intake of β-carotene and β-cryptoxanthin and risk of hearing loss. In comparison with women in the lowest quintile of intake, the multivariable-adjusted RR of hearing loss among women in the highest quintile was 0.88 (95% CI: 0.81, 0.94; P-trend < 0.001) for β-carotene and 0.90 (95% CI: 0.84, 0.96; P-trend < 0.001) for β-cryptoxanthin. In comparison with women with folate intake 200-399 µg/d, very low folate intake (<200 µg/d) was associated with higher risk (RR: 1.19; 95% CI: 1.01, 1.41), and higher intake tended to be associated with lower risk (P-trend = 0.04). No significant associations were observed for intakes of other carotenoids or vitamin A. Higher vitamin C intake was associated with higher risk; in comparison with women with intake <75 mg/d, the RR among women with vitamin C intake ≥1000 mg/d (mainly supplemental) was 1.22 (95% CI: 1.06, 1.42; P-trend = 0.02). There was no significant trend between intake of vitamin E intake and risk. Conclusion: Higher intakes of β-carotene, β-cryptoxanthin, and folate, whether total or from diet, are associated with lower risk of hearing loss, whereas higher vitamin C intake is associated with higher risk. [ABSTRACT FROM AUTHOR]

Background: Experimental studies suggest protective effects of vitamin D on breast carcinogenesis, particularly on estrogen receptor- positive tumors. Epidemiologic data are less conclusive. Objective: Our objective was to investigate the association between postmenopausal breast cancer risk and current or past vitamin D supplementation overall and according to the use of menopausal hormone therapy (MHT). Design: Between 1995 and 2008, 2482 invasive breast cancer cases were diagnosed among 57,403 postmenopausal women from the E3N prospective cohort during 581,085 person-years. Vitamin D supplementation was assessed from biennially self-administered questionnaires sent in 1995, 2000, 2002, and 2005 and from medicoadministrative data on drug reimbursements since 2004. Multivariable HRs for primary invasive breast cancer and 95% CIs were estimated by using Cox models. Results: A decreased postmenopausal breast cancer risk was associated with current (HR: 0.82; 95% CI: 0.69, 0.97) but not past (HR: 1.10; 95% CI: 0.92, 1.31) vitamin D supplementation (P-homogeneity = 0.02). The association with current vitamin D supplementation differed according to MHT use: ever users (HR: 0.74; 95% CI: 0.60, 0.90) and never users (HR: 1.13; 95% CI: 0.89, 1.56); Phomogeneity = 0.02. Conclusions: In this observational study, current vitamin D supplementation, mostly taken daily and combined with calcium, was associated with a decreased postmenopausal breast cancer risk in MHT users. These findings should be confirmed before considering vitamin D supplementation to partly balance the MHT-associated increased breast cancer risk. [ABSTRACT FROM AUTHOR]

Background: An association between desaturase activity and risk of type 2 diabetes (T2D) has been found in epidemiologic studies, but little is known about potential mediators of this association. Objective: We aimed to investigate the potential role of diabetes-related biomarkers as mediators of the association between estimated Δ5 desaturase (D5D), D6 desaturase (D6D), and stearoyl-CoA desaturase (SCD) activity and T2D risk. Design: We analyzed a case-cohort study (subcohort: n = 1533; verified incident T2D cases: n = 400), nested within the European Prospective Investigation into Cancer and Nutrition-Potsdam Study involving 27,548 middle-aged participants. We evaluated the impact of adjustment for several T2D-related biomarkers reflecting liver fat accumulation [reflected by g-glutamyltransferase (GGT), alanine transaminase (ALT), fetuin-A, and the algorithm-based fatty liver index (FLI)], dyslipidemia (high-density lipoprotein cholesterol, triglycerides), inflammation [C-reactive protein (CRP)], and adipo-nectin on the association between D5D, D6D, and SCD activity, estimated with fatty acid product-to-precursor ratios derived from erythrocyte membrane proportions, and T2D risk. Results: Estimated D5D activity was inversely associated with T2D risk, whereas D6D and SCD activities were positively associated with risk of T2D [HRs (95% CIs) (highest vs. lowest tertile): 0.51 (0.36, 0.73), 1.68 (1.18, 2.39), and 1.82 (1.29, 2.58), respectively]. The association between estimated D5D, D6D, and SCD activities and risk of T2D was statistically significantly and markedly attenuated after adjustment for the FLI and, to a lesser extent, after adjustment for triglycerides, whereas adjustment for other desaturase-associated biomarkers (CRP, fetuin-A, ALT, and GGT) did not lead to appreciable attenuations. Conclusions: Liver fat accumulation, as reflected by the FLI, and dyslipidemia, as reflected by triglycerides, may partly explain the association between estimated D5D, D6D, and SCD activity and T2D risk. [ABSTRACT FROM AUTHOR]

Background: Evidence that alcohol consumption is inversely associated with long-term coronary artery disease (CAD) mortality independent of genetic and early life environmental factors is lacking. Objective: We evaluated whether alcohol consumption was prospectively associated with CAD mortality risk independent of familial factors. Design: In total, 843 male twins (396 pairs and 51 unpaired twins) aged 42-55 y (mean: 48 y) without baseline CAD reported beer, wine, and spirits consumption at baseline (1969-1973) and were followed up to 2010 in the prospective National Heart, Lung, and Blood Institute Twin Study. Data on usual alcohol consumption over the past year were collected. Outcome was time to event, where the primary event was death from CAD and secondary events were death from cardiovascular disease and all causes. HRs were estimated by using frailty survival models, both overall and within-pair. Results: There were 129 CAD deaths and 219 cardiovascular deaths during 41 y of follow-up. In the whole cohort, after adjustment for caloric intake and cardiovascular disease risk factors, overall HRs per 10-g increment in alcohol intake were 0.94 (95% CI: 0.89, 0.98) for CAD and 0.97 (95% CI: 0.93, 1.00) for cardiovascular mortality. The within-pair adjusted HRs for a twin with 10-g higher daily alcohol consumption than his co-twin were 0.90 (95% CI: 0.84, 0.97) for CAD and 0.95 (95% CI: 0.90, 1.00) for cardiovascular disease mortality in the cohort pooled by zygosity, which remained similar among monozygotic twins. All 3 beverage types tended to be associated with lower CAD mortality risk within-pair to a similar degree. Alcohol consumption was not associated with total mortality risk overall or within-pair. Conclusion: Higher usual alcohol consumption is associated with lower CAD mortality risk, independent of germline and early life environment and adulthood experience shared among twins, supporting a possible causal role of alcohol consumption in lowering CAD death risk. This trial was registered at clinicaltrials.gov as NCT00005124. [ABSTRACT FROM AUTHOR]

BACKGROUND: The prevalence of type 2 diabetes (T2D) is increasing around the world. Eggs are a major source of cholesterol, which has been associated with elevated blood glucose and an increased risk of T2D. However, there are limited and conflicting data from prospective population studies on the association between egg consumption and risk of T2D. OBJECTIVE: We investigated the association between egg consumption and risk of incident T2D in middle-aged and older men from eastern Finland. DESIGN: The study included 2332 men aged 42-60 y in 1984-1989 at the baseline examinations of the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study. Dietary intakes were assessed with 4-d food records at baseline. Incident T2D was assessed by self-administered questionnaires; by fasting and 2-h oral-glucose-tolerance-test blood glucose measurement at re-examination rounds 4, 11, and 20 y after baseline; and by record linkage to a hospital discharge registry and reimbursement register of diabetes medication expenses. Cox proportional hazards regression analyses were used to estimate associations with the risk of incident T2D. Associations with the metabolic risk markers at baseline and at the 4-y examinations were analyzed by ANCOVA. RESULTS: During an average follow-up of 19.3 y, 432 men developed T2D. After adjustment for potential confounders, those in the highest compared with the lowest egg intake quartile had a 38% (95% CI: 18%, 53%; P-trend across quartiles <0.001) lower risk of incident T2D. Analyses with metabolic risk markers also suggested an inverse association with fasting plasma glucose and serum C-reactive protein but not with serum insulin. The associations between cholesterol intake and risk of T2D, plasma glucose, serum insulin, and C-reactive protein were mainly nonsignificant, especially after accounting for egg consumption. CONCLUSION: Higher egg intake was associated with a lower risk of T2D in this cohort of middle-aged and older men. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dietary fats could affect glucose metabolism and obesity development and, thereby, may have a crucial role in the cause of type 2 diabetes (T2D). Studies indicated that replacing saturated with unsaturated fats might be favorable, and plant foods might be a better choice than animal foods. Nevertheless, epidemiologic studies suggested that dairy foods are protective. OBJECTIVE: We hypothesized that, by examining dietary fat and its food sources classified according to fat type and fat content, some clarification regarding the role of dietary fat in T2D incidence could be provided. DESIGN: A total of 26,930 individuals (61% women), aged 45-74 y, from the Malmö Diet and Cancer cohort were included in the study. Dietary data were collected by using a modified diet-history method. During 14 y of follow-up, 2860 incident T2D cases were identified. RESULTS: Total intake of high-fat dairy products (regular-fat alternatives) was inversely associated with incident T2D (HR for highest compared with lowest quintiles: 0.77; 95% CI: 0.68, 0.87; P-trend < 0.001). Most robust inverse associations were seen for intakes of cream and high-fat fermented milk (P-trend < 0.01) and for cheese in women (P-trend = 0.02). High intake of low-fat dairy products was associated with increased risk, but this association disappeared when low- and high-fat dairy were mutually adjusted (P-trend = 0.18). Intakes of both high-fat meat (P-trend = 0.04) and low-fat meat (P-trend < 0.001) were associated with increased risk. Finally, we did not observe significant association between total dietary fat content and T2D (P-trend = 0.24), but intakes of saturated fatty acids with 4-10 carbons, lauric acid (12:0), and myristic acid (14:0) were associated with decreased risk (P-trend < 0.01). CONCLUSIONS: Decreased T2D risk at high intake of high- but not of low-fat dairy products suggests that dairy fat partly could have contributed to previously observed protective associations between dairy intake and T2D. Meat intake was associated with increased risk independently of the fat content. [ABSTRACT FROM AUTHOR]

The colour of the edible portion of vegetables and fruit reflects the presence of specific micronutrients and phytochemicals. No existing studies have examined the relationship between the intake of vegetable and fruit colour groups and the risk of colorectal cancer. The present study, therefore, aimed to investigate these associations in a Chinese population. A case–control study was conducted between July 2010 and July 2014 in Guangzhou, China, in which 1057 consecutively recruited cases of colorectal cancer were frequency-matched to 1057 controls by age (5-year interval), sex and residence (rural/urban). A validated FFQ was used to collect dietary information during face-to-face interviews. Vegetables and fruit were classified into four groups according to the colour of their primarily edible parts: green; orange/yellow; red/purple; white. Unconditional logistic regression models were used to estimate the OR and 95 % CI. A higher consumption of orange/yellow, red/purple and white vegetables and fruit was inversely associated with the risk of colorectal cancer, with adjusted OR of 0·16 (95 % CI 0·12, 0·22) for orange/yellow, 0·23 (95 % CI 0·17, 0·31) for red/purple and 0·53 (95 % CI 0·40, 0·70) for white vegetables and fruit when the highest and lowest quartiles were compared. Total vegetable intake and total fruit intake have also been found to be inversely associated with colorectal cancer risk. However, the intake of green vegetable and fruit was not associated with colorectal cancer risk. The results of the present study, therefore, suggest that a greater intake of orange/yellow, red/purple and white vegetables and fruit is inversely associated with the risk of colorectal cancer. [ABSTRACT FROM PUBLISHER]

A number of studies have examined dietary patterns in various populations. However, to study to what extent such patterns capture meaningful differences in consumption of foods is of interest. In the present study, we identified important dietary patterns in Norwegian postmenopausal women (age 50–69 years, n 361), and evaluated these patterns by examining their associations with plasma carotenoids. Diet was assessed by a 253-item FFQ. These 253 food items were categorised into forty-six food groups, and dietary patterns were identified using principal component analysis. We used the partial correlation coefficient (radj) and multiple linear regression analysis to examine the associations between the dietary patterns and the plasma carotenoids α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene and zeaxanthin. Overall, four dietary patterns were identified: the ‘Western’; ‘Vegetarian’; ‘Continental’; ‘High-protein’. The ‘Western’ dietary pattern scores were significantly inversely correlated with plasma lutein, zeaxanthin, lycopene and total carotenoids ( − 0·25 ≤ radj≤ − 0·13). The ‘Vegetarian’ dietary pattern scores were significantly positively correlated with all the plasma carotenoids (0·15 ≤ radj≤ 0·24). The ‘Continental’ dietary pattern scores were significantly inversely correlated with plasma lutein and α-carotene (radj= − 0·13). No significant association between the ‘High-protein’ dietary pattern scores and the plasma carotenoids was found. In conclusion, the healthy dietary pattern, the ‘Vegetarian’ pattern, is associated with a more favourable profile of the plasma carotenoids than our unhealthy dietary patterns, the ‘Western’ and ‘Continental’ patterns. [ABSTRACT FROM PUBLISHER]

Background: Previous studies reported beneficial effects of cocoa or chocolate on insulin resistance, oxidative stress, and inflammation, which are important risk factors of type 2 diabetes mellitus (DM). However, it is unclear whether chocolate consumption is associated with risk of DM. Objective: We tested the hypothesis that chocolate consumption is inversely associated with incident DM in the Physicians' Health Study (PHS). Design: We prospectively analyzed data on 18,235 PHS participants who were free of DM at baseline (1997-2001). Chocolate consumption was obtained from a baseline food-frequency questionnaire. Incident DM was ascertained via annual follow-up questionnaires and validated in a subsample by a review of medical records. We used Cox proportional hazards models to estimate HRs and 95% CIs of DM. Results: The mean (±SD) age at baseline was 66.3 ± 9.2 y. During a mean follow up of 9.2 y, 1123 men (6.2%) developed DM. For self-reported chocolate consumption of none, 1-3 servings/mo, 1 serving/wk, and ≥2 servings/wk, multivariable-adjusted HRs (95% CIs) of DM adjusted for lifestyle, clinical, and dietary risk factors including total energy intake were 1.00 (referent), 0.93 (0.79, 1.09), 0.86 (0.72, 1.04), and 0.83 (0.69, 0.99), respectively (P-trend = 0.047). In secondary analyses, the inverse association of chocolate consumption and risk of DM was slightly stronger in subjects without a history of cardiovascular disease or heart failure (P-trend = 0.023). In addition, both age and BMI modified the chocolate-DM relation (P < 0.05 each). Conclusion: Our data support an inverse relation of chocolate intake with incident DM, which appears only to apply in younger and normal-body weight men after controlling for comprehensive life styles including total energy consumption. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that nut consumption is associated with beneficial cardiovascular outcomes. However, limited data are available on the association between nut intake and all-cause mortality. Objective: Our aim was to test the hypothesis that nut consumption is inversely associated with the risk of all-cause mortality. Design: In this prospective cohort study in 20,742 male physicians, we assessed nut intake between 1999 and 2002 via a food-frequency questionnaire and ascertained deaths through an endpoint committee. We used Cox regression to estimate multivariable-adjusted HRs for death according to nut consumption. In secondary analyses, we evaluated associations of nut consumption with cause-specific mortality. Results: During a mean follow-up of 9.6 y, there were 2732 deaths. The mean (±SD) age at baseline was 66.6 ± 9.3 y. Median nut consumption was 1 serving/wk. Multivariable-adjusted HRs (95% CIs) were 1.0 (reference), 0.92 (0.83, 1.01), 0.85 (0.76, 0.96), 0.86 (0.75, 0.98), and 0.74 (0.63, 0.87) for nut consumption of never or <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and ≥5 servings/wk, respectively (P-linear trend < 0.0001), after adjustment for age, body mass index, alcohol use, smoking, exercise, prevalent diabetes and hypertension, and intakes of energy, saturated fat, fruit and vegetables, and red meat. In a secondary analysis, results were consistent for cardiovascular disease mortality but only suggestive and non-statistically significant for coronary artery disease and cancer mortality. Conclusion: Our data are consistent with an inverse association between nut consumption and the risk of all-cause and cardiovascular disease mortality in U.S. male physicians. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic data on the role of diet in acute pancreatitis are sparse. Objective: We examined the association of total fish consumption, as well as of consumption of fatty fish and lean fish separately, with risk of non-gallstone-related acute pancreatitis. Design: We used data from 2 prospective cohorts, the Cohort of Swedish Men and the Swedish Mammography Cohort, that included 39,267 men and 32,191 women who were aged 45-84 y at the start of a 13-y follow-up period (1998-2010). Fish consumption was assessed by using a food-frequency questionnaire at baseline, and cases of incident non-gallstone-related acute pancreatitis were identified by linkage to the Swedish National Patient Register. HRs were estimated by using Cox proportional hazard models. Results: During a total follow-up of 860,176 person-years, 320 cases (209 cases in men and 111 cases in women) of incident non-gallstone-related acute pancreatitis were identified. We observed that total fish consumption ≤ 2.0-3.0 servings/wk was associated with a significantly decreased risk of the disease (P-nonlinearity = 0.017). In comparison with 0.9 servings/wk, multivariable-adjusted HRs were 0.86 (95% CI: 0.76, 0.96), 0.77 (95% CI: 0.62, 0.96), and 0.85 (95% CI: 0.65, 1.10) for 1.4, 2.4, and 3.5 servings/wk, respectively. In the analysis of fatty fish and lean fish, we observed that the consumption of each subtype had a similarly shaped association with risk of non-gallstone-related acute pancreatitis as that observed for total fish consumption, although neither was significant. Multivariable-adjusted HRs were 0.83 for fatty fish (95% CI: 0.65, 1.04) and 0.87 for lean fish (95% CI: 0.69, 1.11) when 0.6-2.0 servings/wk was compared with ≤0.5 servings/wk. Conclusion: Our data suggest that the consumption of total fish (fatty fish and lean fish combined) may be associated with decreased risk of non-gallstone-related acute pancreatitis. The Swedish Mammography Cohort was registered at clinicaltrials.gov as NCT01127698. The Cohort of Swedish Men was registered at clinicaltrials.gov as NCT01127711. [ABSTRACT FROM AUTHOR]

Background: Health concerns have been raised about rice consumption, which may significantly contribute to arsenic exposure. However, little is known regarding whether habitual rice consumption is associated with cardiovascular disease (CVD) risk. Objective: We examined prospectively the association of white rice and brown rice consumption with CVD risk. Design: We followed a total of 207,556 women and men [73,228 women from the Nurses' Health Study (1984-2010), 92,158 women from the Nurses' Health Study II (1991-2011), and 42,170 men from the Health Professionals Follow-Up Study (1986-2010)] who were free of CVD and cancer at baseline. Validated semiquan-titative food-frequency questionnaires were used to assess consumption of white rice, brown rice, and other food items. Fatal and nonfatal CVD (coronary artery disease and stroke) was confirmed by medical records or self-reports. Results: During 4,393,130 person-years of follow-up, 12,391 cases of CVD were identified. After adjustment for major CVD risk factors, including demographics, lifestyle, and other dietary intakes, rice consumption was not associated with CVD risk. The multivariable-adjuted HR of developing CVD comparing ≥5 servings/wk with <1 serving/wk was 0.98 (95% CI: 0.84, 1.14) for white rice, 1.01 (0.79, 1.28) for brown rice, and 0.99 (0.90, 1.08) for total rice. To minimize the potential impact of racial difference in rice consumption, we restricted the analyses to whites only and obtained similar results: the HRs of CVD for ≥5 servings/wk compared with <1 serving/wk were 1.04 (95% CI: 0.88, 1.22) for white rice and 1.01 (0.78, 1.31) for brown rice. Conclusions: Greater habitual consumption of white rice or brown rice is not associated with CVD risk. These findings suggest that rice consumption may not pose a significant CVD risk among the U.S. population when consumed at current amounts. More prospective studies are needed to explore these associations in other populations. [ABSTRACT FROM AUTHOR]

Background: Biochemical evidence has linked the coordinate control of fatty acid (FA) synthesis with the activity of stearoyl-CoA desaturase-1 (SCD1). The ratio of 16:1n-7 to 16:0 [SCD1(16)] in plasma triacylglycerol FA has been used as an index to reflect liver SCD1(16) activity and has been proposed as a biomarker of FA synthesis, although this use has not been validated by comparison with isotopically measured de novo lipogenesis (DNLMeas). Objective: We investigated plasma lipid 16:1n-7 and FA indexes of elongation and desaturation in relation to lipogenesis. Design: In this cross-sectional investigation of metabolism, 24 overweight adults, who were likely to have elevated DNL, consumed D2O for 10 d and had liver fat (LF) measured by magnetic resonance spec-troscopy. Very-low-density lipoprotein (VLDL)-triacylglycerols and plasma free FA [nonesterified fatty acids (NEFAs)] were analyzed by using gas chromatography for the FA composition (molar percentage) and gas chromatography-mass spectrometry and gas chromatography-combustion isotope ratio mass spectrometry for deuterium enrichment. Results: In all subjects, VLDL-triacylglycerol 16:1n-7 was significantly (P < 0.01) related to DNLMeas (r = 0.56), liver fat (r = 0.53), and adipose insulin resistance (r = 0.56); similar positive relations were shown with the SCD1(16)) index, and the pattern in NEFAs echoed that of VLDL-triacylglycerols. Compared with subjects with low LF (3.1 ± 2.7%; n = 11), subjects with high LF (18.4 ± 3.6%; n = 13) exhibited a 45% higher VLDL-triacylglycerol 16:1n-7 molar percentage (P < 0.01), 16% of subjects had lower 18:2n-6 (P = 0.01), and 27% of subjects had higher DNL as assessed by using a published DNL index (ratio of 16:0 to 18:2n-6; P = 0.03), which was isotopically confirmed by DNLMEAS (increased 2.5-fold; P < 0.01). Compared with 16:0 in the diet, the low amount of dietary 16:1n-7 in VLDL-triacylglycerols corresponded to a stronger signal of elevated DNL. Conclusion: The current data provide support for the use of the VLDL-triacylglycerol 16:1n-7 molar percentage as a biomarker for elevated liver fat when isotope use is not feasible; however, larger-scale confirmatory studies are needed. This trial was registered at clinicaltrials.gov as NCT01371396. [ABSTRACT FROM AUTHOR]

Background: Unlike experimental results, epidemiologic studies that used dietary questionnaires were not convincing as regards the relations between dietary fatty acids (FAs) and risk of colorectal cancer (CRC). The FA composition of adipose tissue, which is considered to be an indicator of dietary intake over 2-3 y because of the slow turnover rate, appears promising but has so far been rarely used to explore the relation between CRC and exogenous or endogenously produced FAs. Objective: In this case-control study, we aimed to investigate associations between risk of CRC and the FA composition of subcutaneous adipose tissue and product-to-precursor ratios as indexes of enzymatic activities. Design: From 2008 to 2011, we recruited 203 cases with newly diagnosed CRC and elective surgery with a curative intent and 223 control subjects with planned abdominal surgery for benign disease and no history of CRC or polyp resection. During surgery, abdominal subcutaneous adipose tissue samples were optimally collected, stored, and analyzed by using high-performance gas chro-matography. Multivariate logistic regression was used to estimate ORs for CRC in relation to individual FAs divided into tertiles according to the FA distribution in controls. Results: After adjustment, significant positive associations with CRC risk were observed in highest compared with lowest tertiles of 16:1n-9 (OR: 1.75; 95% CI: 1.00, 3.06; P-trend = 0.045), 20:3n-6 (OR: 1.79; 95% CI: 1.01, 3.17; P-trend = 0.038), 22:5n-3 (OR: 1.82; 95% CI: 1.06, 3.12; P-trend = 0.023), and the ratio of 18:2n-6 to 18:3n-3 (OR: 2.34; 95% CI: 1.37, 3.98; P-trend = 0.001). Significant inverse associations were observed for 18:3n-3 (OR: 0.48; 95% CI: 0.29, 0.81; P-trend = 0.007). Several product-to-precursor ratios showed significant differences between cases and controls in particular ratios that reflected elongase 2/5 activity. Conclusions: CRC patients presented higher concentrations of some FAs but lower concentrations of a-linolenic acid in their subcutaneous adipose tissue than did controls. These results may reflect both dietary patterns and altered FA metabolism but require mechanistic explorations. This study was registered at clinicaltrials.gov as NCT01966081. [ABSTRACT FROM AUTHOR]

Background: Although a higher consumption of alcohol, which is a methyl-group antagonist, was previously associated with colorectal cancer risk, mechanisms remain poorly understood. Objective: We hypothesized that excess alcohol consumption might increase risk of colorectal carcinoma with hypomethylation of insulin-like growth factor 2 (IGF2) differentially methylated region-0 (DMR0), which was previously associated with a worse prognosis. Design: With the use of a molecular pathologic epidemiology database in 2 prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association between alcohol intake and incident colorectal cancer according to the tumor methylation level of IGF2 DMR0. Duplication-method Cox proportional cause-specific hazards regression for competing risk data were used to compute HRs and 95% CIs. In addition, we investigated intakes of vitamin B-6, vitamin B-12, methionine, and folate as exposures. Results: During 3,206,985 person-years of follow-up, we identified 993 rectal and colon cancer cases with an available tumor DNA methylation status. Compared with no alcohol consumption, the consumption of =15 g alcohol/d was associated with elevated risk of colorectal cancer with lower levels of IGF2 DMR0 methylation [within the first and second quartiles: HRs of 1.55 (95% CI: 1.08, 2.24) and 2.11 (95% CI: 1.44, 3.07), respectively]. By contrast, alcohol consumption was not associated with cancer with higher levels of IGF2 DMR0 methylation. The association between alcohol and cancer risk differed significantly by IGF2 DMR0 methylation level (P-heterogeneity = 0.006). The association of vitamin B-6, vitamin B-12, and folate intakes with cancer risk did not significantly differ according to IGF2 DMR0 methylation level (P-heterogeneity > 0.2). Conclusions: Higher alcohol consumption was associated with risk of colorectal cancer with IGF2 DMR0 hypomethylation but not risk of cancer with high-level IGF2 DMR0 methylation. The association between alcohol intake and colorectal cancer risk may differ by tumor epigenetic features. [ABSTRACT FROM AUTHOR]

Mental health disorders (MHDs), mild traumatic brain injury (mTBI), and alcohol use disorder (AUD) are endemic among recent Veterans, resulting in a population with heterogeneous, co-occurring conditions. While alcohol craving negatively affects rehabilitation and leads to relapse, no studies have examined alcohol craving among Veterans with co-occurring MHDs and mTBI. The purpose of this preliminary cohort study is to describe alcohol craving in a convenience sample of Iraq and Afghanistan Veterans (n = 48), including those exposed to traumatic events and experiencing active symptoms. Veterans completed weekly telephone interviews that included the Alcohol Use Disorder Identification Test, consumption questions (AUDIT-C) (week 1) and the Penn Alcohol Craving Scale (PACS) (weeks 1-6). Sixty percent of the sample screened positive on the AUDIT-C for probable AUD. Using Rasch analysis, the person separation reliability of the PACS was strong (0.87) among AUDIT-C positive Veterans. Higher PACS scores were reported among AUDITC positive versus AUDIT-C negative Veterans (mixed effects analysis, p < 0.001). PACS scores were higher among AUDIT-C positive Veterans with MHDs with and without mTBI versus AUDIT-C positive combat comparison Veterans (pairwise comparison, p < 0.001). Rates of hazardous alcohol use are high among Iraq and Afghanistan conflict Veterans and suggest that alcohol craving is elevated among those with MHDs with and without mTBI. [ABSTRACT FROM AUTHOR]