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1.
Am J Clin Nutr ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33829249

RESUMO

BACKGROUND: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. OBJECTIVES: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. MEDTHODS: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. RESULTS: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. CONCLUSIONS: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.

2.
Ugeskr Laeger ; 183(14)2021 Apr 05.
Artigo em Dinamarquês | MEDLINE | ID: mdl-33832554

RESUMO

Alcohol is carcinogenic to humans. There is convincing evidence that alcohol intake increases the risk of cancers of the mouth, pharynx, larynx, oesophagus (squamous cell carcinoma), liver and colorectum, and breast cancer among postmenopausal women. Research indicates that no safe lower limit of intake exists. The risk increases with the amount of alcohol, and in most studies all types of alcohol, like wine, beer and spirits increase the risk. A substantial number of cancer cases could be prevented by a reduction in alcohol intake.

3.
Am J Prev Med ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33775511

RESUMO

INTRODUCTION: Modifiable lifestyle behaviors represent a central target for public health interventions. This study investigates the association between adherence to 4 modifiable lifestyle recommendations and all-cause, cancer, or cardiovascular disease mortality. METHODS: Investigators used data from the Danish Diet, Cancer and Health cohort (1993-2013; N=54,276). Lifestyle recommendations included smoking (never smoking), diet (adherence to 6 national food-based dietary guidelines), alcohol consumption (≤7 units per week for women and ≤14 units per week for men), and physical activity (≥30 minutes per day of moderate-to-vigorous leisure-time physical activity). Pseudo-values were used to estimate the adjusted risk differences and 95% CIs for all-cause, cancer, or cardiovascular disease mortality. Data were analyzed in 2019-2020. RESULTS: A total of 8,860 participants died during a median follow-up of 17.0 years. Adherence to all modifiable lifestyle recommendations was associated with an 18.46% (95% CI= -20.52, -16.41) lower absolute risk of all-cause mortality than no adherence. Never smokers had a 13.19% (95% CI= -13.95, -12.44) lower risk, those adhering to dietary guidelines (diet score ≥5) had a 7.52% (95% CI= -8.89, -6.14) lower risk, and those adhering to recommended levels of alcohol (2.11%, 95% CI= -2.75, -1.48) and physical activity (1.58%, 95% CI= -2.20, -1.00) had a lower risk than those who did not adhere. Stronger associations were observed in men than in women and in older than in middle-aged participants. CONCLUSIONS: Findings suggest that adherence to modifiable lifestyle recommendations is associated with a lower risk of mortality from all causes, cancer, and cardiovascular disease, underlining the importance of supporting adherence to national guidelines for lifestyle recommendations.

4.
Public Health Nutr ; : 1-18, 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33749573

RESUMO

OBJECTIVE: To study the association between organic food consumption and lifestyle, socio-demographics, and dietary habits. DESIGN: Cohort participants completed detailed questionnaires about organic food consumption, diet, and lifestyle between 1999 and 2002. Polytomous logistic regression models were used to estimate the association between organic food consumption, and lifestyle, socio-demographics, and dietary habits. SETTING: This cross-sectional study uses data from the Danish Diet, Cancer and Health cohort. PARTICIPANTS: A total of 43,209 men and women aged between 54 and 73 years were included in the study. RESULTS: Overall, 15% reported never consuming organic food, 39% had low organic food consumption, 37% had medium organic food consumption and 10% had high organic food consumption. The relative risk of consuming organic food versus never consuming organic food was highest among women, persons with body mass index <25 kg/m2, persons with low alcohol intake, persons participating in sports, persons who did not smoke or were former smokers, and among persons who adhered to the Danish national dietary guidelines. Associations were more distinct with higher levels of organic food consumption. CONCLUSION: Based on a historical cohort of Danish adults, organic food consumption was associated with a generally healthy lifestyle, more favorable socio-demographics, and dietary habits. These findings have to be considered in the adjustment strategy for future studies linking organic food consumption with health outcomes.

5.
Carcinogenesis ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33780524

RESUMO

Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino-acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case-control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs: N ε-(carboxy-methyl)lysine (CML), N ε-(carboxy-ethyl)lysine (CEL) and N δ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured by ultra-performance liquid chromatography tandem mass-spectrometry in baseline samples collected from 1,378 incident primary colorectal cancer cases and 1,378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5vs.Q1=0.40, 95%CI:0.27-0.59), MG-H1 (ORQ5vs.Q1=0.73, 95%CI:0.53 - 1.00) and total AGEs (OR Q5vs.Q1=0.52, 95%CI:0.37 - 0.73) whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5vs.Q1=1.91, 95%CI:1.31-2.79). The associations observed did not differ by sex, or by tumour anatomical subsite. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed.

6.
BMC Med ; 19(1): 81, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33781249

RESUMO

BACKGROUND: Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors. RESULTS: After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01-1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03-1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01-1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes. CONCLUSIONS: These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations.

7.
Int J Epidemiol ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33755122

RESUMO

BACKGROUND: The role of obesity and weight change in breast-cancer development is complex and incompletely understood. We investigated long-term weight change and breast-cancer risk by body mass index (BMI) at age 20 years, menopausal status, hormone replacement therapy (HRT) and hormone-receptor status. METHODS: Using data on weight collected at three different time points from women who participated in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the association between weight change from age 20 years until middle adulthood and risk of breast cancer. RESULTS: In total, 150 257 women with a median age of 51 years at cohort entry were followed for an average of 14 years (standard deviation = 3.9) during which 6532 breast-cancer cases occurred. Compared with women with stable weight (±2.5 kg), long-term weight gain >10 kg was positively associated with postmenopausal breast-cancer risk in women who were lean at age 20 [hazard ratio (HR) = 1.42; 95% confidence interval 1.22-1.65] in ever HRT users (HR = 1.23; 1.04-1.44), in never HRT users (HR = 1.40; 1.16-1.68) and in oestrogen-and-progesterone-receptor-positive (ER+PR+) breast cancer (HR = 1.46; 1.15-1.85). CONCLUSION: Long-term weight gain was positively associated with postmenopausal breast cancer in women who were lean at age 20, both in HRT ever users and non-users, and hormone-receptor-positive breast cancer.

8.
J Nutr ; 151(3): 666-674, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33561273

RESUMO

BACKGROUND: Pancreatic cancer is a highly deadly disease with a poor prognosis. There is limited knowledge about prevention of the disease; thus, identification of risk factors is important to reduce the disease incidence. OBJECTIVE: The aim of the present study was to prospectively investigate associations between incidence of pancreatic cancer and whole-grain intake measured in 2 ways: as whole-grain product intake (g whole-grain products/d) and as whole-grain intake (grams of whole grains/d). Moreover, the intake of subgroups of these was also investigated: whole-grain products (rye bread, whole-grain bread, and oatmeal/muesli) and cereals (rye, wheat, and oats). METHODS: In total, 55,995 Danish adults aged 50-64 y, of whom 446 developed pancreatic cancer (17.5 y mean follow-up), were included in the study. Detailed information on daily intake of whole-grain products was available from a validated self-administered FFQ, and intake of whole-grain cereals (wheat, rye, and oats) was estimated using information from a 24-h dietary recall. The association between the whole-grain exposures and incidence of pancreatic cancer was investigated by Cox regression analyses adjusted for potential confounders. RESULTS: Total whole-grain product intake was associated with a 7% lower incidence of pancreatic cancer per serving (50 g/d) (HR: 0.93; 95% CI: 0.86, 1.00), and in the sex-specific analyses, an inverse association was found only in men. No association was found for total whole-grain intake (per 16-g serving size; HR: 0.96; 95% CI: 0.89, 1.03). When investigating specific whole-grain products and cereals individually, none were alone associated with lower incidence of pancreatic cancer. CONCLUSION: Our findings indicate that intake of whole grains is associated with lower risk of pancreatic cancer in middle-aged men. Consuming ample amounts of whole grains may prove beneficial in terms of lowering pancreatic cancer risk.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33335022

RESUMO

BACKGROUND: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives. METHODS: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure. RESULTS: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679-0.721]). Our model had slightly improved discrimination (0.714 [0.694-0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025. CONCLUSIONS: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population. IMPACT: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.

10.
Diabetes Care ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33203707

RESUMO

OBJECTIVE: Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants. RESULTS: We identified 11 genomic regions associated with plasma vitamin C (P < 5 × 10-8), with the strongest signal at SLC23A1, and 10 novel genetic loci including SLC23A3, CHPT1, BCAS3, SNRPF, RER1, MAF, GSTA5, RGS14, AKT1, and FADS1. Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding FADS1 variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10). CONCLUSIONS: These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.

11.
PLoS Med ; 17(10): e1003394, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33064751

RESUMO

BACKGROUND: Prior research suggested a differential association of 25-hydroxyvitamin D (25(OH)D) metabolites with type 2 diabetes (T2D), with total 25(OH)D and 25(OH)D3 inversely associated with T2D, but the epimeric form (C3-epi-25(OH)D3) positively associated with T2D. Whether or not these observational associations are causal remains uncertain. We aimed to examine the potential causality of these associations using Mendelian randomisation (MR) analysis. METHODS AND FINDINGS: We performed a meta-analysis of genome-wide association studies for total 25(OH)D (N = 120,618), 25(OH)D3 (N = 40,562), and C3-epi-25(OH)D3 (N = 40,562) in participants of European descent (European Prospective Investigation into Cancer and Nutrition [EPIC]-InterAct study, EPIC-Norfolk study, EPIC-CVD study, Ely study, and the SUNLIGHT consortium). We identified genetic variants for MR analysis to investigate the causal association of the 25(OH)D metabolites with T2D (including 80,983 T2D cases and 842,909 non-cases). We also estimated the observational association of 25(OH)D metabolites with T2D by performing random effects meta-analysis of results from previous studies and results from the EPIC-InterAct study. We identified 10 genetic loci associated with total 25(OH)D, 7 loci associated with 25(OH)D3 and 3 loci associated with C3-epi-25(OH)D3. Based on the meta-analysis of observational studies, each 1-standard deviation (SD) higher level of 25(OH)D was associated with a 20% lower risk of T2D (relative risk [RR]: 0.80; 95% CI 0.77, 0.84; p < 0.001), but a genetically predicted 1-SD increase in 25(OH)D was not significantly associated with T2D (odds ratio [OR]: 0.96; 95% CI 0.89, 1.03; p = 0.23); this result was consistent across sensitivity analyses. In EPIC-InterAct, 25(OH)D3 (per 1-SD) was associated with a lower risk of T2D (RR: 0.81; 95% CI 0.77, 0.86; p < 0.001), while C3-epi-25(OH)D3 (above versus below lower limit of quantification) was positively associated with T2D (RR: 1.12; 95% CI 1.03, 1.22; p = 0.006), but neither 25(OH)D3 (OR: 0.97; 95% CI 0.93, 1.01; p = 0.14) nor C3-epi-25(OH)D3 (OR: 0.98; 95% CI 0.93, 1.04; p = 0.53) was causally associated with T2D risk in the MR analysis. Main limitations include the lack of a non-linear MR analysis and of the generalisability of the current findings from European populations to other populations of different ethnicities. CONCLUSIONS: Our study found discordant associations of biochemically measured and genetically predicted differences in blood 25(OH)D with T2D risk. The findings based on MR analysis in a large sample of European ancestry do not support a causal association of total 25(OH)D or 25(OH)D metabolites with T2D and argue against the use of vitamin D supplementation for the prevention of T2D.

12.
Int J Cancer ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33128820

RESUMO

To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.

13.
Acta Oncol ; : 1-7, 2020 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-33103532

RESUMO

BACKGROUND: Vitamin D has a role in bone turnover and potentially bone-metastatic spread of prostate cancer (PCa). The aim of this observational study was to address the association between levels of serum vitamin D, diagnosis of PCa and subsequent mortality in men who underwent a biopsy of the prostate. METHODS: All men who underwent prostatic biopsy in the Danish PCa Registry (DaPCaR) and who had a serum vitamin D measurement during the period 2004 to 2010 (n = 4,065) were identified. Men were categorized by clinical cut-offs based on seasonally adjusted serum vitamin D levels in <25 (deficient), 25-50 (insufficient), 50-75 (sufficient) and >75 nmol/L (high) serum vitamin D. Logistic regression model for association between vitamin D and risk of PCa diagnosis and multivariate survival analyses were applied. RESULTS: No association between serum vitamin D and risk of PCa was found. Overall survival was lowest for serum vitamin D deficiency and a significantly higher PCa specific mortality (HR: 2.37, 95%CI: 1.45-3.90, p < .001) and other cause mortality (HR: 2.08, 95%CI: 1.33-3.24, p = .001) was found for PCa patients with serum vitamin D deficiency compared to serum vitamin D sufficiency. CONCLUSION: No association was found between serum vitamin D categories and risk of PCa in men who underwent biopsy of the prostate. Men with PCa and serum vitamin D deficiency had a higher overall and PCa specific mortality compared to men with a sufficient level of serum vitamin D.

14.
Diabetes Care ; 43(11): 2660-2667, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32868270

RESUMO

OBJECTIVE: There is sparse evidence for the association of suitable food substitutions for red and processed meat on the risk of type 2 diabetes. We modeled the association between replacing red and processed meat with other protein sources and the risk of type 2 diabetes and estimated its population impact. RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer (EPIC)-InterAct case cohort included 11,741 individuals with type 2 diabetes and a subcohort of 15,450 participants in eight countries. We modeled the replacement of self-reported red and processed meat with poultry, fish, eggs, legumes, cheese, cereals, yogurt, milk, and nuts. Country-specific hazard ratios (HRs) for incident type 2 diabetes were estimated by Prentice-weighted Cox regression and pooled using random-effects meta-analysis. RESULTS: There was a lower hazard for type 2 diabetes for the modeled replacement of red and processed meat (50 g/day) with cheese (HR 0.90, 95% CI 0.83-0.97) (30 g/day), yogurt (0.90, 0.86-0.95) (70 g/day), nuts (0.90, 0.84-0.96) (10 g/day), or cereals (0.92, 0.88-0.96) (30 g/day) but not for replacements with poultry, fish, eggs, legumes, or milk. If a causal association is assumed, replacing red and processed meat with cheese, yogurt, or nuts could prevent 8.8%, 8.3%, or 7.5%, respectively, of new cases of type 2 diabetes. CONCLUSIONS: Replacement of red and processed meat with cheese, yogurt, nuts, or cereals was associated with a lower rate of type 2 diabetes. Substituting red and processed meat by other protein sources may contribute to the prevention of incident type 2 diabetes in European populations.

15.
Int J Cancer ; 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32838475

RESUMO

Low selenium status may be associated with increased risk of prostate cancer (PC), particularly aggressive PC, and variation in selenoprotein genes may constitute an important modifying factor. We aimed to investigate the association between two selenium status biomarkers [toenail selenium, plasma selenoprotein P (SELENOP)] and risk of advanced, high-grade and advanced-stage PC. We further studied whether variations in selenoprotein genes were associated with PC risk and selenium biomarker concentrations. In the "Diet, Cancer and Health" cohort, 27 178 men aged 50 to 65 years were enrolled from 1993 to 1997. Between baseline and 2012, 1160 cohort participants were diagnosed with advanced PC; among these 462 had high-grade and 281 had advanced-stage disease at diagnosis. Each case was risk set-matched to one control. Toenail selenium and plasma SELENOP concentrations were measured by neutron activation analysis and a SELENOP-ELISA, respectively, and genotyping was performed for 27 selected single nucleotide polymorphisms (SNPs) in 12 selenium pathway genes (including seven selenoproteins) by allele-specific PCR. Toenail selenium and circulating SELENOP concentrations were not associated with advanced, high-grade or advanced-stage PC. After adjustment for multiple testing, none of the genes were associated with PC risk. Neither toenail selenium nor plasma SELENOP was associated with advanced, high-grade or advanced-stage PC.

16.
Eur J Epidemiol ; 35(11): 1057-1067, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32710289

RESUMO

Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose-response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03-1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02-1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04-1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01-1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02-1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose-response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.

17.
BMC Med ; 18(1): 187, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32698845

RESUMO

BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer in men. Metabolomics can potentially provide new insights into the aetiology of prostate cancer by identifying new metabolic risk factors. This study investigated the prospective association between plasma metabolite concentrations and prostate cancer risk, both overall and by stratifying for disease aggressiveness and baseline age. METHODS: In a case-control study nested in the Northern Sweden Health and Disease Study, pre-diagnostic concentrations of 148 plasma metabolites were determined using targeted mass spectrometry- and nuclear magnetic resonance-based metabolomics in 777 prostate cancer cases (follow-up ≥ 5 years) and 777 matched controls. Associations between prostate cancer risk and metabolite concentrations were investigated using conditional logistic regression conditioned on matching factors (body mass index, age and sample storage time). Corrections for multiple testing were performed using false discovery rate (20%) and Bonferroni. Metabolomics analyses generated new hypotheses, which were investigated by leveraging food frequency questionnaires (FFQs) and oral glucose tolerance tests performed at baseline. RESULTS: After correcting for multiple testing, two lysophosphatidylcholines (LPCs) were positively associated with risk of overall prostate cancer (all ages and in older subjects). The strongest association was for LPC C17:0 in older subjects (OR = 2.08; 95% CI 1.45-2.98; p < 0.0001, significant also after the Bonferroni correction). Observed associations with risk of overall prostate cancer in younger subjects were positive for glycine and inverse for pyruvate. For aggressive prostate cancer, there were positive associations with six glycerophospholipids (LPC C17:0, LPC C20:3, LPC C20:4, PC ae C38:3, PC ae C38:4 and PC ae C40:2), while there was an inverse association with acylcarnitine C18:2. Moreover, plasma LPC C17:0 concentrations positively correlated with estimated dietary intake of fatty acid C17:0 from the FFQs. The associations between glycerophospholipids and prostate cancer were stronger in case-controls with normal glucose tolerance. CONCLUSIONS: Several glycerophospholipids were positively associated with risk of overall and aggressive prostate cancer. The strongest association was observed for LPC C17:0. The associations between glycerophospholipids and prostate cancer risk were stronger in case-controls with normal glucose tolerance, suggesting a link between the glucose metabolism status and risk of prostate cancer.

18.
Eur J Nutr ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32500314

RESUMO

PURPOSE: The aim was to analyze the intake of whole grain (WG) and associations with lifestyle and demographics in a newly established cohort of Danish adults. METHODS: Between 2015 and 2019, Danes were enrolled into The Diet, Cancer and Health-Next Generations cohort. A total of 38,553 persons were included in the current cross-sectional study, where all completed a 376-item food frequency questionnaire, a lifestyle questionnaire, and a physical examination in a study center where physical measurements and biological samples were collected. RESULTS: The median intake of WG was 79 g/10 mega joule (MJ) and 54% of the participants consumed the amount of WG recommended in Denmark, which is 75 g/10 MJ. The probability of consuming the recommended amount of WG was highest among men, persons < 30 years, students, persons with body mass index (BMI) < 25 kg/m2, persons participating in sports, who did not exceed the recommended maximum intake of alcohol and did not smoke. The probability of having a low intake of WG defined as < 25 g/10 MJ was highest among persons with short education, BMI ≥ 25 kg/m2, persons not participating in sports, persons having an alcohol intake above the recommended maximum level and persons being active smokers. CONCLUSION: The median intake of WG was 79 g/10 MJ. The probability of consuming at least 75 g WG/10 MJ was highest among persons who also adhered to healthy lifestyle measured by other factors. Only 6% of the cohort participants consumed < 25 g WG/10 MJ, these persons were more likely to have a general less healthy lifestyle.

19.
Am J Clin Nutr ; 111(4): 864-876, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097450

RESUMO

BACKGROUND: A whole-grain (WG)-rich diet has shown to have potential for both prevention and treatment of the metabolic syndrome (MetS), which is a cluster of risk factors that increase the risk of type 2 diabetes and cardiovascular disease. Different WGs may have different health effects. WG rye, in particular, may improve glucose homeostasis and blood lipids, possibly mediated through fermentable dietary fiber and lignans. Recent studies have also suggested a crucial role of the gut microbiota in response to WG. OBJECTIVES: The aim was to investigate WG rye, alone and with lignan supplements [secoisolariciresinol diglucoside (SDG)], and WG wheat diets on glucose tolerance [oral-glucose-tolerance test (OGTT)], other cardiometabolic outcomes, enterolignans, and microbiota composition. Moreover, we exploratively evaluated the role of gut microbiota enterotypes in response to intervention diets. METHODS: Forty men with MetS risk profile were randomly assigned to WG diets in an 8-wk crossover study. The rye diet was supplemented with 280 mg SDG at weeks 4-8. Effects of treatment were evaluated by mixed-effects modeling, and effects on microbiota composition and the role of gut microbiota as a predictor of response to treatment were analyzed by random forest plots. RESULTS: The WG rye diet (± SDG supplements) did not affect the OGTT compared with WG wheat. Total and LDL cholesterol were lowered (-0.06 and -0.09 mmol/L, respectively; P < 0.05) after WG rye compared with WG wheat after 4 wk but not after 8 wk. WG rye resulted in higher abundance of Bifidobacterium [fold-change (FC) = 2.58, P < 0.001] compared with baseline and lower abundance of Clostridium genus compared with WG wheat (FC = 0.54, P = 0.02). The explorative analyses suggest that baseline enterotype is associated with total and LDL-cholesterol response to diet. CONCLUSIONS: WG rye, alone or with SDG supplementation, compared with WG wheat did not affect glucose metabolism but caused transient LDL-cholesterol reduction. The effect of WG diets appeared to differ according to enterotype. This trial was registered at www.clinicaltrials.gov as NCT02987595.


Assuntos
Lignanas/metabolismo , Síndrome Metabólica/dietoterapia , Secale/metabolismo , Triticum/metabolismo , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Glicemia/metabolismo , Doenças Cardiovasculares/complicações , Colesterol/metabolismo , Estudos Cross-Over , Suplementos Nutricionais/análise , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Humanos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Síndrome Metabólica/microbiologia , Pessoa de Meia-Idade , Fatores de Risco , Grãos Integrais/metabolismo
20.
Mult Scler Relat Disord ; 40: 101968, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32035368

RESUMO

BACKGROUND: Multiple sclerosis (MS) onset is commonly observed in adults aged 20-50 years of age. The incidence rate of MS-onset after age 50, late-onset MS, has increased along with the observed overall increase in MS incidence rate in the past 60 years. In general, the aetiology of MS is largely acknowledged to involve a complex interrelation of environmental and modifiable lifestyle risk factors in genetically susceptible individuals. Smoking is an established risk factor, while the role of the diet in the aetiology of MS remains inconclusive. However, even less is known about the role of diet and smoking in the aetiology of late-onset MS as this subgroup of patients has not gained much attention in the scientific literature. Therefore, the objective of this study was to investigate the association between diet quality and the hazards of late-onset MS diagnosis in relation to smoking habits, thus attempting to identify high-risk individuals. METHODS: The study was a prospective cohort study based on the Danish cohort Diet, Cancer and Health including middle-aged individuals (50-64 years) born and residing in Denmark. Cox' proportional hazards models were used to estimate the hazard ratios (HR) for tertiles of diet quality, assessed by means of the Alternative Healthy Eating Index-2010. Information on time-at-risk and diagnosis of MS was collected based on linked information from the Danish Civil Registration System and Danish National Patient Registry. Additionally, a stratified analysis according to smoking status (current smokers, former smokers and never smokers) was conducted while adjusting for sex. RESULTS: A total of 56,867 individuals were followed for a median of 20.4 years. During follow-up, 124 individuals were diagnosed with late-onset MS. No statistically significant association was found between diet quality at baseline and the hazard of MS diagnosis in adjusted analyses (HR highest vs lowest diet quality tertile: 0.79; 95%CI: 0.49-1.27, Test for trend: p = 0.22). Smoking status did not modify the association. CONCLUSION: In this cohort of middle-aged Danes, diet quality was neither statistically significantly associated with the hazards of late-onset MS diagnosis in the entire sample, nor in sub-groups of current smokers, former smokers or never smokers.

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