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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.
BMC Med ; 19(1): 101, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33926456

RESUMO

BACKGROUND: The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study. METHODS: Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants. RESULTS: After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR1-sd 1.50, 95% CI 1.30-1.74), WC (OR1-sd 1.46, 95% CI 1.27-1.69), and WHR (OR1-sd 1.54, 95% CI 1.33-1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR1-sd: 1.26, 95% CI 1.07-1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06-0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05-0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32-0.87, p = 0.01). CONCLUSIONS: Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33901663

RESUMO

BACKGROUND & AIMS: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. METHODS: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5,069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. RESULTS: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta-carotene, fruit, fibre, non-white bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in NLCS, for which a meta-analysis was performed, namely alcohol (summary HR per 1 SD increment in intake: 1.07; 95%CI:1.04-1.09), liquor/spirits (1.04; 1.02-1.06), wine (1.04;1.02-1.07), beer/cider (1.06;1.04-1.08), milk (0.95;0.93-0.98), cheese (0.96;0.94-0.99), calcium (0.93;0.90-0.95), phosphorus (0.92;0.90-0.95), magnesium (0.95;0.92-0.98), potassium (0.96;0.94-0.99), riboflavin (0.94;0.92-0.97), beta-carotene (0.96;0.93-0.98), and total protein (0.94;0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. CONCLUSIONS: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta-carotene and total protein.

4.
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.

5.
Int J Cancer ; 148(11): 2759-2773, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33554339

RESUMO

Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.

6.
Nutrients ; 13(2)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530330

RESUMO

We investigated associations of habitual dietary intake with the taxonomic composition and diversity of the human gut microbiota in 222 Koreans aged 18-58 years in a cross-sectional study. Gut microbiota data were obtained by 16S rRNA gene sequencing on DNA extracted from fecal samples. The habitual diet for the previous year was assessed by a food frequency questionnaire. After multivariable adjustment, intake of several food groups including vegetables, fermented legumes, legumes, dairy products, processed meat, and non-alcoholic beverages were associated with major phyla of the gut microbiota. A dietary pattern related to higher α-diversity (HiαDP) derived by reduced rank regression was characterized by higher intakes of fermented legumes, vegetables, seaweeds, and nuts/seeds and lower intakes of non-alcoholic beverages. The HiαDP was positively associated with several genera of Firmicutes such as Lactobacillus, Ruminococcus, and Eubacterium (all p < 0.05). Among enterotypes identified by principal coordinate analysis based on the ß-diversity, the Ruminococcus enterotype had higher HiαDP scores and was strongly positively associated with intakes of vegetables, seaweeds, and nuts/seeds, compared to the two other enterotypes. We conclude that a plant- and fermented food-based diet was positively associated with some genera of Firmicutes (e.g., Lactobacillus, Ruminococcus, and Eubacterium) reflecting better gut microbial health.


Assuntos
Bactérias/classificação , Dieta , Ingestão de Alimentos , Microbioma Gastrointestinal , Adolescente , Adulto , Bactérias/genética , Biodiversidade , Estudos Transversais , Laticínios , Fibras na Dieta , Fezes/microbiologia , Comportamento Alimentar , Feminino , Alimentos e Bebidas Fermentados , Firmicutes/classificação , Firmicutes/genética , Microbioma Gastrointestinal/genética , Humanos , Masculino , Pessoa de Meia-Idade , Nozes , RNA Ribossômico 16S/genética , República da Coreia , Verduras , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-33279777

RESUMO

BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer (EPIC) cohort. METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5,738 cancer-free EPIC participants with metabolomics data. Partial least squares regression was used to derive fatty acid and endogenous metabolite signatures of WCRF/AICR score in this group. In an independent set of 1,608 colorectal cancer cases and matched controls, odds ratios (OR) and 95% confidence intervals (CI) were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of elevated odd-chain fatty acids, serine, glycine and specific phosphatidylcholines. Signatures were more strongly inversely associated with colorectal cancer risk (fatty acids: OR 0.51 per unit increase, 95% CI 0.29-0.90; endogenous metabolites: OR 0.62 per unit change, 95% CI 0.50-0.78) than the WCRF/AICR score (OR 0.93 per unit change, 95% CI 0.86-1.00) overall. Signature associations were stronger in male compared to female participants. CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33008875

RESUMO

BACKGROUND: Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity-endometrial cancer link in postmenopausal women. METHODS: We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis. RESULTS: The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5-<25 kg/m2 was 2.51 (95% confidence interval, 1.26-5.02). The ORsNIE were 1.95 (1.01-3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06-1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71-1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88-1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89-1.67) through estrogens beyond preceding biomarkers (21% PM). The ORNDE not through biomarkers was 1.29 (0.54-3.09). Waist circumference gave similar results. CONCLUSIONS: Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight. IMPACT: If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.

9.
Int J Cancer ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038275

RESUMO

Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.

10.
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.

11.
Sci Rep ; 10(1): 13814, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796953

RESUMO

Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case-control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.

12.
Int J Cancer ; 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32734650

RESUMO

Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed for N1-acetylspermidine, isatin, p-hydroxyphenyllactic acid, tyrosine, sphingosine, l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, γ-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.

13.
Crit Rev Oncol Hematol ; 154: 103066, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32853883

RESUMO

The growing insights in the next-generation immunotherapy and the state-of-the-art advancement in targeted-agents significantly improved clinical outcome of cancer patients by pointing towards a unexplored Achilles' heel. Novel toxicity profiles have been uncovered, representing unmet medical needs. Thus, a panel of expert provide comprehensive pharmacological and clinical evidence, to provide a patient-tailored approach to metabolic adverse events associated with novel anti-cancer treatments. Prompted by the need of a multidisciplinary cooperation, a working group of Associazione Italiana Oncologia Medica (AIOM), Associazione Medici Diabetologi (AMD) and Società Italiana Farmacologia (SIF) examined the available literature data. The identification of patient risk profile and the characterization of metabolic effects of novel anti-tumour drugs is clearly a clinical challenge that can be addressed by a multidisciplinary clinical approach. Therefore, this review pinpoints the relevance of the challenging profiling of the patient suffering from dysmetabolic conditions induced by the novel therapeutics in medical oncology.


Assuntos
Neoplasias/tratamento farmacológico , Médicos , Consenso , Humanos , Fatores Imunológicos , Itália , Oncologia
14.
Cancer Epidemiol Biomarkers Prev ; 29(9): 1739-1749, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32616494

RESUMO

BACKGROUND: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case-control analysis. RESULTS: A positive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintileQ5-Q1 = 1.29; 95% confidence interval (CI) = 1.03-1.62; P trend = 0.02, q-value = 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 = 1.10; 95% CI = 1.01-1.21; P trend = 0.03) and n-3 α-linolenic acid (HRQ5-Q1 = 1.18; 95% CI = 1.05-1.34; P trend = 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertileT3-T1 = 1.39; 95% CI = 0.99-1.94; P trend = 0.06) and α-linolenic acids (ORT3-T1 = 1.30; 95% CI = 0.98-1.72; P trend = 0.06). CONCLUSIONS: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and α-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer. IMPACT: If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk.

15.
Am J Clin Nutr ; 112(3): 631-643, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619242

RESUMO

BACKGROUND: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. OBJECTIVES: The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. METHODS: This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. RESULTS: After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) ≥25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI <25 [HR: 1.09 (95% CI: 0.98, 1.22) per 50 g/d) (P-interaction = 0.022). The GL-CHD association did not differ between men [HR: 1.19 (95% CI: 1.08, 1.30) per 50 g/d] and women [HR: 1.22 (95% CI: 1.07, 1.40) per 50 g/d] (test for interaction not significant). GI was associated with CHD risk only in the continuous model [HR: 1.04 (95% CI: 1.00, 1.08) per 5 units/d]. High available carbohydrate was associated with greater CHD risk [HR: 1.11 (95% CI: 1.03, 1.18) per 50 g/d]. High sugar intake was associated with greater CHD risk [HR: 1.09 (95% CI: 1.02, 1.17) per 50 g/d]. CONCLUSIONS: This large pan-European study provides robust additional support for the hypothesis that a diet that induces a high glucose response is associated with greater CHD risk.


Assuntos
Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Índice Glicêmico , Carga Glicêmica , Adulto , Idoso , Estudos de Coortes , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco
16.
Food Chem ; 330: 127317, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32569934

RESUMO

Fermentation may enhance the nutritional properties of foods by increasing metabolite bioactivity or bioavailability. This study explored the effect of fermentation on isoflavone bioavailability and metabolism. Isoflavone metabolites were tracked in foods and biospecimens of healthy adults after fermented soybean (FS) or non-fermented soybean (NFS) consumption in a randomized, controlled, crossover intervention study. The change in soybean isoflavones caused by fermentation resulted in faster absorption and higher bioavailability after consumption of FS. Although the urinary level of total isoflavone metabolites was similar after the consumption of the two diets, urinary genistein 7-O-sulfate was derived as a discriminant metabolite for the FS diet by partial least squares discriminant analysis. This study suggests that an isoflavone conjugate profile might be a more appropriate marker than total isoflavone levels for discriminating between the consumption of FS and NFS diets.


Assuntos
Análise de Alimentos/métodos , Isoflavonas/análise , Isoflavonas/farmacocinética , Soja/metabolismo , Adulto , Disponibilidade Biológica , Dieta , Feminino , Alimentos e Bebidas Fermentados , Genisteína/metabolismo , Humanos , Isoflavonas/sangue , Isoflavonas/urina , Masculino , Pessoa de Meia-Idade
17.
Scand J Med Sci Sports ; 30(9): 1675-1684, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32350931

RESUMO

OBJECTIVE: The aim was to evaluate the effect of a home-based exercise program on functional capacity, health-related quality of life (HRQoL), and disability, in patients with systemic sclerosis (SSc). METHODS: A 6-month randomized controlled trial was conducted on SSc patients by comparing a home-based minimally supervised exercise program (exercise on a stationary cycle and strengthening of upper limbs; stretching of the hands) with usual care. At baseline and after 3 and 6 months, the patients underwent: 6 minutes walking test; hand mobility in scleroderma test; maximal exercise test on an ergocycle; strength measures (handgrip, quadriceps, and biceps). HRQoL (short-form 36 [SF-36]) and disability (health assessment questionnaire disability index [HAQ-DI]) were measured at the same time. RESULTS: Forty-four patients participated in the study. Twenty-two were randomly assigned to the intervention group (IG, mean age 63.60 ± 10.40 years) and 22 to the control group (CG, 61.80 ± 14.40 years). At 6 months, the distance walked in 6 minutes increased by 46 m (baseline 486, 95% CI 458-513 m; 6 months 532, 95% CI 504-561 m) in IG, whereas it decreased by 5 m (baseline 464, 95% CI 431-497 m; 6 months 459, 95% CI 427-490 m) in CG with a significantly different temporal trend at the between-groups comparison (P < .001). An improvement was also observed for strength measures (handgrip, P = .003; quadriceps, P < .001; biceps, P < .001), for the SF-36 physical component score (P < .001) and for the HAQ-DI (P = .011). CONCLUSIONS: This study indicates that in SSc patients, a minimally supervised home-based exercise program improves physical performance, quality of life, and disability in comparison with usual care.

18.
Mov Disord ; 35(7): 1258-1263, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32357270

RESUMO

BACKGROUND: Parkinson's disease (PD) etiology is not well understood. Reported inverse associations with smoking and coffee consumption prompted the investigation of alcohol consumption as a risk factor, for which evidence is inconclusive. OBJECTIVE: To assess the associations between alcohol consumption and PD risk. METHODS: Within NeuroEPIC4PD, a prospective European population-based cohort, 694 incident PD cases were ascertained from 209,998 PD-free participants. Average alcohol consumption at different time points was self-reported at recruitment. Cox regression hazard ratios were estimated for alcohol consumption and PD occurrence. RESULTS: No associations between baseline or lifetime total alcohol consumption and PD risk were observed. Men with moderate lifetime consumption (5-29.9 g/day) were at ~50% higher risk compared with light consumption (0.1-4.9 g/day), but no linear exposure-response trend was observed. Analyses by beverage type also revealed no associations with PD. CONCLUSION: Our data reinforce previous findings from prospective studies showing no association between alcohol consumption and PD risk. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

19.
Int J Cancer ; 147(6): 1649-1656, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32176325

RESUMO

Limited evidence exists on the role of modifiable lifestyle factors on the risk of lymphoma. In this work, the associations between adherence to healthy lifestyles and risks of Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a large-scale European prospective cohort. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 2,999 incident lymphoma cases (132 HL and 2,746 NHL) were diagnosed among 453,808 participants after 15 years (median) of follow-up. The healthy lifestyle index (HLI) score combined information on smoking, alcohol intake, diet, physical activity and BMI, with large values of HLI expressing adherence to healthy behavior. Cox proportional hazards models were used to estimate lymphoma hazard ratios (HR) and 95% confidence interval (CI). Sensitivity analyses were conducted by excluding, in turn, each lifestyle factor from the HLI score. The HLI was inversely associated with HL, with HR for a 1-standard deviation (SD) increment in the score equal to 0.78 (95% CI: 0.66, 0.94). Sensitivity analyses showed that the association was mainly driven by smoking and marginally by diet. NHL risk was not associated with the HLI, with HRs for a 1-SD increment equal to 0.99 (0.95, 1.03), with no evidence for heterogeneity in the association across NHL subtypes. In the EPIC study, adherence to healthy lifestyles was not associated with overall lymphoma or NHL risk, while an inverse association was observed for HL, although this was largely attributable to smoking. These findings suggest a limited role of lifestyle factors in the etiology of lymphoma subtypes.

20.
Am J Hum Genet ; 106(3): 389-404, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32109421

RESUMO

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.


Assuntos
Estudo de Associação Genômica Ampla , Leucócitos/ultraestrutura , Nucleotídeos/metabolismo , Telômero , Humanos
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