| 1. |
- Aglago, Elom K., et al.
(författare)
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Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
- 2020
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:3, s. 6-666
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
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| 2. |
- Aglago, Elom K., et al.
(författare)
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Dietary intake and plasma phospholipid concentrations of saturated, monounsaturated and trans fatty acids and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort
- 2021
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 149:4, s. 865-882
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial-processed trans (iTFA), and ruminant-sourced trans (rTFA) fatty acids, and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Baseline fatty acid intakes were estimated in 450 112 participants (6162 developed CRC, median follow-up = 15 years). In a nested case-control study, plasma phospholipid fatty acids were determined by gas chromatography in 433 colon cancer cases and 433 matched controls. Multivariable-adjusted hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were computed using Cox and conditional logistic regression, respectively. Dietary total SFA (highest vs lowest quintile, HRQ5vsQ1 = 0.80; 95%CI:0.69-0.92), myristic acid (HRQ5vsQ1 = 0.83, 95%CI:0.74-0.93) and palmitic acid (HRQ5vsQ1 = 0.81, 95%CI:0.70-0.93) were inversely associated with CRC risk. Plasma myristic acid was also inversely associated with colon cancer risk (highest vs lowest quartile, ORQ4vsQ1 = 0.51; 95%CI:0.32-0.83), whereas a borderline positive association was found for plasma stearic acid (ORQ4vsQ1 = 1.63; 95%CI:1.00-2.64). Dietary total MUFA was inversely associated with colon cancer (per 1-SD increment, HR1-SD = 0.92, 95%CI: 0.85-0.98), but not rectal cancer (HR1-SD = 1.04, 95%CI:0.95-1.15, Pheterogeneity = 0.027). Dietary iTFA, and particularly elaidic acid, was positively associated with rectal cancer (HR1-SD = 1.07, 95%CI:1.02-1.13). Our results suggest that total and individual saturated fatty acids and fatty acids of industrial origin may be relevant to the aetiology of CRC. Both dietary and plasma myristic acid levels were inversely associated with colon cancer risk, which warrants further investigation.
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| 3. |
- Assi, Nada, et al.
(författare)
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Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC
- 2018
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 27:5, s. 531-540
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Tidskriftsartikel (refereegranskat)abstract
- Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites.Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk.Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%.Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators.
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| 4. |
- Assi, Nada, et al.
(författare)
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Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort
- 2018
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Ingår i: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 108:1, s. 117-126
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors.Objective: In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Design: Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed.Results: The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM) (OH) C14:1, C16:1, and C22:2, and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively.Conclusions: This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535.
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| 5. |
- Campa, Daniele, et al.
(författare)
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Genetic variability of the fatty acid synthase pathway is not associated with prostate cancer risk in the European Prospective Investigation on Cancer (EPIC)
- 2011
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 47:3, s. 420-427
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Tidskriftsartikel (refereegranskat)abstract
- A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk.
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| 6. |
- Campa, Daniele, et al.
(författare)
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Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk.
- 2009
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 118:3, s. 565-574
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Tidskriftsartikel (refereegranskat)abstract
- Fatty acid synthase (FAS) is the major enzyme of lipogenesis. It catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to produce palmitic acid. Transcription of the FAS gene is controlled synergistically by the transcription factors ChREBP (carbohydrate response element-binding protein), which is induced by glucose, and SREBP-1 (sterol response element-binding protein-1), which is stimulated by insulin through the PI3K/Akt signal transduction pathway. We investigated whether the genetic variability of the genes encoding for ChREBP, SREBP and FAS (respectively, MLXIPL, SREBF1 and FASN) is related to breast cancer risk and body-mass index (BMI) by studying 1,294 breast cancer cases and 2,452 controls from the European Prospective Investigation on Cancer (EPIC). We resequenced the FAS gene and combined information of SNPs found by resequencing and SNPs from public databases. Using a tagging approach and selecting 20 SNPs, we covered all the common genetic variation of these genes. In this study we were not able to find any statistically significant association between the SNPs in the FAS, ChREBP and SREPB-1 genes and an increased risk of breast cancer overall and by subgroups of age, menopausal status, hormone replacement therapy (HRT) use or BMI. On the other hand, we found that two SNPs in FASN were associated with BMI.
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| 7. |
- Campa, Daniele, et al.
(författare)
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The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk
- 2010
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 10, s. 563-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The single nucleotide polymorphism rs7566605, located in the promoter of the INSIG2 gene, has been the subject of a strong scientific effort aimed to elucidate its possible association with body mass index (BMI). The first report showing that rs7566605 could be associated with body fatness was a genome-wide association study (GWAS) which used BMI as the primary phenotype. Many follow-up studies sought to validate the association of rs7566605 with various markers of obesity, with several publications reporting inconsistent findings. BMI is considered to be one of the measures of choice to evaluate body fatness and there is evidence that body fatness is related with an increased risk of breast cancer (BC).METHODS: we tested in a large-scale association study (3,973 women, including 1,269 invasive BC cases and 2,194 controls), nested within the EPIC cohort, the involvement of rs7566605 as predictor of BMI and BC risk.RESULTS AND CONCLUSIONS: In this study we were not able to find any statistically significant association between this SNP and BMI, nor did we find any significant association between the SNP and an increased risk of breast cancer overall and by subgroups of age, or menopausal status.
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| 8. |
- Campa, Daniele, et al.
(författare)
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Variation in genes coding for AMP-activated protein kinase (AMPK) and breast cancer risk in the European Prospective Investigation on Cancer (EPIC).
- 2011
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Ingår i: Breast Cancer Research and Treatment. - : Springer. - 0167-6806 .- 1573-7217. ; 127:3, s. 761-767
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Tidskriftsartikel (refereegranskat)abstract
- AMP-activated protein kinase (AMPK) is an energy sensing/signalling intracellular protein which is activated by an increase in the cellular AMP:ATP ratio after ATP depletion. Once activated, AMPK inhibits fatty acid synthesis and the Akt-mTOR pathway, and activates the p53-p21 axis. All these molecular mechanisms are thought to play a key role in breast carcinogenesis. We investigated the genetic variability of four genes encoding AMPK (PRKAA1, PRKAA2, PRKAB1 and PRKAB2). Using a tagging approach and selecting SNPs we covered all the common genetic variation of these genes. We tested association of tagging SNPs in our four candidate genes with breast cancer (BC) risk in a study of 1340 BC cases and 2536 controls nested into the European Prospective Investigation into Cancer and Nutrition (EPIC). Given the relevance of AMPK on fatty acid synthesis and the importance of body fatness as a BC risk factor, we tested association of SNPs and body-mass index as well. We observed no statistically significant association between the SNPs in the PRKAs genes and BC risk and BMI after correction for multiple testing.
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| 9. |
- Chajes, Veronique, et al.
(författare)
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Ecological-Level Associations Between Highly Processed Food Intakes and Plasma Phospholipid Elaidic Acid Concentrations: Results From a Cross-Sectional Study Within the European Prospective Investigation Into Cancer and Nutrition (EPIC)
- 2011
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Ingår i: Nutrition and Cancer. - : Informa UK Limited. - 1532-7914 .- 0163-5581. ; 63:8, s. 1235-1250
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Tidskriftsartikel (refereegranskat)abstract
- Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.
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| 10. |
- Chajès, Véronique, et al.
(författare)
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Plasma Elaidic Acid Level as Biomarker of Industrial Trans Fatty Acids and Risk of Weight Change: Report from the EPIC Study.
- 2015
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Few epidemiological studies have examined the association between dietary trans fatty acids and weight gain, and the evidence remains inconsistent. The main objective of the study was to investigate the prospective association between biomarker of industrial trans fatty acids and change in weight within the large study European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
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| 11. |
- Chajes, Veronique, et al.
(författare)
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Plasma phospholipid fatty acid concentrations and risk of gastric adenocarcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST)
- 2011
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 94:5, s. 1304-1313
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiologic data suggest that diet is a risk factor in the etiology of gastric cancer. However, the role of dietary fatty acids, a modifiable risk factor, remains relatively unexplored. Objective: The objective of this study was to determine the association of plasma phospholipid fatty acid concentrations, as biomarkers of exogenous and endogenously derived fatty acids, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition-Europe Gastric Cancer (EPIC-EURGAST). Design: Fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 238 cases matched to 626 controls by age, sex, study center, and date of blood donation. Conditional logistic regression models adjusted for Helicobacter pylori infection status, BMI, smoking, physical activity, education, and energy intake were used to estimate relative cancer risks. Results: Positive risk associations for gastric cancer were observed in the highest compared with the lowest quartiles of plasma oleic acid (OR: 1.72; 95% CI: 1.01, 2.94), di-homo-gamma-linolenic acid (OR: 1.92; 95% CI: 1.10, 3.35), alpha-linolenic acid (OR: 3.20; 95% CI: 1.70, 6.06), and the ratio of MUFAs to saturated fatty acids, as an indicator of stearoyl-CoA desaturase-1 enzyme activity (OR: 1.40; 95% CI: 0.81, 2.43). An inverse risk association was observed with the ratio of linoleic to alpha-linolenic acid (OR: 0.37; 95% CI: 0.20, 0.66). Conclusion: These data suggest that a specific prediagnostic plasma phospholipid fatty acid profile, characterized mainly by high concentrations of oleic acid, alpha-linolenic acid, and di-homo-gamma-linolenic acid, which presumably reflect both a complex dietary pattern and altered fatty acid metabolism, may be related to increased gastric cancer risk. Am J Clin Nutr 2011;94:1304-13.
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| 12. |
- Crowe, Francesca L., et al.
(författare)
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Circulating Fatty Acids and Prostate Cancer Risk : Individual Participant Meta-Analysis of Prospective Studies
- 2014
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 106:9, s. dju240-
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Forskningsöversikt (refereegranskat)abstract
- BackgroundIndividual studies have suggested that some circulating fatty acids are associated with prostate cancer risk, but have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.MethodsPrincipal investigators of prospective studies on circulating fatty acids and prostate cancer were invited to collaborate. Investigators provided individual participant data on circulating fatty acids (weight percent) and other characteristics of prostate cancer cases and controls. Prostate cancer risk by study-specific fifths of 14 fatty acids was estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided.ResultsFive thousand and ninety-eight case patients and 6649 control patients from seven studies with an average follow-up of 5.1 (SD = 3.3) years were included. Stearic acid (18: 0) was inversely associated with total prostate cancer (odds ratio [OR] Q5 vs Q1 = 0.88, 95% confidence interval [CI] = 0.78 to 1.00, P-trend = .043). Prostate cancer risk was, respectively, 14% and 16% greater in the highest fifth of eicosapentaenoic acid (20:5n-3) (OR = 1.14, 95% CI = 1.01 to 1.29, P-trend = .001) and docosapentaenoic acid (22: 5n-3) (OR = 1.16, 95% CI = 1.02 to 1.33, P-trend = .003), but in each case there was heterogeneity between studies (P = .022 and P < .001, respectively). There was heterogeneity in the association between docosapentaenoic acid and prostate cancer by grade of disease (P = .006); the association was statistically significant for low-grade disease but not high-grade disease. The remaining 11 fatty acids were not statistically associated with total prostate cancer risk.ConclusionThere was no strong evidence that circulating fatty acids are important predictors of prostate cancer risk. It is not clear whether the modest associations of stearic, eicosapentaenoic, and docosapentaenoic acid are causal.
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| 13. |
- Cust, Anne E., et al.
(författare)
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Metabolic syndrome, plasma lipid, lipoprotein and glucose levels, and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2007
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Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 14:3, s. 755-767
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Tidskriftsartikel (refereegranskat)abstract
- To clarify the role of metabolic factors in endometrial carcinogenesis, we conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), and examined the relation between prediagnostic plasma lipids, lipoproteins, and glucose, the metabolic syndrome (MetS; a cluster of metabolic factors) and endometrial cancer risk. Among pre- and postmenopausal women, 284 women developed endometrial cancer during follow-up. Using risk set sampling, 546 matched control subjects were selected. From conditional logistic regression models, high-density lipoprotein cholesterol (HDL-C) levels were inversely associated with risk body mass index (BMI)-adjusted relative risk (FR) for top versus bottom quartile 0.61 (95% confidence intervals (CI) 0.38-0.97), P-trend= 0.02). Glucose levels were positively associated with risk (BMI-adjusted RR top versus bottom quartile 1.69 (95% Cl 0.99-2.90), P-trend, = 0.03), which appeared stronger among postmenopausal women (BMI-adjusted RR top versus bottom tertile 2.61 (95% Cl 1.46-4.66), P-trend=0.0006, P-heterogeneity=0.13) and never-users of exogenous hormones (P-heterogeneity=0-005 for oral contraceptive (OC) use and 0.05 for hormone replacement therapy-use). The associations of HDL-C and glucose with risk were no longer statistically significant after further adjustment for obesity-related hormones. Plasma total cholesterol, Low-density lipoprotein cholesterol (LDL-C), and triglycerides were not significantly related to overall risk. The presence of MetS was associated with risk (RR 2.12 (95% CI 1.51-2.97)), which increased with the number of MetS factors (P-trend=0.02). An increasing number of MetS factors other than waist circumference, however, was marginally significantly associated with risk only in women with waist circumference above the median (P-interaction=0-01). None of the associations differed significantly by fasting status. These findings suggest that metabolic abnormalities and obesity may act synergistically to increase endometrial cancer risk.
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| 14. |
- Dahm, Christina C., et al.
(författare)
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Fatty acid patterns and risk of prostate cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition
- 2012
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 96:6, s. 1354-1361
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatty acids in blood may be related to the risk of prostate cancer, but epidemiologic evidence is inconsistent. Blood fatty acids are correlated through shared food sources and common endogenous desaturation and elongation pathways. Studies of individual fatty acids cannot take this into account, but pattern analysis can. Treelet transform (TT) is a novel method that uses data correlation structures to derive sparse factors that explain variation. Objective: The objective was to gain further insight in the association between plasma fatty acids and risk of prostate cancer by applying TT to take data correlations into account. Design: We reanalyzed previously published data from a case-control study of prostate cancer nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. TT was used to derive factors explaining the variation in 26 plasma phospholipid fatty acids of 962 incident prostate cancer cases matched to 1061 controls. Multiple imputation was used to deal with missing data in covariates. ORs of prostate cancer according to factor scores were determined by using multivariable conditional logistic regression. Results: Four simple factors explained 38% of the variation in plasma fatty acids. A high score on a factor reflecting a long-chain n-3 PUFA pattern was associated with greater risk of prostate cancer (OR for highest compared with lowest quintile: 1.36; 95% CI: 0.99, 1.86; P-trend = 0.041). Conclusion: Pattern analyses using TT groupings of correlated fatty acids indicate that intake or metabolism of long-chain n-3 PUFAs may be relevant to prostate cancer etiology. Am J Clin Nutr 2012;96:1354-61.
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| 15. |
- Dossus, Laure, et al.
(författare)
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Reproductive risk factors and endometrial cancer : the European prospective investigation into cancer and nutrition
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:2, s. 442-451
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Tidskriftsartikel (refereegranskat)abstract
- Endometrial cancer risk has been associated with reproductive factors (age at menarche, age at menopause, parity, age at first and last birth, time since last birth and use of oral contraceptives (OCs)]. However, these factors are closely interrelated and whether they act independently still requires clarification. We conducted a study to examine the association of menstrual and reproductive variables with the risk of endometrial cancer among the European Prospective Investigation into Cancer and Nutrition (EPIC). Among the 302,618 women eligible for the study, 1,017 incident endometrial cancer cases were identified. A reduction in endometrial cancer risk was observed in women with late menarche, early menopause, past OC use, high parity and a shorter time since last full-term pregnancy (FTP). No association was observed for duration of breast feeding after adjustment for number of FTP or for abortion (spontaneous or induced). After mutual adjustment, late age at menarche, early age at menopause and duration of OC use showed similar risk reductions of 7-8% per year of menstrual life, whereas the decreased risk associated with cumulative duration of FTPs was stronger (22% per year). In conclusion, our findings confirmed a reduction in risk of endometrial cancer with factors associated with a lower cumulative exposure to estrogen and/or higher exposure to progesterone, such as increasing number of FTPs and shorter menstrual lifespan and, therefore, support an important role of hormonal mechanisms in endometrial carcinogenesis.
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| 16. |
- Emaus, Marleen J., et al.
(författare)
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Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:12, s. 2887-2899
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Tidskriftsartikel (refereegranskat)abstract
- Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3: 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3: 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.
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| 17. |
- Freisling, Heinz, et al.
(författare)
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Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study
- 2018
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 57:7, s. 2399-2408
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 Springer-Verlag GmbH Germany Purpose: There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years. Methods: This study includes 373,293 men and women, 25–70 years old, recruited between 1992 and 2000 from 10 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Habitual intake of nuts including peanuts, together defined as nut intake, was estimated from country-specific validated dietary questionnaires. Body weight was measured at recruitment and self-reported 5 years later. The association between nut intake and body weight change was estimated using multilevel mixed linear regression models with center/country as random effect and nut intake and relevant confounders as fixed effects. The relative risk (RR) of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to baseline body mass index (BMI). Results: On average, study participants gained 2.1 kg (SD 5.0 kg) over 5 years. Compared to non-consumers, subjects in the highest quartile of nut intake had less weight gain over 5 years (−0.07 kg; 95% CI −0.12 to −0.02) (P trend = 0.025) and had 5% lower risk of becoming overweight (RR 0.95; 95% CI 0.92–0.98) or obese (RR 0.95; 95% CI 0.90–0.99) (both P trend < 0.008). Conclusions: Higher intake of nuts is associated with reduced weight gain and a lower risk of becoming overweight or obese.
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| 18. |
- Gasull, Magda, et al.
(författare)
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Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort
- 2019
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 169, s. 417-433
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.
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| 19. |
- Harewood, Rhea, et al.
(författare)
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Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk : a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2024
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Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 101
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Tidskriftsartikel (refereegranskat)abstract
- Background: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain.Methods: In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk.Findings: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47–0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59–0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer.Interpretation: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. Funding: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).
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| 20. |
- Hoeft, Birgit, et al.
(författare)
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Polymorphisms in fatty acid metabolism-related genes are associated with colorectal cancer risk
- 2010
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 31:3, s. 466-472
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is the third most common malignant tumor and the fourth leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in-depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. Three hundred and ninety two single-nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of > 5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), phospholipase A2 group VI (PLA2G6) and transient receptor potential vanilloid 3 were associated with higher risk for CRC, whereas prostaglandin E receptor 2 (PTGER2) was associated with lower CRC risk. A significant inverse association (P < 0.006) was found for PTGER2 GGG haplotype, whereas HPGD AGGAG and PLA2G3 CT haplotypes were significantly (P < 0.001 and P = 0.003, respectively) associated with higher risk of CRC. Based on these data, we present for the first time the association of HPGD variants with CRC risk. Our results support the key role of prostanoid signaling in colon carcinogenesis and suggest a relevance of genetic variation in fatty acid metabolism-related genes and CRC risk.
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| 21. |
- Huybrechts, Inge, et al.
(författare)
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Characterization of the degree of food processing in the European prospective investigation into cancer and nutrition : application of the nova classification and validation using selected biomarkers of food processing
- 2022
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Ingår i: Frontiers in Nutrition. - : Frontiers Media S.A.. - 2296-861X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidemiological studies have demonstrated an association between the degree of food processing in our diet and the risk of various chronic diseases. Much of this evidence is based on the international Nova classification system, which classifies food into four groups based on the type of processing: (1) Unprocessed and minimally processed foods, (2) Processed culinary ingredients, (3) Processed foods, and (4) “Ultra-processed” foods (UPF). The ability of the Nova classification to accurately characterise the degree of food processing across consumption patterns in various European populations has not been investigated so far. Therefore, we applied the Nova coding to data from the European Prospective Investigation into Cancer and Nutrition (EPIC) in order to characterize the degree of food processing in our diet across European populations with diverse cultural and socio-economic backgrounds and to validate this Nova classification through comparison with objective biomarker measurements.Methods: After grouping foods in the EPIC dataset according to the Nova classification, a total of 476,768 participants in the EPIC cohort (71.5% women; mean age 51 [standard deviation (SD) 9.93]; median age 52 [percentile (p)25–p75: 58–66] years) were included in the cross-sectional analysis that characterised consumption patterns based on the Nova classification. The consumption of food products classified as different Nova categories were compared to relevant circulating biomarkers denoting food processing, measured in various subsamples (N between 417 and 9,460) within the EPIC cohort via (partial) correlation analyses (unadjusted and adjusted by sex, age, BMI and country). These biomarkers included an industrial transfatty acid (ITFA) isomer (elaidic acid; exogenous fatty acid generated during oil hydrogenation and heating) and urinary 4-methyl syringol sulfate (an indicator for the consumption of smoked food and a component of liquid smoke used in UPF).Results: Contributions of UPF intake to the overall diet in % grams/day varied across countries from 7% (France) to 23% (Norway) and their contributions to overall % energy intake from 16% (Spain and Italy) to >45% (in the UK and Norway). Differences were also found between sociodemographic groups; participants in the highest fourth of UPF consumption tended to be younger, taller, less educated, current smokers, more physically active, have a higher reported intake of energy and lower reported intake of alcohol. The UPF pattern as defined based on the Nova classification (group 4;% kcal/day) was positively associated with blood levels of industrial elaidic acid (r = 0.54) and 4-methyl syringol sulfate (r = 0.43). Associations for the other 3 Nova groups with these food processing biomarkers were either inverse or non-significant (e.g., for unprocessed and minimally processed foods these correlations were –0.07 and –0.37 for elaidic acid and 4-methyl syringol sulfate, respectively).Conclusion: These results, based on a large pan-European cohort, demonstrate sociodemographic and geographical differences in the consumption of UPF. Furthermore, these results suggest that the Nova classification can accurately capture consumption of UPF, reflected by stronger correlations with circulating levels of industrial elaidic acid and a syringol metabolite compared to diets high in minimally processed foods.
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| 22. |
- Imamura, Fumiaki, et al.
(författare)
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A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes : The EPIC-InterAct case-cohort study
- 2017
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Ingår i: PLoS Medicine. - : Public Library Science. - 1549-1277 .- 1549-1676. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Background Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated.Methods and findings We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested casecohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of.-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding.Conclusions A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.
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| 23. |
- Jakobsen, Marianne U., et al.
(författare)
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Fish consumption and subsequent change in body weight in European women and men
- 2013
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Ingår i: British Journal of Nutrition. - 1475-2662 .- 0007-1145. ; 109:2, s. 353-362
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Tidskriftsartikel (refereegranskat)abstract
- Fish consumption is the major dietary source of EPA and DHA, which according to rodent experiments may reduce body fat mass and prevent obesity. Only a few human studies have investigated the association between fish consumption and body-weight gain. We investigated the association between fish consumption and subsequent change in body weight. Women and men (n 344 757) participating in the European Prospective Investigation into Cancer and Nutrition were followed for a median of 5.0 years. Linear and logistic regression were used to investigate the associations between fish consumption and subsequent change in body weight. Among women, the annual weight change was 5.70 (95% CI 4.35, 7.06), 2.23 (95% CI 0.16, 4.31) and 11.12 (95% CI 8.17, 14.08) g/10 g higher total, lean and fatty fish consumption per d, respectively. The OR of becoming overweight in 5 years among women who were normal weight at enrolment was 1.02 (95% CI 1.01, 1.02), 1.01 (95% CI 1.00, 1.02) and 1.02 (95% CI 1.01, 1.04) g/10 g higher total, lean and fatty consumption per d, respectively. Among men, fish consumption was not statistically significantly associated with weight change. Adjustment for potential over-or underestimation of fish consumption did not systematically change the observed associations, but the 95% CI became wider. The results in subgroups from analyses stratified by age or BMI at enrolment were not systematically different. In conclusion, the present study suggests that fish consumption has no appreciable association with body-weight gain.
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| 24. |
- Jakobsen, Marianne U., et al.
(författare)
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Plasma Phospholipid Long-Chain n-3 Polyunsaturated Fatty Acids and Body Weight Change
- 2011
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Ingår i: Obesity Facts. - : S. Karger AG. - 1662-4033 .- 1662-4025. ; 4:4, s. 312-318
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We investigated the association between the proportion of long-chain n-3 polyunsaturated fatty acids (PUFA) in plasma phospholipids from blood samples drawn at enrollment and subsequent change in body weight. Sex, age, and BMI were considered as potential effect modifiers. Method: A total of 1,998 women and men participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) were followed for a median of 4.9 years. The associations between the proportion of plasma phospholipid long-chain n-3 PUFA and change in weight were investigated using mixed-effect linear regression. Results: The proportion of long-chain n-3 PUFA was not associated with change in weight. Among all participants, the 1-year weight change was -0.7 g per 1% point higher long-chain n-3 PUFA level (95% confidence interval: -20.7 to 19.3). The results when stratified by sex, age, or BMI groups were not systematically different. Conclusion: The results of this study suggest that the proportion of long-chain n-3 PUFA in plasma phospholipids is not associated with subsequent change in body weight within the range of exposure in the general population.
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| 25. |
- Kaaks, Rudolf, et al.
(författare)
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Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status-Results from the EPIC cohort
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 134:8, s. 1947-1957
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Tidskriftsartikel (refereegranskat)abstract
- Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1=1.56 (95% CI 1.15-2.13), p(trend)=0.02 for testosterone and ORQ4-Q1=1.33 (95% CI 0.99-1.79), p(trend)=0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1=1.32 (95% CI 0.87-2.01), p(trend)=0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1=0.94 (95% CI 0.60-1.47), p(trend)=0.34, p(het)=0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.
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