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1.
  • Aglago, Elom K., et al. (författare)
  • Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study
  • 2023
  • Ingår i: British Journal of Cancer. - : Springer Nature. - 0007-0920 .- 1532-1827. ; 128, s. 1529-1540
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Iron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.Methods: We examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.Results: Of 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99).Conclusions: Our findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.
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2.
  • Almanza-Aguilera, Enrique, et al. (författare)
  • Intake of the total, classes, and subclasses of (poly)phenols and risk of prostate cancer : a prospective analysis of the EPIC study
  • 2023
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Existing epidemiological evidence regarding the potential role of (poly)phenol intake in prostate cancer (PCa) risk is scarce and, in the case of flavonoids, it has been suggested that their intake may increase PCa risk. We investigated the associations between the intake of the total and individual classes and subclasses of (poly)phenols and the risk of PCa, including clinically relevant subtypes. The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort included 131,425 adult men from seven European countries. (Poly)phenol intake at baseline was assessed by combining validated center/country-specific dietary questionnaires and the Phenol-Explorer database. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). In total, 6939 incident PCa cases (including 3501 low-grade and 710 high-grade, 2446 localized and 1268 advanced, and 914 fatal Pca cases) were identified during a mean follow-up of 14 years. No associations were observed between the total intake of (poly)phenols and the risk of PCa, either overall (HRlog2 = 0.99, 95% CI 0.94–1.04) or according to PCa subtype. Null associations were also found between all classes (phenolic acids, flavonoids, lignans, and stilbenes) and subclasses of (poly)phenol intake and the risk of PCa, overall and according to PCa subtype. The results of the current large prospective cohort study do not support any association between (poly)phenol intake and PCa incidence.
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3.
  • Cervenka, Iris, et al. (författare)
  • Exogenous hormone use and cutaneous melanoma risk in women : The European Prospective Investigation into Cancer and Nutrition
  • 2020
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 146:12, s. 3267-3280
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.
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4.
  • Cheng, Tuck Seng, et al. (författare)
  • Circulating free insulin-like growth factor-I and prostate cancer : a case-control study nested in the European prospective investigation into cancer and nutrition
  • 2024
  • Ingår i: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 24:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk.METHODS: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics.RESULTS: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade.CONCLUSIONS: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.
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5.
  • Christakoudi, Sofia, et al. (författare)
  • Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition
  • 2020
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:10, s. 2680-2693
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.
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7.
  • Dam, Veerle, et al. (författare)
  • Association of menopausal characteristics and risk of coronary heart disease : A pan-European case-cohort analysis
  • 2019
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:4, s. 1275-1285
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors.Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders.Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors.Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease.
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8.
  • Deschasaux, Melanie, et al. (författare)
  • Association between nutritional profiles of foods underlying Nutri-Score front-of-pack labels and mortality : EPIC cohort study in 10 European countries
  • 2020
  • Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 370
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. DESIGN Population based cohort study. SETTING European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from 23 centres in 10 European countries. PARTICIPANTS 521 324 adults; at recruitment, country specific and validated dietary questionnaires were used to assess their usual dietary intakes. A FSAm-NPS score was calculated for each food item per 100 g content of energy, sugars, saturated fatty acids, sodium, fibre, and protein, and of fruit, vegetables, legumes, and nuts. The FSAm-NPS dietary index was calculated for each participant as an energy weighted mean of the FSAm-NPS score of all foods consumed. The higher the score the lower the overall nutritional quality of the diet. MAIN OUTCOME MEASURE Associations between the FSAm-NPS dietary index score and mortality, assessed using multivariable adjusted Cox proportional hazards regression models. RESULTS After exclusions, 501 594 adults (median follow-up 17.2 years, 8 162 730 person years) were included in the analyses. Those with a higher FSAm-NPS dietary index score (highest versus lowest fifth) showed an increased risk of all cause mortality (n=53 112 events from non-external causes; hazard ratio 1.07, 95% confidence interval 1.03 to 1.10, P(0.001 for trend) and mortality from cancer (1.08, 1.03 to 1.13, P(0.001 for trend) and diseases of the circulatory (1.04, 0.98 to 1.11, P=0.06 for trend), respiratory (1.39, 1.22 to 1.59, P(0.001), and digestive (1.22, 1.02 to 1.45, P=0.03 for trend) systems. The age standardised absolute rates for all cause mortality per 10 000 persons over 10 years were 760 (men=1237; women=563) for those in the highest fifth of the FSAm-NPS dietary index score and 661 (men=1008; women=518) for those in the lowest fifth. CONCLUSIONS In this large multinational European cohort, consuming foods with a higher FSAm-NPS score (lower nutritional quality) was associated with a higher mortality for all causes and for cancer and diseases of the circulatory, respiratory, and digestive systems, supporting the relevance of FSAm-NPS to characterise healthier food choices in the context of public health policies (eg, the Nutri-Score) for European populations. This is important considering ongoing discussions about the potential implementation of a unique nutrition labelling system at the European Union level.
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9.
  • Dimou, Niki, et al. (författare)
  • Cigarette Smoking and Endometrial Cancer Risk : observational and Mendelian Randomization Analyses
  • 2022
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 31:9, s. 1839-1848
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Current epidemiologic evidence indicates that smoking is associated with a lower endometrial cancer risk. However, it is unknown if this association is causal or confounded. To further elucidate the role of smoking in endometrial cancer risk, we conducted complementary observational and Mendelian randomization (MR) analyses.METHODS: The observational analyses included 286,415 participants enrolled in the European Prospective Investigation into Cancer and Nutrition and 179,271 participants in the UK Biobank, and multivariable Cox proportional hazards models were used. In two-sample MR analyses, genetic variants robustly associated with lifetime amount of smoking (n = 126 variants) and ever having smoked regularly (n = 112 variants) were selected and their association with endometrial cancer risk (12,906 cancer/108,979 controls from the Endometrial Cancer Association Consortium) was examined.RESULTS: In the observational analysis, lifetime amount of smoking and ever having smoked regularly were associated with a lower endometrial cancer risk. In the MR analysis accounting for body mass index, a genetic predisposition to a higher lifetime amount of smoking was not associated with endometrial cancer risk (OR per 1-SD increment: 1.15; 95% confidence interval: 0.91-1.44). Genetic predisposition to ever having smoked regularly was not associated with risk of endometrial cancer.CONCLUSIONS: Smoking was inversely associated with endometrial cancer in the observational analyses, although unsupported by the MR. Additional studies are required to better understand the possible confounders and mechanisms underlying the observed associations between smoking and endometrial cancer. IMPACT: The results from this analysis indicate that smoking is unlikely to be causally linked with endometrial cancer risk.
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10.
  • Dimou, Niki, et al. (författare)
  • Circulating levels of testosterone, sex hormone binding globulin and colorectal cancer risk: Observational and mendelian randomization analyses
  • 2021
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : AACR Publications. - 1055-9965 .- 1538-7755. ; 30:7, s. 1336-1348
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiologic studies evaluating associations between sex steroid hormones and colorectal cancer risk have yielded inconsistent results. To elucidate the role of circulating levels of testosterone, and sex hormone-binding globulin (SHBG) in colorectal cancer risk, we conducted observational and Mendelian randomization (MR) analyses.Methods: The observational analyses included 333,530 participants enrolled in the UK Biobank with testosterone and SHBG measured. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models. For MR analyses, genetic variants robustly associated with hormone levels were identified and their association with colorectal cancer (42,866 cases/42,752 controls) was examined using two-sample MR.Results: In the observational analysis, there was little evidence that circulating levels of total testosterone were associated with colorectal cancer risk; the MR analyses showed a greater risk for women (OR per 1-SD = 1.09; 95% CI, 1.01-1.17), although pleiotropy may have biased this result. Higher SHBG concentrations were associated with greater colorectal cancer risk for women (HR per 1-SD = 1.16; 95% CI, 1.05-1.29), but was unsupported by the MR analysis. There was little evidence of associations between free testosterone and colorectal cancer in observational andMRanalyses.Conclusions: Circulating concentrations of sex hormones are unlikely to be causally associated with colorectal cancer. Additional experimental studies are required to better understand the possible role of androgens in colorectal cancer development.
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11.
  • Fedirko, Veronika, et al. (författare)
  • Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
  • 2019
  • Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor beta (TGF beta) signaling was associated with CRC risk (P <= 0.001), with most statistically significant genes being SMAD7 (P-BH = 0.008) and SMAD3 (P-BH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.
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12.
  • Feng, Xiaoshuang, et al. (författare)
  • Lung cancer risk discrimination of prediagnostic proteomics measurements compared with existing prediction tools
  • 2023
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 115:9, s. 1050-1059
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test.METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided.RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model.CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.
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13.
  • Gentiluomo, Manuel, et al. (författare)
  • Mitochondrial DNA Copy-Number Variation and Pancreatic Cancer Risk in the Prospective EPIC Cohort
  • 2020
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Philadelphia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 29:3, s. 681-686
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mitochondrial DNA (mtDNA) copy number in peripheral blood has been found to be sociated with risk of developing several cancers. However, data on pancreatic ductal adenocarcinoma DAC) are very limited.Methods: To further our knowledge on this topic, we measured relative mtDNA copy number by a antitative real-time PCR assay in peripheral leukocyte samples of 476PDACcases and 357 controls sted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Results: We observed lower mtDNA copy number with advancing age (P = 6.54 x 10(-5)) and with a high dy mass index (BMI) level (P = 0.004) and no association with sex, smoking behavior, and alcohol nsumption. We found an association between increased mtDNA copy number and decreased risk of veloping PDAC with an odds ratios (OR) of 0.35 [95% confidence interval (CI), 0.160.79; P = 0.01] when mparing the fifth quintile with the first using an unconditional logistic regression and an OR of 0.19 5% CI, 0.07-0.52; P = 0.001) with a conditional analysis. Analyses stratified by BMI showed an sociation between high mtDNA copy number and decreased risk in the stratum of normal weight, nsistent with the main analyses.Conclusions: Our results suggest a protective effect of a higher number of mitochondria, measured in ripheral blood leukocytes, on PDAC risk.Impact: Our findings highlight the importance of understanding the mitochondrial biology in pancreatic ncer.
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14.
  • Gibbs, David Corley, et al. (författare)
  • Association of prediagnostic vitamin D status with mortality among colorectal cancer patients differs by common, inherited vitamin D‐binding protein isoforms
  • 2020
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 147:10, s. 2725-2734
  • Tidskriftsartikel (refereegranskat)abstract
    • Lower prediagnostic circulating 25‐hydroxyvitamin D (25[OH]D)—considered the best marker of total vitamin D exposure—is associated with higher mortality risk among colorectal cancer (CRC) patients. However, it is unknown whether this association differs by the vitamin D‐binding protein (GC) isoform Gc2 (encoded by GC rs4588*C>A, Thr436Lys), which may substantially affect vitamin D metabolism and modify associations of 25(OH)D with colorectal neoplasm risk. Prediagnostic 25(OH)D‐mortality associations according to Gc2 isoform were estimated using multivariable Cox proportional hazards regression among 1281 CRC cases (635 deaths, 483 from CRC) from two large prospective cohorts conducted in the United States (Cancer Prevention Study‐II) and Europe (European Prospective Investigation into Cancer and Nutrition). 25(OH)D measurements were calibrated to a single assay, season standardized, and categorized using Institute of Medicine recommendations (deficient [<30], insufficient [30 ‐ <50], sufficient [≥50 nmol/L]). In the pooled analysis, multivariable‐adjusted hazard ratios (HRs) for CRC‐specific mortality associated with deficient relative to sufficient 25(OH)D concentrations were 2.24 (95% CI 1.44‐3.49) among cases with the Gc2 isoform, and 0.94 (95% CI 0.68‐1.22) among cases without Gc2 (P interaction = .0002). The corresponding HRs for all‐cause mortality were 1.80 (95% CI 1.24‐2.60) among those with Gc2, and 1.12 (95% CI 0.84‐1.51) among those without Gc2 (P interaction = .004). Our findings suggest that the association of prediagnostic vitamin D status with mortality among CRC patients may differ by functional GC isoforms, and patients who inherit the Gc2 isoform (GC rs4588*A) may particularly benefit from higher circulating 25(OH)D for improved CRC prognosis.
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15.
  • Gil-Lespinard, Mercedes, et al. (författare)
  • Plasma concentration of 36 (poly)phenols and prospective body weight change in participants from the EPIC cohort
  • 2024
  • Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 80:2, s. 87-100
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Dietary intake of (poly)phenols has been linked to reduced adiposity and body weight (BW) in several epidemiological studies. However, epidemiological evidence on (poly)phenol biomarkers, particularly plasma concentrations, is scarce. We aimed to investigate the associations between plasma (poly)phenols and prospective BW change in participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Methods: This study included 761 participants with data on BW at baseline and after 5 years of follow-up. Plasma concentrations of 36 (poly)phenols were measured at baseline using liquid chromatography-tandem mass spectrometry. Associations were assessed through general linear mixed models and multinomial logistic regression models, using change in BW as a continuous or as a categorical variable (BW loss, maintenance, gain), respectively. Plasma (poly)phenols were assessed as log2-transformed continuous variables. The false discovery rate (FDR) was used to control for multiple comparisons.Results: Doubling plasma (poly)phenol concentrations showed a borderline trend towards a positive association with BW loss. Plasma vanillic acid showed the strongest association (−0.53 kg/5 years; 95% confidence interval [CI]: −0.99, −0.07). Similar results were observed for plasma naringenin comparing BW loss versus BW maintenance (odds ratio: 1.1; 95% CI: 1.0, 1.2). These results did not remain significant after FDR correction.Conclusion: Higher concentrations of plasma (poly)phenols suggested a tendency towards 5-year BW maintenance or loss. While certain associations seemed promising, they did not withstand FDR correction, indicating the need for caution in interpreting these results. Further studies using (poly) phenol biomarkers are needed to confirm these suggestive protective trends.
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16.
  • His, Mathilde, et al. (författare)
  • Lifestyle correlates of eight breast cancer-related metabolites : a cross-sectional study within the EPIC cohort
  • 2021
  • Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2).Methods: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786).Results: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed.Conclusions: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated.
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17.
  • Hughes, David J., et al. (författare)
  • Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study
  • 2023
  • Ingår i: Free Radical Biology & Medicine. - : Elsevier. - 0891-5849 .- 1873-4596. ; 209, s. 381-393
  • Tidskriftsartikel (refereegranskat)abstract
    • Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30–0.98, Ptrend = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.
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18.
  • Jannasch, Franziska, et al. (författare)
  • Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations
  • 2019
  • Ingår i: The Journal of nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 149:6, s. 1047-1055
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence. OBJECTIVE: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries. METHODS: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association. RESULTS: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea. CONCLUSIONS: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.
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19.
  • Kliemann, Nathalie, et al. (författare)
  • Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2022
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : NLM. - 1055-9965 .- 1538-7755. ; 31:7, s. 1359-1367
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known.METHODS: The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case-control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH; <1st tertile) and metabolically unhealthy (MU; ≥1st tertile) status among the control participants. These metabolic health definitions were combined with normal weight (NW); body mass index (BMI)<25 kg/m2 or waist circumference (WC)<80 cm or waist-to-hip ratio (WHR)<0.8) and overweight (OW; BMI≥25 kg/m2 or WC≥80 cm or WHR≥0.8) status, generating four phenotype groups for each anthropometric measure: (i) MH/NW, (ii) MH/OW, (iii) MU/NW, and (iv) MU/OW.RESULTS: In a multivariable-adjusted conditional logistic regression model, compared with MH/NW individuals, endometrial cancer risk was higher among those classified as MU/NW [ORWC, 1.48; 95% confidence interval (CI), 1.05-2.10 and ORWHR, 1.68; 95% CI, 1.21-2.35] and MU/OW (ORBMI, 2.38; 95% CI, 1.73-3.27; ORWC, 2.69; 95% CI, 1.92-3.77 and ORWHR, 1.83; 95% CI, 1.32-2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (ORWC, 1.94; 95% CI, 1.24-3.04).CONCLUSIONS: Women with metabolic dysfunction appear to have higher risk of endometrial cancer regardless of their body size. However, OW status raises endometrial cancer risk even among women with lower insulin levels, suggesting that obesity-related pathways are relevant for the development of this cancer beyond insulin.IMPACT: Classifying women by metabolic health may be of greater utility in identifying those at higher risk for endometrial cancer than anthropometry per se.
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20.
  • Kohls, Mirjam, et al. (författare)
  • Impact of cumulative body mass index and cardiometabolic diseases on survival among patients with colorectal and breast cancer : a multi-centre cohort study
  • 2022
  • Ingår i: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 22:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Body mass index (BMI) and cardiometabolic comorbidities such as cardiovascular disease and type 2 diabetes have been studied as negative prognostic factors in cancer survival, but possible dependencies in the mechanisms underlying these associations remain largely unexplored. We analysed these associations in colorectal and breast cancer patients.Methods: Based on repeated BMI assessments of cancer-free participants from four European countries in the European Prospective Investigation into Cancer and nutrition (EPIC) study, individual BMI-trajectories reflecting predicted mean BMI between ages 20 to 50 years were estimated using a growth curve model. Participants with incident colorectal or breast cancer after the age of 50 years were included in the survival analysis to study the prognostic effect of mean BMI and cardiometabolic diseases (CMD) prior to cancer. CMD were defined as one or more chronic conditions among stroke, myocardial infarction, and type 2 diabetes. Hazard ratios (HRs) and confidence intervals (CIs) of mean BMI and CMD were derived using multivariable-adjusted Cox proportional hazard regression for mean BMI and CMD separately and both exposures combined, in subgroups of localised and advanced disease.Results: In the total cohort of 159,045 participants, there were 1,045 and 1,620 eligible patients of colorectal and breast cancer. In colorectal cancer patients, a higher BMI (by 1 kg/m2) was associated with a 6% increase in risk of death (95% CI of HR: 1.02–1.10). The HR for CMD was 1.25 (95% CI: 0.97–1.61). The associations for both exposures were stronger in patients with localised colorectal cancer. In breast cancer patients, a higher BMI was associated with a 4% increase in risk of death (95% CI: 1.00–1.08). CMDs were associated with a 46% increase in risk of death (95% CI: 1.01–2.09). The estimates and CIs for BMI remained similar after adjustment for CMD and vice versa.Conclusions: Our results suggest that cumulative exposure to higher BMI during early to mid-adulthood was associated with poorer survival in patients with breast and colorectal cancer, independent of CMD prior to cancer diagnosis. The association between a CMD diagnosis prior to cancer and survival in patients with breast and colorectal cancer was independent of BMI.
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21.
  • Lassale, Camille, et al. (författare)
  • Separate and combined associations of obesity and metabolic health with coronary heart disease : a pan-European case-cohort analysis
  • 2018
  • Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39:5, s. 397-406
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: The hypothesis of 'metabolically healthy obesity' implies that, in the absence of metabolic dysfunction, individuals with excess adiposity are not at greater cardiovascular risk. We tested this hypothesis in a large pan-European prospective study.Methods and results: We conducted a case-cohort analysis in the 520 000-person European Prospective Investigation into Cancer and Nutrition study ('EPIC-CVD'). During a median follow-up of 12.2 years, we recorded 7637 incident coronary heart disease (CHD) cases. Using cut-offs recommended by guidelines, we defined obesity and overweight using body mass index (BMI), and metabolic dysfunction ('unhealthy') as ≥ 3 of elevated blood pressure, hypertriglyceridaemia, low HDL-cholesterol, hyperglycaemia, and elevated waist circumference. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CI) within each country using Prentice-weighted Cox proportional hazard regressions, accounting for age, sex, centre, education, smoking, diet, and physical activity. Compared with metabolically healthy normal weight people (reference), HRs were 2.15 (95% CI: 1.79; 2.57) for unhealthy normal weight, 2.33 (1.97; 2.76) for unhealthy overweight, and 2.54 (2.21; 2.92) for unhealthy obese people. Compared with the reference group, HRs were 1.26 (1.14; 1.40) and 1.28 (1.03; 1.58) for metabolically healthy overweight and obese people, respectively. These results were robust to various sensitivity analyses.Conclusion: Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than their healthy counterparts. Conversely, irrespective of metabolic health, overweight and obese people had higher CHD risk than lean people. These findings challenge the concept of 'metabolically healthy obesity', encouraging population-wide strategies to tackle obesity.
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22.
  • Löding, Sebastian, et al. (författare)
  • Altered plasma metabolite levels can be detected years before a glioma diagnosis
  • 2023
  • Ingår i: JCI Insight. - : American Society For Clinical Investigation. - 2379-3708. ; 8:19
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic and metabolic changes in tissue and blood are reported to occur several years before glioma diagnosis. Since gliomas are currently detected late, a liquid biopsy for early detection could affect the quality of life and prognosis of patients. Here, we present a nested case-control study of 550 prediagnostic glioma cases and 550 healthy controls from the Northern Sweden Health and Disease study (NSHDS) and the European Prospective Investigation into Cancer and Nutrition (EPIC) study. We identified 93 significantly altered metabolites related to glioma development up to 8 years before diagnosis. Out of these metabolites, a panel of 20 selected metabolites showed strong disease correlation and a consistent progression pattern toward diagnosis in both the NSHDS and EPIC cohorts, and they separated future cases from controls independently of biological sex. The blood metabolite panel also successfully separated both lower-grade glioma and glioblastoma cases from controls, up to 8 years before diagnosis in patients within the NSHDS cohort and up to 2 years before diagnosis in EPIC. Pathway enrichment analysis detected metabolites related to the TCA cycle, Warburg effect, gluconeogenesis, and cysteine, pyruvate, and tyrosine metabolism as the most affected.
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23.
  • Mahamat-Saleh, Yahya, et al. (författare)
  • Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)
  • 2023
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 152:3, s. 348-362
  • Tidskriftsartikel (refereegranskat)abstract
    • Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country-specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal-cell carcinoma (BCC): n = 8711; squamous-cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow-up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1-4.9 g/day: HR = 1.44, 95% CI = 1.17-1.77; Ptrend =.001), BCC (HR = 1.12, 95% CI = 1.01-1.23; Ptrend =.04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; Ptrend =.17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; Ptrend =.13; BCC: HR = 1.08, 95% CI = 1.00-1.17, Ptrend =.03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, Ptrend =.13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08-1.99; Ptrend =.0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31; Ptrend =.14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11-1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer.
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24.
  • Mahamat-Saleh, Yahya, et al. (författare)
  • Citrus intake and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)
  • 2020
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 35:11, s. 1057-1067
  • Tidskriftsartikel (refereegranskat)abstract
    • Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose–response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03–1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02–1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04–1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01–1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02–1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose–response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.
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25.
  • Mao, Ziling, et al. (författare)
  • Prediagnostic serum glyceraldehyde-derived advanced glycation end products and mortality among colorectal cancer patients
  • 2023
  • Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 152:11, s. 2257-2268
  • Tidskriftsartikel (refereegranskat)abstract
    • Glyceraldehyde-derived advanced glycation end products (glycer-AGEs) could contribute to colorectal cancer development and progression due to their pro-oxidative and pro-inflammatory properties. However, the association of glycer-AGEs with mortality after colorectal cancer diagnosis has not been previously investigated. Circulating glycer-AGEs were measured by competitive ELISA. Multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for associations of circulating glycer-AGEs concentrations with CRC-specific and all-cause mortality among 1034 colorectal cancer (CRC) cases identified within the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1993 and 2013. During a mean of 48 months of follow-up, 529 participants died (409 from CRC). Glycer-AGEs were statistically significantly positively associated with CRC-specific (HRQ5 vs Q1 = 1.53, 95% CI: 1.04-2.25, Ptrend =.002) and all-cause (HRQ5 vs Q1 = 1.62, 95% CI: 1.16-2.26, Ptrend <.001) mortality among individuals with CRC. There was suggestion of a stronger association between glycer-AGEs and CRC-specific mortality among patients with distal colon cancer (per SD increment: HRproximal colon = 1.02, 95% CI: 0.74-1.42; HRdistal colon = 1.51, 95% CI: 1.20-1.91; Peffect modification =.02). The highest HR was observed among CRC cases in the highest body mass index (BMI) and glycer-AGEs category relative to lowest BMI and glycer-AGEs category for both CRC-specific (HR = 1.78, 95% CI: 1.02-3.01) and all-cause mortality (HR = 2.15, 95% CI: 1.33-3.47), although no statistically significant effect modification was observed. Our study found that prediagnostic circulating glycer-AGEs are positively associated with CRC-specific and all-cause mortality among individuals with CRC. Further investigations in other populations and stratifying by tumor location and BMI are warranted.
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26.
  • Matta, Michèle, et al. (författare)
  • Dietary intake of trans fatty acids and breast cancer risk in 9 European countries
  • 2021
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors. Results: After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06–1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06–1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01–1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03–1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01–1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes. Conclusions: These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations.
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27.
  • Mayén, Ana Lucia, et al. (författare)
  • A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk
  • 2022
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 37:9, s. 915-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk. Objective: Leveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk. Methods: Within the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases. Results: Mean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite. Conclusions: Increasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.
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28.
  • Meyer, Antoine, et al. (författare)
  • Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis
  • 2024
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 59:4, s. 558-568
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Nutri-score is now widely available in food packages in Europe.Aim: To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.Methods: We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake.Results: We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24–3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69–1.21; p-trend: 0.76).Conclusions: A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.
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29.
  • Mori, Nagisa, et al. (författare)
  • Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women : A Prospective Study and Meta-Analysis
  • 2021
  • Ingår i: JNCI cancer spectrum. - : Oxford University Press. - 2515-5091. ; 5:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.Methods: We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone-binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.Results: In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment = 1.17 [95% confidence interval = 1.00 to 1.38]; odds ratioquartile4-quartile1  = 1.33 [95% confidence interval = 0.89 to 1.97], P trend  = .20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk.Conclusion: Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women.
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30.
  • Nimptsch, Katharina, et al. (författare)
  • Prospective and Mendelian randomization analyses on the association of circulating fatty acid binding protein 4 (FABP-4) and risk of colorectal cancer
  • 2023
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Fatty acid binding protein 4 (FABP-4) is a lipid-binding adipokine upregulated in obesity, which may facilitate fatty acid supply for tumor growth and promote insulin resistance and inflammation and may thus play a role in colorectal cancer (CRC) development. We aimed to investigate the association between circulating FABP-4 and CRC and to assess potential causality using a Mendelian randomization (MR) approach.Methods: The association between pre-diagnostic plasma measurements of FABP-4 and CRC risk was investigated in a nested case-control study in 1324 CRC cases and the same number of matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A two-sample Mendelian randomization study was conducted based on three genetic variants (1 cis, 2 trans) associated with circulating FABP-4 identified in a published genome-wide association study (discovery n = 20,436) and data from 58,131 CRC cases and 67,347 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry.Results: In conditional logistic regression models adjusted for potential confounders including body size, the estimated relative risk, RR (95% confidence interval, CI) per one standard deviation, SD (8.9 ng/mL) higher FABP-4 concentration was 1.01 (0.92, 1.12) overall, 0.95 (0.80, 1.13) in men and 1.09 (0.95, 1.25) in women. Genetically determined higher FABP-4 was not associated with colorectal cancer risk (RR per FABP-4 SD was 1.10 (0.95, 1.27) overall, 1.03 (0.84, 1.26) in men and 1.21 (0.98, 1.48) in women). However, in a cis-MR approach, a statistically significant association was observed in women (RR 1.56, 1.09, 2.23) but not overall (RR 1.23, 0.97, 1.57) or in men (0.99, 0.71, 1.37).Conclusions: Taken together, these analyses provide no support for a causal role of circulating FABP-4 in the development of CRC, although the cis-MR provides some evidence for a positive association in women, which may deserve to be investigated further.
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31.
  • Perez-Cornago, Aurora, et al. (författare)
  • Plant foods, dietary fibre and risk of ischaemic heart disease in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
  • 2021
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 50:1, s. 212-222
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological evidence indicates that diets rich in plant foods are associated with a lower risk of ischaemic heart disease (IHD), but there is sparse information on fruit and vegetable subtypes and sources of dietary fibre. This study examined the associations of major plant foods, their subtypes and dietary fibre with risk of IHD in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: We conducted a prospective analysis of 490 311 men and women without a history of myocardial infarction or stroke at recruitment (12.6 years of follow-up, n cases = 8504), in 10 European countries. Dietary intake was assessed using validated questionnaires, calibrated with 24-h recalls. Multivariable Cox regressions were used to estimate hazard ratios (HR) of IHD.Results: There was a lower risk of IHD with a higher intake of fruit and vegetables combined [HR per 200 g/day higher intake 0.94, 95% confidence interval (CI): 0.90–0.99, P-trend = 0.009], and with total fruits (per 100 g/day 0.97, 0.95–1.00, P-trend = 0.021). There was no evidence for a reduced risk for fruit subtypes, except for bananas. Risk was lower with higher intakes of nuts and seeds (per 10 g/day 0.90, 0.82–0.98, P-trend = 0.020), total fibre (per 10 g/day 0.91, 0.85–0.98, P-trend = 0.015), fruit and vegetable fibre (per 4 g/day 0.95, 0.91–0.99, P-trend = 0.022) and fruit fibre (per 2 g/day 0.97, 0.95–1.00, P-trend = 0.045). No associations were observed between vegetables, vegetables subtypes, legumes, cereals and IHD risk.Conclusions: In this large prospective study, we found some small inverse associations between plant foods and IHD risk, with fruit and vegetables combined being the most strongly inversely associated with risk. Whether these small associations are causal remains unclear.
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32.
  • Pham, Thu-Thi, et al. (författare)
  • Pre-diagnostic circulating resistin concentrations are not associated with colorectal cancer risk in the european prospective investigation into cancer and nutrition study
  • 2022
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:22
  • Tidskriftsartikel (refereegranskat)abstract
    • Resistin is a polypeptide implicated in inflammatory processes, and as such could be linked to colorectal carcinogenesis. In case-control studies, higher resistin levels have been found in colorectal cancer (CRC) patients compared to healthy individuals. However, evidence for the association between pre-diagnostic resistin and CRC risk is scarce. We investigated pre-diagnostic resistin concentrations and CRC risk within the European Prospective Investigation into Cancer and Nutrition using a nested case-control study among 1293 incident CRC-diagnosed cases and 1293 incidence density-matched controls. Conditional logistic regression models controlled for matching factors (age, sex, study center, fasting status, and women-related factors in women) and potential confounders (education, dietary and lifestyle factors, body mass index (BMI), BMI-adjusted waist circumference residuals) were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for CRC. Higher circulating resistin concentrations were not associated with CRC (RR per doubling resistin, 1.11; 95% CI 0.94–1.30; p = 0.22). There were also no associations with CRC subgroups defined by tumor subsite or sex. However, resistin was marginally associated with a higher CRC risk among participants followed-up maximally two years, but not among those followed-up after more than two years. We observed no substantial correlation between baseline circulating resistin concentrations and adiposity measures (BMI, waist circumference), adipokines (adiponectin, leptin), or metabolic and inflammatory biomarkers (C-reactive protein, C-peptide, high-density lipoprotein cholesterol, reactive oxygen metabolites) among controls. In this large-scale prospective cohort, there was little evidence of an association between baseline circulating resistin concentrations and CRC risk in European men and women.
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33.
  • Porta, Miquel, et al. (författare)
  • Plasma concentrations of persistent organic pollutants and pancreatic cancer risk
  • 2022
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 51:2, s. 479-490
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.Methods: We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.Results: Some associations were observed at higher concentrations of p, p'-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.Conclusions: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.
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34.
  • Rothwell, Joseph A., et al. (författare)
  • Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts
  • 2023
  • Ingår i: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts.Methods: Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases.Results: Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69–0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87–0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75–0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89–1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded.Conclusions: Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.
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35.
  • Rothwell, Joseph A., et al. (författare)
  • Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort
  • 2022
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:5, s. e1061-e1082
  • Tidskriftsartikel (refereegranskat)abstract
    • 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 and Nutrition 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 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs 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 increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly 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 with 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 a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.
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36.
  • Sasamoto, Naoko, et al. (författare)
  • Development and validation of circulating CA125 prediction models in postmenopausal women
  • 2019
  • Ingår i: Journal of Ovarian Research. - : BioMed Central (BMC). - 1757-2215. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker.Methods: We developed and validated linear and dichotomous (>= 35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset.Conclusions: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.
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37.
  • Sasamoto, Naoko, et al. (författare)
  • Predicting Circulating CA125 Levels among Healthy Premenopausal Women
  • 2019
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:6, s. 1076-1085
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (>= 35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.
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38.
  • Sobiecki, Jakub G., et al. (författare)
  • A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes : Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study
  • 2023
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 20:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker of the Mediterranean diet.Methods and findings: We derived a biomarker score based on 5 circulating carotenoids and 24 fatty acids that discriminated between the Mediterranean or habitual diet arms of a parallel design, 6-month partial-feeding randomised controlled trial (RCT) conducted between 2013 and 2014, the MedLey trial (128 participants out of 166 randomised). We applied this biomarker score in an observational study, the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, to assess the association of the score with T2D incidence over an average of 9.7 years of follow-up since the baseline (1991 to 1998). We included 22, 202 participants, of whom 9, 453 were T2D cases, with relevant biomarkers from an original case-cohort of 27, 779 participants sampled from a cohort of 340, 234 people. As a secondary measure of the Mediterranean diet, we used a score estimated from dietary-self report. Within the trial, the biomarker score discriminated well between the 2 arms; the cross-validated C-statistic was 0.88 (95% confidence interval (CI) 0.82 to 0.94). The score was inversely associated with incident T2D in EPIC-InterAct: the hazard ratio (HR) per standard deviation of the score was 0.71 (95% CI: 0.65 to 0.77) following adjustment for sociodemographic, lifestyle and medical factors, and adiposity. In comparison, the HR per standard deviation of the self-reported Mediterranean diet was 0.90 (95% CI: 0.86 to 0.95). Assuming the score was causally associated with T2D, higher adherence to the Mediterranean diet in Western European adults by 10 percentiles of the score was estimated to reduce the incidence of T2D by 11% (95% CI: 7% to 14%). The study limitations included potential measurement error in nutritional biomarkers, unclear specificity of the biomarker score to the Mediterranean diet, and possible residual confounding.Conclusions: These findings suggest that objectively assessed adherence to the Mediterranean diet is associated with lower risk of T2D and that even modestly higher adherence may have the potential to reduce the population burden of T2D meaningfully.
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39.
  • Špacírová, Zuzana, et al. (författare)
  • The cost-effectiveness of a uniform versus age-based threshold for one-off screening for prevention of cardiovascular disease
  • 2023
  • Ingår i: European Journal of Health Economics. - : Springer Science and Business Media LLC. - 1618-7598 .- 1618-7601. ; 24:7, s. 1033-1045
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this article was to assess the cost-effectiveness of screening strategies for cardiovascular diseases (CVD). A decision analytic model was constructed to estimate the costs and benefits of one-off screening strategies differentiated by screening age, sex and the threshold for initiating statin therapy (“uniform” or “age-adjusted”) from the Spanish NHS perspective. The age-adjusted thresholds were configured so that the same number of people at high risk would be treated as under the uniform threshold. Health benefit was measured in quality-adjusted life years (QALY). Transition rates were estimated from the European Prospective Investigation into Cancer and Nutrition (EPIC-CVD), a large multicentre nested case-cohort study with 12 years of follow-up. Unit costs of primary care, hospitalizations and CVD care were taken from the Spanish health system. Univariate and probabilistic sensitivity analyses were employed. The comparator was no systematic screening program. The base case model showed that the most efficient one-off strategy is to screen both men and women at 40 years old using a uniform risk threshold for initiating statin treatment (Incremental Cost-Effectiveness Ratio of €3,274/QALY and €6,085/QALY for men and women, respectively). Re-allocating statin treatment towards younger individuals at high risk for their age and sex would not offset the benefit obtained using those same resources to treat older individuals. Results are sensitive to assumptions about CVD incidence rates. To conclude, one-off screening for CVD using a uniform risk threshold appears cost-effective compared with no systematic screening. These results should be evaluated in clinical studies.
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40.
  • Zamora-Ros, Raul, et al. (författare)
  • Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
  • 2020
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:7, s. 1841-1850
  • Tidskriftsartikel (refereegranskat)abstract
    • Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77–1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80–1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55–2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.
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41.
  • Zheng, Ju-Sheng, et al. (författare)
  • Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries : a cross-sectional analysis in the EPIC-InterAct study
  • 2017
  • Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. Methods: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. Results: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. Conclusions: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.
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