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Sökning: WFRF:(Gunter Marc J.) > Ardanaz Eva

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1.
  • Aleksandrova, Krasimira, et al. (författare)
  • A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
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2.
  • Kong, So Yeon, et al. (författare)
  • The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk
  • 2015
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:12, s. 1855-1863
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A large proportion of colorectal cancers are thought to be associated with unhealthy dietary and lifestyle exposures, particularly energy excess, obesity, hyperinsulinemia, and hyperglycemia. It has been suggested that these processes stimulate the production of toxic reactive carbonyls from sugars such as glyceraldehyde. Glyceraldehyde contributes to the production of a group of compounds known as glyceraldehyde-derived advanced glycation end-products (glycer-AGEs), which may promote colorectal cancer through their proinflammatory and pro-oxidative properties. The objective of this study nested within a prospective cohort was to explore the association of circulating glycer-AGEs with risk of colorectal cancer. Methods: A total of 1,055 colorectal cancer cases (colon n = 659; rectal n = 396) were matchced (1: 1) to control subjects. Circulating glycer-AGEs were measured by a competitive ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (95% CI), adjusting for potential confounding factors, including smoking, alcohol, physical activity, body mass index, and diabetes status. Results: Elevated glycer-AGEs levels were not associated with colorectal cancer risk (highest vs. lowest quartile, 1.10; 95% CI, 0.82-1.49). Subgroup analyses showed possible divergence by anatomical subsites (OR for colon cancer, 0.83; 95% CI, 0.571.22; OR for rectal cancer, 1.90; 95% CI, 1.14-3.19; Pheterogeneity = 0.14). Conclusions: In this prospective study, circulating glycer-AGEs were not associated with risk of colon cancer, but showed a positive association with the risk of rectal cancer. Impact: Further research is needed to clarify the role of toxic products of carbohydrate metabolism and energy excess in colorectal cancer development. 
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3.
  • Kroeger, Janine, et al. (författare)
  • Circulating Fetuin-A and Risk of Type 2 Diabetes : A Mendelian Randomization Analysis
  • 2018
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 67:6, s. 1200-1205
  • Tidskriftsartikel (refereegranskat)abstract
    • Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.
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4.
  • Li, Sherly X, et al. (författare)
  • Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.
  • 2018
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 61:6, s. 1325-1332
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes.We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution.No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined.Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.
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5.
  • Seyed Khoei, Nazlisadat, et al. (författare)
  • Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses
  • 2020
  • Ingår i: BMC Medicine. - : Springer Nature. - 1741-7015. ; 18:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2).CONCLUSIONS: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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6.
  • Aglago, Elom K., et al. (författare)
  • Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk : A Case-Control Study Nested within a European Prospective Cohort
  • 2021
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:1, s. 182-192
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
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7.
  • Duarte-Salles, Talita, et al. (författare)
  • Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population
  • 2016
  • Ingår i: Cancer Prevention Research. - 1940-6207 .- 1940-6215. ; 9:9, s. 758-765
  • Tidskriftsartikel (refereegranskat)abstract
    • We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and a-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis.
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8.
  • Imamura, Fumiaki, et al. (författare)
  • A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes : The EPIC-InterAct case-cohort study
  • 2017
  • Ingår i: PLoS Medicine. - : Public Library Science. - 1549-1277 .- 1549-1676. ; 14:10
  • 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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9.
  • Rolandsson, Olov, et al. (författare)
  • Autoimmunity plays a role in the onset of diabetes after 40 years of age
  • 2020
  • Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63, s. 266-277
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort.Methods: GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression.Results: GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors.Conclusions/interpretation: Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.
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10.
  • Sanikini, Harinakshi, et al. (författare)
  • Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite : Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
  • 2020
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 146:4, s. 929-942
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.
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