| 1. |
- Aleksandrova, Krasimira, et al.
(författare)
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The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury : data from the European Prospective Investigation into Cancer and Nutrition
- 2015
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Ingår i: American Journal of Clinical Nutrition. - : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 102:6, s. 1498-1508
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Tidskriftsartikel (refereegranskat)abstract
- Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having >= 4 cups (600mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.
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| 2. |
- Fedirko, Veronika, et al.
(författare)
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Pre-diagnostic anthropometry and survival after colorectal cancer diagnosis in Western European populations
- 2014
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 135:8, s. 1949-1960
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Tidskriftsartikel (refereegranskat)abstract
- General and abdominal adiposity are associated with a high risk of developing colorectal cancer (CRC), but the role of these exposures on cancer survival has been less studied. The association between pre-diagnostic anthropometric characteristics and CRC-specific and all-cause death was examined among 3,924 men and women diagnosed with CRC between 1992 and 2009 in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Multivariable Cox proportional hazards models were used to calculate hazard ratios (FIRS) and corresponding 95% confidence intervals (as). Over a mean follow-up period of 49 months, 1,309 deaths occurred of which 1,043 (79.7%) were due to CRC. In multivariable analysis, prediagnostic BMI kg/m2 was associated with a high risk for CRC-specific (HR = 1.26, 95% CI = 1.04-1.52) and all-cause (HR = 1.32, 95% CI = 1.12-1.56) death relative to BMI <25 kg/m(2). Every 5 kg/m(2) increase in BMI was associated with a high risk for CRC-specific (HR = 1.10, 95% CI = 1.02-1.19) and all-cause death (HR = 1.12, 95% Cl = 1.05-1.20); and every 10 cm increase in waist circumference was associated with a high risk for CRC-specific (HR = 1.09, 95% Cl = 1.02-1.16) and allcause death (HR= 1.11, 95% CI= 1.05-1.18). Similar associations were observed for waist-to-hip and waist-to-height ratios. Height was not associated with CRC-specific or all-cause death. Associations tended to be stronger among men than in women. Possible interactions by age at diagnosis, cancer stage, tumour location, and hormone replacement therapy use among postmenopausal women were noted. Pre-diagnostic general and abdominal adiposity are associated with lower survival after CRC diagnosis.
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| 3. |
- Fedirko, Veronika, et al.
(författare)
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Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations
- 2019
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Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 11:8
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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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| 4. |
- Kong, So Yeon, et al.
(författare)
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Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort
- 2016
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 25:2, s. 291-301
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk. Methods: A total of 1,065 incident colorectal cancer cases (colon, n = 667; rectal, n = 398) were matched (1:1) to control subjects. Serum flagellin-and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors. Results: Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with colorectal cancer risk. After testing potential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (P-interaction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS + flagellin, 1.66; 95% CI, 1.10-2.51; P-trend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47-1.02; P-trend, 0.18). Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist. Impact: Further studies are warranted to better clarify these preliminary observations. (C) 2016 AACR.
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| 5. |
- Kong, So Yeon, et al.
(författare)
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The Association between Glyceraldehyde-Derived Advanced Glycation End-Products and Colorectal Cancer Risk
- 2015
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 24:12, s. 1855-1863
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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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| 6. |
- Rohrmann, Sabine, et al.
(författare)
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Meat and fish consumption and the risk of renal cell carcinoma in the European prospective investigation into cancer and nutrition
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:5, s. 423-431
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Tidskriftsartikel (refereegranskat)abstract
- Renal cell cancer (RCC) incidence varies worldwide with a higher incidence in developed countries and lifestyle is likely to contribute to the development of this disease. We examined whether meat and fish consumption were related to the risk of RCC in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 493,179 EPIC participants, recruited between 1992 and 2000. Until December 2008, 691 RCC cases have been identified. Meat and fish consumption was assessed at baseline using country-specific dietary assessment instruments; 24-hour recalls were applied in an 8% subsample for calibration purposes. Cox proportional hazards regression was used to calculate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). Women with a high consumption of red meat (HR=1.36, 95% CI 1.14-1.62; calibrated, per 50 g/day) and processed meat (HR=1.78, 95% CI 1.05-3.03; calibrated, per 50 g/day) had a higher risk of RCC, while no association existed in men. For processed meat, the association with RCC incidence was prominent in premenopausal women and was lacking in postmenopausal women (p interaction=0.02). Neither poultry nor fish consumption were statistically significantly associated with the risk of RCC. The results show a distinct association of red and processed meat consumption with incident RCC in women but not in men. A biological explanation for these findings remains unclear. What's new? Kidney cancer strikes different populations with different frequency, with developed nations seeing more cases. In this paper, the authors investigate whether certain elements of diet might correlate with increased incidence of renal cell carcinoma. Using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), they assessed the amount of meat and fish consumed in populations representing a wide range of dietary habits. They then correlated this data with renal cell carcinoma incidence. They found no effect from eating fish; consuming red and processed meats did increase risk in women, but not in men.
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| 7. |
- Sen, Abhijit, et al.
(författare)
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Baseline and lifetime alcohol consumption and risk of differentiated thyroid carcinoma in the EPIC study
- 2015
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 113:5, s. 840-847
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Tidskriftsartikel (refereegranskat)abstract
- Background: Results from several cohort and case-control studies suggest a protective association between current alcohol intake and risk of thyroid carcinoma, but the epidemiological evidence is not completely consistent and several questions remain unanswered. Methods: The association between alcohol consumption at recruitment and over the lifetime and risk of differentiated thyroid carcinoma was examined in the European Prospective Investigation into Cancer and Nutrition. Among 477 263 eligible participants (70% women), 556 (90% women) were diagnosed with differentiated thyroid carcinoma over a mean follow-up of 11 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox proportional hazards models. Results: Compared with participants consuming 0.1-4.9 g of alcohol per day at recruitment, participants consuming 15 or more grams (approximately 1-1.5 drinks) had a 23% lower risk of differentiated thyroid carcinoma (HR = 0.77; 95% CI = 0.60-0.98). These findings did not differ greatly when analyses were conducted for lifetime alcohol consumption, although the risk estimates were attenuated and not statistically significant anymore. Similar results were observed by type of alcoholic beverage, by differentiated thyroid carcinoma histology or according to age, sex, smoking status, body mass index and diabetes. Conclusions: Our study provides some support to the hypothesis that moderate alcohol consumption may be associated with a lower risk of papillary and follicular thyroid carcinomas.
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| 8. |
- Stepien, Magdalena, et al.
(författare)
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Prospective association of liver function biomarkers with development of hepatobiliary cancers
- 2016
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Ingår i: Cancer Epidemiology. - : Elsevier. - 1877-7821 .- 1877-783X. ; 40, s. 179-187
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers. Methods: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95% CI). Results: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT) = 4.23, 95% CI: 2.72-6.59; OR(ALP) = 3.43, 95% CI: 2.31-5.10; OR(AST) = 3.00, 95% CI: 2.04-4.42; OR(ALT) = 2.69, 95% CI: 1.89-3.84; OR(Bilirubin) = 2.25, 95% CI: 1.58-3.20). Each liver enzyme (OR(GGT) = 4.98; 95% CI: 1.75-14.17; OR(AST) = 3.10, 95% CI: 1.04-9.30; OR(ALT) = 2.86, 95% CI: 1.26-6.48, OR(ALP) = 2.31, 95% CI: 1.10-4.86) but not bilirubin (OR(Bilirubin) = 1.46,95% CI: 0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR (ALP) = 1.59, 95% CI: 1.20-2.09). Conclusion: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.
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| 9. |
- Zamora-Ros, Raul, et al.
(författare)
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Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:3, s. 449-459
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Tidskriftsartikel (refereegranskat)abstract
- Fruit and vegetable (F&V) intake is considered as probably protective against overall cancer risk, but results in previous studies are not consistent for thyroid cancer (TC). The purpose of this study is to examine the association between the consumption of fruits, vegetables, fruit juices and differentiated thyroid cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The EPIC study is a cohort including over half a million participants, recruited between 1991 and 2000. During a mean follow-up of 14 years, 748 incident first primary differentiated TC cases were identified. F&V and fruit juice intakes were assessed through validated country-specific dietary questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Comparing the highest versus lowest quartile of intake, differentiated TC risk was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68-1.15; p-trend=0.44), vegetables (HR: 0.89; 95% CI: 0.69-1.14; p-trend=0.56), or fruit (HR: 1.00; 95% CI: 0.79-1.26; p-trend=0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98-1.53; p-trend=0.06). This study did not find any significant association between F&V intakes and differentiated TC risk; however a positive trend with fruit juice intake was observed, possibly related to its high sugar content.
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| 10. |
- Zamora-Ros, Raul, et al.
(författare)
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Dietary Intakes of Individual Flavanols and Flavonols Are Inversely Associated with Incident Type 2 Diabetes in European Populations
- 2014
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Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 144:3, s. 335-343
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Tidskriftsartikel (refereegranskat)abstract
- Dietary flavanols and flavonols, flavonoid subclasses, have been recently associated with a lower risk of type 2 diabetes (T2D) in Europe. Even within the same subclass, flavonoids may differ considerably in bioavailability and bioactivity. We aimed to examine the association between individual flavanol and flavonol intakes and risk of developing T2D across European countries. The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study was conducted in 8 European countries across 26 study centers with 340,234 participants contributing 3.99 million person-years of follow-up, among whom 12,403 incident T2D cases were ascertained and a center-stratified subcohort of 16,154 individuals was defined. We estimated flavonoid intake at baseline from validated dietary questionnaires using a database developed from Phenol-Explorer and USDA databases. We used country-specific Prentice-weighted Cox regression models and random-effects meta-analysis methods to estimate HRs. Among the flavanol subclass, we observed significant inverse trends between intakes of all individual flavan-3-ol monomers and risk of T2D in multivariable models (all P-trend < 0.05). We also observed significant trends for the intakes of proanthocyanidin dimers (HR for the highest vs. the lowest quintile. 0.81; 95% Cl: 0.71, 0.92; P-trend = 0.003) and trimers (HR: 0.91; 95% Cl: 0.80, 1.04; P-trend = 0.07) but not for proanthocyanidins with a greater polymerization degree. Among the flavonol subclass, myricetin (HR: 0.77; 95% Cl: 0.64, 0.93; P-trend = 0.001) was associated with a lower incidence of T2D. This large and heterogeneous European study showed inverse associations between all individual flavan-3-ol monomers, proanthocyanidins with a low polymerization degree, and the flavonol myricetin and incident T2D. These results suggest that individual flavonoids have different roles in the etiology of T2D.
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