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11.
  • Hughes, David J, et al. (författare)
  • Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort.
  • 2015
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:5, s. 1149-1161
  • Tidskriftsartikel (refereegranskat)abstract
    • Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe. Low Se status may contribute to colorectal cancer (CRC) development. We assessed Se status by measuring serum levels of Se and Selenoprotein P (SePP) and examined the association with CRC risk in a nested case-control design (966 CRC cases; 966 matched controls) within the European Prospective Investigation into Cancer and Nutrition. Se was measured by total reflection X-ray fluorescence and SePP by immunoluminometric sandwich assay. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non-significant lower CRC risk (IRR = 0.92, 95% CI: 0.82-1.03 per 25 μg/L increase). However, sub-group analyses by sex showed a statistically significant association for women (ptrend  = 0.032; per 25 μg/L Se increase, IRR = 0.83, 95% CI: 0.70-0.97) but not for men. Higher SePP concentrations were inversely associated with CRC risk (ptrend  = 0.009; per 0.806 mg/L increase, IRR = 0.89, 95% CI: 0.82-0.98) with the association more apparent in women (ptrend  = 0.004; IRR = 0.82, 95% CI: 0.72-0.94 per 0.806 mg/L increase) than men (ptrend  = 0.485; IRR = 0.98, 95% CI: 0.86-1.12 per 0.806 mg/L increase). The findings indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women.
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12.
  • Nimptsch, Katharina, et al. (författare)
  • Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk.
  • 2015
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:5, s. 1181-1192
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8-19%). Using the CRP-score as instrumental variable, genetically twofold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06-2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer.
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13.
  • van Duijnhoven, Fraenzel J. B., et al. (författare)
  • Circulating concentrations of vitamin D in relation to pancreatic cancer risk in European populations
  • 2018
  • Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 142:6, s. 1189-1201
  • Tidskriftsartikel (refereegranskat)abstract
    • Evidence from in vivo, in vitro and ecological studies are suggestive of a protective effect of vitamin D against pancreatic cancer (PC). However, this has not been confirmed by analytical epidemiological studies. We aimed to examine the association between pre-diagnostic circulating vitamin D concentrations and PC incidence in European populations. We conducted a pooled nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nord-TrOndelag Health Study's second survey (HUNT2) cohorts. In total, 738 primary incident PC cases (EPIC n=626; HUNT2 n=112; median follow-up=6.9 years) were matched to 738 controls. Vitamin D [25(OH)D-2 and 25(OH)D-3 combined] concentrations were determined using isotope-dilution liquid chromatography-tandem mass spectrometry. Conditional logistic regression models with adjustments for body mass index and smoking habits were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95%CI). Compared with a reference category of >50 to 75 nmol/L vitamin D, the IRRs (95% CIs) were 0.71 (0.42-1.20); 0.94 (0.72-1.22); 1.12 (0.82-1.53) and 1.26 (0.79-2.01) for clinically pre-defined categories of 25; >25 to 50; >75 to 100; and >100 nmol/L vitamin D, respectively (p for trend=0.09). Corresponding analyses by quintiles of season-standardized vitamin D concentrations also did not reveal associations with PC risk (p for trend=0.23). Although these findings among participants from the largest combination of European cohort studies to date show increasing effect estimates of PC risk with increasing pre-diagnostic concentrations of vitamin D, they are not statistically significant.
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15.
  • Lukanova, Annekatrin, et al. (författare)
  • Pre-diagnostic plasma testosterone, sex hormone binding globulin, IGF-I and hepatocellular carcinoma : etiological factors or risk markers?
  • 2014
  • Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 134:1, s. 164-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated pre-diagnostic testosterone and insulin-like growth factor-I (IGF-I) concentrations have been proposed to increase risk of hepatocellular carcinoma (HCC). However, the metabolism of these hormones is altered as a consequence of liver damage and they may have clinical utility as HCC risk markers. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and included 125 incident HCC cases and 247 individually matched controls. Testosterone, sex hormone binding globulin (SHBG) and IGF-I were analyzed by immunoassays. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression. The area under the receiver operating curves (AUC) was calculated to assess HCC predictive ability of the tested models. After adjustments for epidemiological variables (body mass index, smoking, ethanol intake, hepatitis and diabetes) and liver damage (a score based on albumin, bilirubin, aspartate aminotransaminase, alanine aminotransaminase, gamma-glutamyltransferase and alkaline phosphatase concentrations), only SHBG remained significantly associated with risk (OR for top versus bottom tertile of 3.86 (1.32-11.3), ptrend =0.009). As a single factor SHBG had an AUC of 0.81 (0.75-0.86). A small, but significant increase in AUC was observed when SHBG was added to a model including the liver damage score and epidemiological variables (from 0.89 to 0.91, p=0.02) and a net reclassification of 0.47% (0.45-0.48). The observed associations of HCC with pre-diagnostic SHBG, free testosterone and IGF-I concentrations are in directions opposite to that expected under the etiological hypotheses. SHBG has a potential to be tested as pre-diagnostic risk marker for HCC.
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16.
  • Boeing, Heiner, et al. (författare)
  • Intake of fruits and vegetables and risk of cancer of the upper aero-digestive tract: the prospective EPIC-study
  • 2006
  • Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 17:7, s. 957-969
  • Tidskriftsartikel (refereegranskat)abstract
    • Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (< 120 g/d) for fruits. Dietary recommendations should consider the potential benefit of increasing fruits and vegetables consumption for reducing the risk of cancers of the upper aero-digestive tract, particularly at low intake.
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17.
  • Naudin, Sabine, et al. (författare)
  • Healthy lifestyle and the risk of pancreatic cancer in the EPIC study
  • 2020
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 35:10, s. 975-986
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic cancer (PC) is a highly fatal cancer with currently limited opportunities for early detection and effective treatment. Modifiable factors may offer pathways for primary prevention. In this study, the association between the Healthy Lifestyle Index (HLI) and PC risk was examined. Within the European Prospective Investigation into Cancer and Nutrition cohort, 1113 incident PC (57% women) were diagnosed from 400,577 participants followed-up for 15 years (median). HLI scores combined smoking, alcohol intake, dietary exposure, physical activity and, in turn, overall and central adiposity using BMI (HLIBMI) and waist-to-hip ratio (WHR, HLIWHR), respectively. High values of HLI indicate adherence to healthy behaviors. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and 95% confidence intervals (CI). Sensitivity analyses were performed by excluding, in turn, each factor from the HLI score. Population attributable fractions (PAF) were estimated assuming participants’ shift to healthier lifestyles. The HRs for a one-standard deviation increment of HLIBMI and HLIWHR were 0.84 (95% CI: 0.79, 0.89; ptrend = 4.3e−09) and 0.77 (0.72, 0.82; ptrend = 1.7e−15), respectively. Exclusions of smoking from HLIWHR resulted in HRs of 0.88 (0.82, 0.94; ptrend = 4.9e−04). The overall PAF estimate was 19% (95% CI: 11%, 26%), and 14% (6%, 21%) when smoking was removed from the score. Adherence to a healthy lifestyle was inversely associated with PC risk, beyond the beneficial role of smoking avoidance. Public health measures targeting compliance with healthy lifestyles may have an impact on PC incidence.
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18.
  • Rohrmann, Sabine, et al. (författare)
  • Ethanol intake and risk of lung cancer in the European prospective investigation into cancer and nutrition (EPIC)
  • 2006
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 164:11, s. 1103-1114
  • Tidskriftsartikel (refereegranskat)abstract
    • Within the European Prospective Investigation into Cancer and Nutrition (EPIC), the authors examined the association of ethanol intake at recruitment (1,119 cases) and mean lifelong ethanol intake (887 cases) with lung cancer. Information on baseline and past alcohol consumption, lifetime tobacco smoking, diet, and the anthropometric characteristics of 478,590 participants was collected between 1992 and 2000. Cox proportional hazards regression was used to calculate multivariate-adjusted hazard ratios and 95% confidence intervals. Overall, neither ethanol intake at recruitment nor mean lifelong ethanol intake was significantly associated with lung cancer. However, moderate intake (5-14.9 g/day) at recruitment (hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.63, 0.90) and moderate mean lifelong intake (HR = 0.80, 95% CI: 0.66, 0.97) were associated with a lower lung cancer risk in comparison with low consumption (0.1-4.9 g/day). Compared with low intake, a high (>= 60 g/day) mean lifelong ethanol intake tended to be related to a higher risk of lung cancer (HR = 1.29, 95% CI: 0.93, 1.74), but high intake at recruitment was not. Although there was no overall association between ethanol intake and risk of lung cancer, the authors cannot rule out a lower risk for moderate consumption and a possibly increased risk for high lifelong consumption.
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19.
  • Weikert, Cornelia, et al. (författare)
  • Lifetime and baseline alcohol intake and risk of cancer of the upper aero-digestive tract in the European prospective investigation into cancer and nutrition (EPIC) study
  • 2009
  • Ingår i: International Journal of Cancer. - Geneve : Wiley. - 0020-7136 .- 1097-0215. ; 125:2, s. 406-412
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent alcohol consumption is all established risk factor for squamous cell carcinoma (SCC) or the upper aero-digestive tract. In contrast, the role or lifetime exposure to alcohol with regard to risk of SCC is not well established. Historical data oil alcohol use are available in 271,253 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). During 2,330,381 person years, 392 incident SCC cases (279 men and 113 women) were identified. Cox regression vas applied to model sex-specific associations between lifetime alcohol intake and SCC risk adjusting for potential confounders including smoking. Compared to men who drank 0.1-6.0 g/day alcohol at lifetime, the relative risks (RR) for developing SCC were significantly increased for men who drank 30.1-60.0 g/day (RR 1.65, 95% confidence interval: 1.00-2.71), 60.1-96.0 g/day (RR 2.20, 95%CI 1.23-3.95), and >96.0 g/day, (RR 4.63, 95% CI 2.52-8.48), and for former drinkers (RR 4.14, 95% CI 2.38-7.19). These risk estimates did not considerably change when baseline alcohol intake was analyzed. Compared to women who drank 0.1-6.0 g/day alcohol intake at lifetime, the RR were significantly increased for women who drank >30 g/d (RR 6.05, 95% CI 2.98-12.3). Applying similar categories, the relative risk for baseline alcohol intake was 3.26 (95%CI 1.82-5.87). We observed a stronger association between alcohol intake at lifetime and risk of SCC in women compared to men (p for interaction = 0.045). The strong dose-response relation for lifetime alcohol use underscores that alcohol is an important risk factor of SCC of the upper aero-digestive tract throughout life. (C) 2009 UICC
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20.
  • Aleksandrova, Krasimira, et al. (författare)
  • Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer : results from the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2014
  • Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 29:4, s. 261-275
  • Tidskriftsartikel (refereegranskat)abstract
    • A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60 % of the overall biomarker variance. In multivariable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95 % CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95 % CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95 % CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95 % CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development.
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