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  • 1
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Kongress Medizin und Gesellschaft 2007; 20070917-20070921; Augsburg; DOC07gmds291 /20070906/
    Publication Date: 2007-09-07
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Keywords: COHORT ; colon ; HEALTH ; WOMEN ; POPULATIONS ; nutrition ; INFLAMMATORY MARKERS ; MENDELIAN RANDOMIZATION
    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.
    Type of Publication: Journal article published
    PubMed ID: 25043606
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  • 3
    Keywords: RECEPTOR ; EXPRESSION ; TYROSINE KINASE ; EPIDEMIOLOGY ; colon ; nutrition ; RECTAL-CANCER ; INSULIN-RESISTANCE ; MENDELIAN RANDOMIZATION ; INSTRUMENTS
    Abstract: Fetuin-A, also referred to as alpha2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 microg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 microg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development.
    Type of Publication: Journal article published
    PubMed ID: 25611809
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  • 4
    Abstract: Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case-control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses' Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer.
    Type of Publication: Journal article published
    PubMed ID: 28550647
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  • 5
    Keywords: BLOOD ; Germany ; MODEL ; MODELS ; SAMPLE ; SAMPLES ; METABOLISM ; SERA ; PLASMA ; AGE ; WOMEN ; MEN ; smoking ; PRODUCT ; DIETARY ; CONSUMPTION ; nutrition ; VEGETABLES ; FOOD ; LIFE-STYLE FACTORS ; DIETARY-INTAKE ; REGRESSION-MODELS ; carotenoids ; SERUM ; ELISA ; REGRESSION ; RE ; PRODUCTS ; DETERMINANTS ; ELDERLY-WOMEN ; TOCOPHEROL ; biomarker ; analysis ; methods ; TESTS ; correlation ; female ; Male ; UNIT ; COEFFICIENTS ; DAIRY-PRODUCTS ; LOGISTIC-REGRESSION ; correlates ; German ; PLASMA-CONCENTRATION ; Bavarian Food Consumption Survey II ; BONE-MINERAL DENSITY ; CARBOXYGLUTAMIC ACID ; dairy ; GAMMA-CARBOXYLATED OSTEOCALCIN ; GLA PROTEIN ; HIP FRACTURE ; K BIOCHEMICAL MEASURES ; PLASMA PHYLLOQUINONE VITAMIN-K-1 ; undercarboxylated osteocalcin ; VALUES ; vitamin K
    Abstract: Background/Aims: To assess dietary and nondietary determinants of serum undercarboxylated osteocalcin (ucOC) as a measure of vitamin K status. Methods: UcOC and total intact osteocalcin (iOC) concentrations were determined by specific ELISA tests in serum samples of 231 male and 320 female participants (18-81 years) of the representative, cross-sectional Bavarian Food Consumption Survey II. Determinants of ucOC were investigated by analysis of variance, Spearman's rank correlation coefficients and logistic regression models. Results: Mean ucOC serum concentration was 2.46 ng/ml in men and 2.34 ng/ml in women. Corresponding means of the ratio of ucOC to iOC (ucOC/iOC) were 0.28 and 0.29. Concentrations of ucOC and iOC, as well as the ratio of ucOC/iOC, strongly depended on the participant's age. UcOC was influenced by smoking status, sports activity, and the season when blood was collected. Dietary intake of the dominant vitamin K sources, green leafy vegetables and dairy products, as well as the plasma concentration of the carotenoid lutein were inversely associated with serum ucOC values. Conclusions: In studies using serum ucOC as a measure of vitamin K supply, determinants, especially age, need to be taken into account. Copyright (c) 2008 S. Karger AG, Basel
    Type of Publication: Journal article published
    PubMed ID: 18227625
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  • 6
    Keywords: CANCER ; CANCER CELLS ; CELLS ; CELL ; Germany ; PROSTATE ; FOLLOW-UP ; COHORT ; HEPATOCELLULAR-CARCINOMA ; incidence ; RISK ; RISKS ; GENE-EXPRESSION ; TIME ; CELL-LINES ; ASSOCIATION ; ANTITUMOR-ACTIVITY ; DESIGN ; MEN ; prostate cancer ; PROSTATE-CANCER ; CANCER-CELLS ; DIETARY ; nutrition ; QUESTIONNAIRE ; RELATIVE RISK ; DIETARY-INTAKE ; PERFORMANCE LIQUID-CHROMATOGRAPHY ; REGRESSION ; RE ; USA ; CANCER INCIDENCE ; TISSUE DISTRIBUTION ; vitamin K ; BRITISH ELDERLY PEOPLE ; FAST-FOOD ; NATIONAL SAMPLE ; PHYLLOQUINONE VITAMIN-K-1
    Abstract: Background: Anticarcinogenic activities of vitamin K have been observed in various cancer cell lines, including prostate cancer cells. Epidemiologic studies linking dietary intake of vitamin K with the development of prostate cancer have not yet been conducted. Objective: We evaluated the association between dietary intake of phylloquinone (vitamin K1) and menaquinones (vitamin K2) and total and advanced prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. Design: At baseline, habitual dietary intake was assessed by means of a food-frequency questionnaire. Dietary intake of phylloquitione and menaquinones (MK-4-14) was estimated by using previously published HPLC-based food-content data. Multivariate-adjusted relative risks of total and advanced prostate cancer in relation to intakes of phylloquitione and menaquinones were calculated in 11319 men by means of Cox proportional hazards regression. Results: During a mean follow-up time of 8.6 y, 268 incident cases of prostate cancer, including 113 advanced cases, were identified. We observed a nonsignificant inverse association between total prostate cancer and total menaquinone intake [multivariate relative risk (highest compared with lowest quartile): 0.65; 95% Cl: 0.39, 1.06]. The association was stronger for advanced prostate cancer (0.37; 0.16, 0.88; P for trend = 0.03). Menaquinones from dairy products had a stronger inverse association with advanced prostate cancer than did menaquinones from meat. Phylloquinone intake was unrelated to prostate cancer incidence (1.02; 0.70, 1.48). Conclusions: Our results suggest an inverse association between the intake of menaquinones, but not that of phylloquinone, and prostate cancer. Further studies of dietary vitamin K and prostate cancer are warranted
    Type of Publication: Journal article published
    PubMed ID: 18400723
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  • 7
    Keywords: Germany ; MODEL ; MODELS ; GENE ; PROTEIN ; PROTEINS ; SAMPLE ; SAMPLES ; ASSOCIATION ; polymorphism ; VARIANTS ; FORM ; WOMEN ; MEN ; CONSUMPTION ; nutrition ; PERFORMANCE LIQUID-CHROMATOGRAPHY ; SERUM ; REGRESSION ; VARIANT ; CORONARY-HEART-DISEASE ; PROMOTER POLYMORPHISM ; biomarker ; GENOTYPE ; TESTS ; dietary intake ; BONE-MINERAL DENSITY ; CARBOXYGLUTAMIC ACID ; HIP FRACTURE ; undercarboxylated osteocalcin ; vitamin K ; BRITISH ELDERLY PEOPLE ; PHYLLOQUINONE VITAMIN-K-1 ; PHYLLOQUINONE ; VKORC1 ; GAMMA-GLUTAMYL CARBOXYLASE ; Menaquinones ; PLASMA PHYLLOQUINONE
    Abstract: Vitamin K acts as a cofactor during the gamma-carboxylation of vitamin K-dependent proteins. Undercarboxylated osteocalcin (ucOC) is a suggested biomarker of vitamin K status. The +2255 polymorphism of the vitamin K epoxide reductase gene (VKORC1) was shown to be associated with the recycling rate of the active form of vitamin K. We investigated the association between dietary vitamin K intake and serum ucOC and hypothesized that this association might vary by VKORC1 genotype. ucOC and total intact osteocalcin (iOC) concentrations were quantified using specific ELISA tests in serum samples of 548 male and female participants (aged 18-81 years) of the Bavarian Food Consumption Survey II. ucOC was expressed relative to iOC (ucOC/iOC ratio). Dietary intake of vitamin K (phylloquinone and menaquinones) was estimated from three 24 h dietary recalls using previously published food composition data. The association between dietary vitamin K intake and ucOC/iOC ratio was analysed using linear and non-linear regression models. Median intakes of phylloquinone/menaquinones were 83-4/37.6 mu g/d in men and 79-6/29-8 mu g/d in women, respectively. As expected, vitamin K intake was significantly inversely associated with the ucOC/iCC ratio. The ucOC/iOC ratio differed significantly across variants of the +2255 polymorphism in the VKORC1 gene. Stratification by VKORC1 + 2255 genotype revealed that only in carriers of the GG genotype (39% of all participants) did the ucOC/iOC ratio significantly decrease with increasing intake of vitamin K. Thus, the results show that the inverse association between dietary vitamin K intake and serum ucOC depends on a functionally relevant allelic variant of the VKORC1 gene
    Type of Publication: Journal article published
    PubMed ID: 19025725
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  • 8
    Keywords: CANCER ; CELLS ; tumor ; CELL ; Germany ; MODEL ; PROSTATE ; FOLLOW-UP ; COHORT ; cohort study ; POPULATION ; RISK ; TIME ; ASSOCIATION ; FREQUENCIES ; STAGE ; REPRODUCIBILITY ; prostate cancer ; PROSTATE-CANCER ; cancer risk ; DATABASE ; RECRUITMENT ; PROJECT ; CONSUMPTION ; VEGETABLES ; FOOD-INTAKE ; FOOD FREQUENCY QUESTIONNAIRE ; METABOLITE ; PRODUCTS ; prospective studies ; RELATIVE VALIDITY ; bioavailability ; USA ; dietary intake ; prospective ; prospective study ; EPIC-Heidelberg ; CANCERS ; CANCER-RISK ; FOODS ; NOV ; LOW-GRADE ; GERMAN PART ; PLANT FOODS ; hazard ratio ; RANGE ; CRUCIFEROUS VEGETABLES ; Food content ; Glucosinolates ; FRUIT CONSUMPTION
    Abstract: Glucosinolates (GLS) are secondary plant metabolites occurring in cruciferous vegetables. Their biologically active break-down products show cancer preventive properties in animal and cell studies. So far, epidemiologic studies, using consumption of cruciferous vegetables as proxy for GLS intake, yielded inconsistent results. Here, we evaluated the association between dietary intake of GLS in comparison with consumption data of GLS-containing foods and the risk of prostate cancer. The study population comprised 11,405 male participants of the prospective EPIC-Heidelberg cohort study. During a mean follow-up time of 9.4 years, 328 incident cases of prostate cancer occurred. At recruitment, habitual food consumption was assessed by a validated food frequency questionnaire, and intake of individual GLS was estimated by means of a newly compiled database on food content of GLS. Adjusted hazard ratios (HR) for prostate cancer were calculated using the Cox proportional hazard model. Median daily intake of total GLS was 7.9 mg/day (interquartile range 5.1-11.9 mg/day). The risk of prostate cancer decreased significantly over quartiles of total GLS intake (multivariate HR [4th vs. 1st quartile] 0.68, 95% CI 0.48-4.97, P-trend 0.03). Associations with GLS-containing food intake were weaker. Among GLS subgroups, aliphatic GLS showed the strongest inverse association with cancer risk. Analyse stratified by tumor stage and grade gave hint to inverse associations for localized and low-grade cancers. This study shows an inverse association between dietary intake of GLS and the risk of prostate cancer. Because this is the first prospective study using individual GLS intake data, confirmation in other studies is warranted. (C) 2009 UICC
    Type of Publication: Journal article published
    PubMed ID: 19585501
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  • 9
    Keywords: USA ; EPIC-Heidelberg ; dietary intake ; HEALTH ; CANCER ; MORTALITY ; COHORT
    Type of Publication: Meeting abstract published
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  • 10
    Keywords: undercarboxylated osteocalcin ; vitamin K ; CANCER-RISK ; USA ; SERUM ; DIETARY ; HEALTH ; PROSTATE-CANCER ; prostate cancer ; cancer risk ; CANCER ; PROSTATE ; RISK
    Type of Publication: Meeting abstract published
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