| 1. |
- Bamia, Christina, et al.
(författare)
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Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: Multicentre, prospective cohort study
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136, s. 1899-1908
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Tidskriftsartikel (refereegranskat)abstract
- © 2014 UICC. Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend < 0.001]. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22-0.78, p-trend50.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p-trend50.009), but not decaffeinated (p-trend50.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects.
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| 2. |
- Duarte-Salles, Talita, et al.
(författare)
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Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort
- 2015
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 137:11, s. 2715-2728
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Tidskriftsartikel (refereegranskat)abstract
- The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.
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| 3. |
- Fonseca-Nunes, Ana, et al.
(författare)
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Body iron status and gastric cancer risk in the EURGAST study.
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:12, s. 2904-2914
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Tidskriftsartikel (refereegranskat)abstract
- Although it appears biologically plausible for iron to be associated with gastric carcinogenesis, the evidence is insufficient to lead to any conclusions. To further investigate the relationship between body iron status and gastric cancer risk, we conducted a nested case-control study in the multicentric European Prospective Investigation into Cancer and Nutrition (EPIC) study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured prediagnostic serum iron, ferritin, transferrin and C-reactive protein, and further estimated total iron-binding capacity (TIBC) and transferrin saturation (TS). Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by iron metrics were estimated from multivariable conditional logistic regression models. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and ferritin and TS indices (ORlog2 = 0.80, 95% CI = 0.72-0.88; OR10%increment = 0.87, 95% CI = 0.78-0.97, respectively). These associations appear to be restricted to noncardia gastric cancer (ferritin showed a p for heterogeneity = 0.04 and TS had a p for heterogeneity = 0.02), and no differences were found by histological type. TIBC increased risk of overall gastric cancer (OR50 µg/dl = 1.13, 95% CI = 1.02-1.2) and also with noncardia gastric cancer (p for heterogeneity = 0.04). Additional analysis suggests that time between blood draw and gastric cancer diagnosis could modify these findings. In conclusion, our results showed a decreased risk of gastric cancer related to higher body iron stores as measured by serum iron and ferritin. Further investigation is needed to clarify the role of iron in gastric carcinogenesis.
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| 4. |
- Huang, Jiaqi, et al.
(författare)
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Helicobacter pylori infection, chronic corpus atrophic gastritis and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort : A nested case-control study
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 140:8, s. 1727-1735
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Tidskriftsartikel (refereegranskat)abstract
- The association between H. pylori infection and pancreatic cancer risk remains controversial. We conducted a nested case-control study with 448 pancreatic cancer cases and their individually matched control subjects, based on the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to determine whether there was an altered pancreatic cancer risk associated with H. pylori infection and chronic corpus atrophic gastritis. Conditional logistic regression models were applied to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs), adjusted for matching factors and other potential confounders. Our results showed that pancreatic cancer risk was neither associated with H. pylori seropositivity (OR = 0.96; 95% CI: 0.70, 1.31) nor CagA seropositivity (OR = 1.07; 95% CI: 0.77, 1.48). We also did not find any excess risk among individuals seropositive for H. pylori but seronegative for CagA, compared with the group seronegative for both antibodies (OR = 0.94; 95% CI: 0.63, 1.38). However, we found that chronic corpus atrophic gastritis was non-significantly associated with an increased pancreatic cancer risk (OR = 1.35; 95% CI: 0.77, 2.37), and although based on small numbers, the excess risk was particularly marked among individuals seronegative for both H. pylori and CagA (OR = 5.66; 95% CI: 1.59, 20.19, p value for interaction < 0.01). Our findings provided evidence supporting the null association between H. pylori infection and pancreatic cancer risk in western European populations. However, the suggested association between chronic corpus atrophic gastritis and pancreatic cancer risk warrants independent verification in future studies, and, if confirmed, further studies on the underlying mechanisms.
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| 5. |
- Hughes, David J, et al.
(författare)
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Selenium status is associated with colorectal cancer risk in the European prospective investigation of cancer and nutrition cohort.
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:5, s. 1149-1161
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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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| 6. |
- Jakszyn, Paula, et al.
(författare)
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Hepcidin levels and gastric cancer risk in the EPIC-EurGast study
- 2017
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 141:5, s. 945-951
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Tidskriftsartikel (refereegranskat)abstract
- Hepcidin is the main regulator of iron homeostasis and dysregulation of proteins involved in iron metabolism has been associated with tumorogenesis. However, to date, no epidemiological study has researched the association between hepcidin levels and gastric cancer risk. To further investigate the relationship between hepcidin levels and gastric cancer risk, we conducted a nested case-control study (EURGAST) within the multicentric European Prospective Investigation into Cancer and Nutrition study. The study included 456 primary incident gastric adenocarcinoma cases and 900 matched controls that occurred during an average of 11 years of follow-up. We measured serum levels of hepcidin-25, iron, ferritin, transferrin and C-reactive protein. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of gastric cancer by hepcidin levels were estimated from multivariable conditional logistic regression models. Mediation effect of the ferritin levels on the hepcidin-gastric cancer pathway was also evaluated. After adjusting for relevant confounders, we observed a statistically significant inverse association between gastric cancer and hepcidin levels (OR 5 ng/l = 0.96, 95% CI = 0.93–0.99). No differences were found by tumor localization or histological type. In mediation analysis, we found that the direct effect of hepcidin only represents a nonsignificant 38% (95% CI: −69%, 91%). In summary, these data suggest that the inverse association of hepcidin levels and gastric cancer risk was mostly accounted by ferritin levels. Further investigation including repeated measures of hepcidin is needed to clarify their role in gastric carcinogenesis.
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| 7. |
- Murphy, Neil, et al.
(författare)
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A prospective evaluation of plasma polyphenol levels and colon cancer risk
- 2018
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 143:7, s. 1620-1631
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Tidskriftsartikel (refereegranskat)abstract
- Polyphenols have been shown to exert biological activity in experimental models of colon cancer; however, human data linking specific polyphenols to colon cancer is limited. We assessed the relationship between pre-diagnostic plasma polyphenols and colon cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Using high pressure liquid chromatography coupled to tandem mass spectrometry, we measured concentrations of 35 polyphenols in plasma from 809 incident colon cancer cases and 809 matched controls. We used multivariable adjusted conditional logistic regression models that included established colon cancer risk factors. The false discovery rate (qvalues ) was computed to control for multiple comparisons. All statistical tests were two-sided. After false discovery rate correction and in continuous log2 -transformed multivariable models, equol (odds ratio [OR] per log2 -value, 0.86, 95% confidence interval [95% CI] = 0.79-0.93; qvalue = 0.01) and homovanillic acid (OR per log2 -value, 1.46, 95% CI = 1.16-1.84; qvalue = 0.02) were associated with colon cancer risk. Comparing extreme fifths, equol concentrations were inversely associated with colon cancer risk (OR = 0.61, 95% CI = 0.41-0.91, ptrend = 0.003), while homovanillic acid concentrations were positively associated with colon cancer development (OR = 1.72, 95% CI = 1.17-2.53, ptrend < 0.0001). No heterogeneity for these associations was observed by sex and across other colon cancer risk factors. The remaining polyphenols were not associated with colon cancer risk. Higher equol concentrations were associated with lower risk, and higher homovanillic acid concentrations were associated with greater risk of colon cancer. These findings support a potential role for specific polyphenols in colon tumorigenesis.
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| 8. |
- Nimptsch, Katharina, et al.
(författare)
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Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk.
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:5, s. 1181-1192
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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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| 9. |
- Nimptsch, Katharina, et al.
(författare)
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Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 137:4, s. 911-920
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Tidskriftsartikel (refereegranskat)abstract
- Fetuin-A, also referred to as alpha 2-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 mg/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 mg/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.
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| 10. |
- Stepien, Magdalena, et al.
(författare)
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Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers : findings from a prospective cohort study
- 2016
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 138:2, s. 348-360
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Tidskriftsartikel (refereegranskat)abstract
- Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development.
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