| 1. |
- Aglago, Elom K., et al.
(författare)
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Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort
- 2020
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-3565 .- 1542-7714. ; 18:3, s. 6-666
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
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| 2. |
- Aglago, Elom K., et al.
(författare)
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Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk : A Case-Control Study Nested within a European Prospective Cohort
- 2021
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:1, s. 182-192
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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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| 3. |
- Barrdahl, Myrto, et al.
(författare)
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Post-G WAS gene-environment interplay in breast cancer : results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79 000 women
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:19, s. 5260-5270
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Tidskriftsartikel (refereegranskat)abstract
- We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (P-interaction = 8.84 x 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.
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| 4. |
- Campa, Daniele, et al.
(författare)
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Leukocyte telomere length in relation to pancreatic cancer risk: a prospective study.
- 2014
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Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 23:11, s. 2447-2454
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk, the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting. Methods: we measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). Results: We observed that the mean LTL was higher in cases (0.59±0.20) than in controls (0.57±0.17), although this difference was not statistically significant (p=0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-Peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk , OR=1.13 (1.01-1.27). Additional analyses by cubic spline regression suggested a possible non-linear relationship between RTL and pancreatic cancer risk (P=0.022), with a statistically non-significant increase in risk at very low LTL, as well as a significant increase at high LTL. Conclusion: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer. Impact: The results of this manuscript can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk.
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| 5. |
- Duarte-Salles, Talita, et al.
(författare)
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Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population
- 2016
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Ingår i: Cancer Prevention Research. - 1940-6207 .- 1940-6215. ; 9:9, s. 758-765
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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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| 6. |
- Fasanelli, Francesca, et al.
(författare)
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Hypomethylation of smoking-related genes is associated with future lung cancer in four prospective cohorts
- 2015
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- DNA hypomethylation in certain genes is associated with tobacco exposure but it is unknown whether these methylation changes translate into increased lung cancer risk. In an epigenome-wide study of DNA from pre-diagnostic blood samples from 132 case–control pairs in the NOWAC cohort, we observe that the most significant associations with lung cancer risk are for cg05575921 in AHRR (OR for 1 s.d.=0.37, 95% CI: 0.31–0.54, P-value=3.3 × 10−11) and cg03636183 in F2RL3 (OR for 1 s.d.=0.40, 95% CI: 0.31–0.56, P-value=3.9 × 10−10), previously shown to be strongly hypomethylated in smokers. These associations remain significant after adjustment for smoking and are confirmed in additional 664 case–control pairs tightly matched for smoking from the MCCS, NSHDS and EPIC HD cohorts. The replication and mediation analyses suggest that residual confounding is unlikely to explain the observed associations and that hypomethylation of these CpG sites may mediate the effect of tobacco on lung cancer risk.
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| 7. |
- Fedirko, Veronika, et al.
(författare)
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Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma : a nested case-control study
- 2017
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 72:15
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking.METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression.RESULTS: = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses.CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.
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| 8. |
- Gasull, Magda, et al.
(författare)
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Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort
- 2019
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 169, s. 417-433
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases.OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles.METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models.RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quantified 16 of the 22 POPs in more than 90% of individuals. All 22 POPs were detected in some participants, and the smallest number of POPs detected in one person was 15 (median, 19) with few differences by country. The highest concentrations were found for p,p'-DDE, PCBs 153 and 180 (median concentration: 3371, 1023, and 810 pg/mL, respectively). We assessed the possible occurrence of disease progression bias (DPB) in eight situations defined by lipid and POP measurements, on one hand, and by four factors: interval from blood draw to index date, tumour subsite, tumour stage, and grade of differentiation, on the other. In seven of the eight situations results supported the absence of DPB.CONCLUSIONS: The coexistence of differences across study centres in some design features and participant characteristics is of relevance to other multicentre studies. Relationships among subjects' characteristics and among such characteristics and design features may play important roles in the forthcoming analyses on the association between plasma concentrations of POPs and pancreatic cancer risk.
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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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