| 1. |
- Aleksandrova, Krasimira, et al.
(författare)
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A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk
- 2015
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 107:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. Methods: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. Results: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P-difference = .87) and after excluding case patients diagnosed within the first four follow-up years. Conclusions: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
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| 2. |
- Aleksandrova, Krasimira, et al.
(författare)
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Physical activity, mediating factors and risk of colon cancer : insights into adiposity and circulating biomarkers from the EPIC cohort
- 2017
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Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 46:6, s. 1823-1835
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Tidskriftsartikel (refereegranskat)abstract
- There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer. We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003. A total of 713 incident colon cancer cases were matched, using risk-set sampling, to 713 controls on age, sex, study centre, fasting status and hormonal therapy use. The amount of total physical activity during the past year was expressed in metabolic equivalent of task [MET]-h/week. Anthropometric measurements and blood samples were collected at study baseline. High physical activity was associated with a lower risk of colon cancer: relative risk a parts per thousand91 MET-h/week vs < 91 MET-h/week = 0.75 [95% confidence interval (CI): 0.57 to 0.96]. In mediation analyses, this association was accounted for by waist circumference: proportion explained effect (PEE) = 17%; CI: 4% to 52%; and the biomarkers soluble leptin receptor (sOB-R): PEE = 15%; 95% CI: 1% to 50% and 5-hydroxyvitamin D (25[OH]D): PEE = 30%; 95% CI: 12% to 88%. In combination, these factors explained 45% (95% CI: 20% to 125%) of the association. Beyond waist circumference, sOB-R and 25[OH]D additionally explained 10% (95% CI: 1%; 56%) and 23% (95% CI: 6%; 111%) of the association, respectively. Promoting physical activity, particularly outdoors, and maintaining metabolic health and adequate vitamin D levels could represent a promising strategy for colon cancer prevention.
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| 3. |
- 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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| 4. |
- Anantharaman, Devasena, et al.
(författare)
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Combined effects of smoking and HPV16 in oropharyngeal cancer
- 2016
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 45:3, s. 752-761
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although smoking and HPV infection are recognized as important risk factors for oropharyngeal cancer, how their joint exposure impacts on oropharyngeal cancer risk is unclear. Specifically, whether smoking confers any additional risk to HPV-positive oropharyngeal cancer is not understood.Methods: Using HPV serology as a marker of HPV-related cancer, we examined the interaction between smoking and HPV16 in 459 oropharyngeal (and 1445 oral cavity and laryngeal) cancer patients and 3024 control participants from two large European multicentre studies. Odds ratios and credible intervals [CrI], adjusted for potential confounders, were estimated using Bayesian logistic regression.Results: Both smoking [odds ratio (OR [CrI]: 6.82 [4.52, 10.29]) and HPV seropositivity (OR [CrI]: 235.69 [99.95, 555.74]) were independently associated with oropharyngeal cancer. The joint association of smoking and HPV seropositivity was consistent with that expected on the additive scale (synergy index [CrI]: 1.32 [0.51, 3.45]), suggesting they act as independent risk factors for oropharyngeal cancer.Conclusions: Smoking was consistently associated with increase in oropharyngeal cancer risk in models stratified by HPV16 seropositivity. In addition, we report that the prevalence of oropharyngeal cancer increases with smoking for both HPV16-positive and HPV16-negative persons. The impact of smoking on HPV16-positive oropharyngeal cancer highlights the continued need for smoking cessation programmes for primary prevention of head and neck cancer.
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| 5. |
- Bakker, Marije F., et al.
(författare)
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Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort
- 2016
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 103:2, s. 454-464
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.Objective: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.Design: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin, retinol, alpha-tocopherol, gamma-tocopherol, and 454 vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.Results: In quintile 5 compared with quintile 1, alpha-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and beta-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for beta-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).Conclusion: Our results indicate that higher concentrations of plasma beta-carotene and alpha-carotene are associated with lower breast cancer risk of ER tumors.
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| 6. |
- Besevic, Jelena, et al.
(författare)
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Reproductive factors and epithelial ovarian cancer survival in the EPIC cohort study
- 2015
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 113:11, s. 1622-1631
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reproductive factors influence the risk of developing epithelial ovarian cancer (EOC), but little is known about their association with survival. We tested whether prediagnostic reproductive factors influenced EOC-specific survival among 1025 invasive EOC cases identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, which included 521 330 total participants (approximately 370 000 women) aged 25-70 years at recruitment from 1992 to 2000. Methods: Information on reproductive characteristics was collected at recruitment. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), and multivariable models were adjusted for age and year of diagnosis, body mass index, tumour stage, smoking status and stratified by study centre. Results: After a mean follow-up of 3.6 years (+/- 3.2 s.d.) following EOC diagnosis, 511 (49.9%) of the 1025 women died from EOC. We observed a suggestive survival advantage in menopausal hormone therapy (MHT) users (ever vs never use, HR = 0.80, 95% CI = 0.62-1.03) and a significant survival benefit in long-term MHT users (>= 5 years use vs never use, HR = 0.70, 95% CI = 0.50-0.99, P-trend = 0.04). We observed similar results for MHT use when restricting to serous cases. Other reproductive factors, including parity, breastfeeding, oral contraceptive use and age at menarche or menopause, were not associated with EOC-specific mortality risk. Conclusions: Further studies are warranted to investigate the possible improvement in EOC survival in MHT users.
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| 7. |
- Carayol, Marion, et al.
(författare)
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Blood Metabolic Signatures of Body Mass Index : A Targeted Metabolomics Study in the EPIC Cohort
- 2017
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 16:9, s. 3137-3146
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomics is now widely used to characterize metabolic phenotypes associated with lifestyle risk factors such as obesity. The objective of the present study was to explore the associations of body mass index (BMI) with 145 metabolites measured in blood samples in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolites were measured in blood from 392 men from the Oxford (UK) cohort (EPIC-Oxford) and in 327 control subjects who were part of a nested case-control study on hepatobiliary carcinomas (EPIC-Hepatobiliary). Measured metabolites included amino acids, acylcarnitines, hexoses, biogenic amines, phosphatidylcholines, and sphingomyelins. Linear regression models controlled for potential confounders and multiple testing were run to evaluate the associations of metabolite concentrations with BMI. 40 and 45 individual metabolites showed significant differences according to BMI variations, in the EPIC-Oxford and EPIC-Hepatobiliary subcohorts, respectively. Twenty two individual metabolites (kynurenine, one sphingomyelin, glutamate and 19 phosphatidylcholines) were associated with BMI in both subcohorts. The present findings provide additional knowledge on blood metabolic signatures of BMI in European adults, which may help identify mechanisms mediating the relationship of BMI with obesity-related diseases.
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| 8. |
- Chuang, Shu-Chun, et al.
(författare)
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Cellular immune activity biomarker neopterin is associated hyperlipidemia : results from a large population-based study
- 2016
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Ingår i: Immunity & Ageing. - : Springer Science and Business Media LLC. - 1742-4933. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Increased serum neopterin had been described in older age two decades ago. Neopterin is a biomarker of systemic adaptive immune activation that could be potentially implicated in metabolic syndrome (MetS). Measurements of waist circumference, triglycerides, high-density lipoprotein cholesterol (HDLC), systolic and diastolic blood pressure, glycated hemoglobin as components of MetS definition, and plasma total neopterin concentrations were performed in 594 participants recruited in the European Prospective Investigation into Cancer and Nutrition (EPIC).Results: Higher total neopterin concentrations were associated with reduced HDLC (9.7 %, p < 0.01 for men and 9.2 %, p < 0.01 for women), whereas no association was observed with the rest of the MetS components as well as with MetS overall (per 10 nmol/L: OR = 1.42, 95 % CI = 0.85-2.39 for men and OR = 1.38, 95 % CI = 0.79-2.43).Conclusions: These data suggest that high total neopterin concentrations are cross-sectionally associated with reduced HDLC, but not with overall MetS.
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| 9. |
- Cramer, Daniel W., et al.
(författare)
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Anti-CA15.3 and Anti-CA125 Antibodies and ovarian cancer risk : Results from the EPIC cohort
- 2018
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Ingår i: Cancer Epidemiology Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 27:7, s. 790-804
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neoplastic and non-neoplastic events may raise levels of mucins, CA15.3, and CA125, and generate antibodies against them, but their impact on epithelial ovarian cancer (EOC) risk has not been fully defined. Methods: CA15.3, CA125, and IgG1 antibodies against them were measured in 806 women who developed EOC and 1,927 matched controls from the European Prospective Investigation of Nutrition and Cancer. Associations between epidemiologic factors and anti-mucin antibodies were evaluated using generalized linear models; EOC risks associated with anti-mucin antibodies, by themselves or in combination with respective antigens, were evaluated using conditional logistic regression. Results: In controls, lower antibodies against both mucins were associated with current smoking; and, in postmenopausal women, higher levels with longer oral contraceptive use and later-age-at and shorter-interval-since last birth. Lower anti-CA15.3 antibodies were associated with higher body mass and, in premenopausal women, more ovulatory cycles. Higher anti-CA15.3 and anti-CA125 antibodies were associated with higher risk for mucinous EOC occurring ≥ 3 years from enrollment. Long-term risk for serous EOC was reduced in women with low CA125 and high anti-CA125 antibodies relative to women with low concentrations of both. Conclusions: We found general support for the hypothesis that anti-mucin antibody levels correlate with risk factors for EOC. Antibodies alone or in combinations with their antigen may predict longer term risk of specific EOC types. Impact: Anti-CA125 and anti-CA15.3 antibodies alone or in perspective of antigens may be informative in the pathogenesis of EOC subtypes, but less useful for informing risk for all EOC.
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| 10. |
- 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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