| 1. |
- Aglago, Elom K., et al.
(author)
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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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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:1, s. 182-192
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Journal article (peer-reviewed)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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| 2. |
- Christakoudi, Sofia, et al.
(author)
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A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort
- 2023
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In: BMC Cancer. - 1471-2407. ; 23:1
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Journal article (peer-reviewed)abstract
- Background: Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). Methods: We evaluated body shape with the allometric “a body shape index” (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results: During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR = 0.984; 95% confidence interval: 0.961–1.007), we found borderline inverse associations for post-menopausal women (HR = 0.971; 0.942-1.000; n = 5268 cases) and breast cancers diagnosed at age ≥ 55 years (HR = 0.976; 0.951–1.002; n = 7043) and clear inverse associations for ER + PR- subtypes (HR = 0.894; 0.822–0.971; n = 726) and ER-PR- subtypes (HR = 0.906; 0.835–0.983 n = 759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR = 1.074; 1.049–1.098), for post-menopausal women (HR = 1.117; 1.085–1.150), for cancers diagnosed at age ≥ 55 years (HR = 1.104; 1.076–1.132), and for ER + PR + subtypes (HR = 1.122; 1.080–1.165; n = 3101), but not for PR- subtypes. Conclusions: In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases.
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| 3. |
- Clasen, Joanna L., et al.
(author)
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Reproductive and hormonal factors and risk of renal cell carcinoma among women in the european prospective investigation into cancer and nutrition
- 2023
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In: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 12:14, s. 15588-15600
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Journal article (peer-reviewed)abstract
- Background: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology.Materials & Methods: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.Results: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use.Conclusion: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.
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| 4. |
- Dainotti, Maria Giovanna, et al.
(author)
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Gamma-Ray Bursts as Distance Indicators by a Statistical Learning Approach
- 2024
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In: Astrophysical Journal Letters. - 2041-8205. ; 967:2
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Journal article (peer-reviewed)abstract
- Gamma-ray bursts (GRBs) can be probes of the early Universe, but currently, only 26% of GRBs observed by the Neil Gehrels Swift Observatory have known redshifts (z) due to observational limitations. To address this, we estimated the GRB redshift (distance) via a supervised statistical learning model that uses optical afterglow observed by Swift and ground-based telescopes. The inferred redshifts are strongly correlated (a Pearson coefficient of 0.93) with the observed redshifts, thus proving the reliability of this method. The inferred and observed redshifts allow us to estimate the number of GRBs occurring at a given redshift (GRB rate) to be 8.47-9 yr−1 Gpc−1 for 1.9 < z < 2.3. Since GRBs come from the collapse of massive stars, we compared this rate with the star formation rate, highlighting a discrepancy of a factor of 3 at z < 1.
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| 5. |
- Dainotti, Maria Giovanna, et al.
(author)
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On the Evolution of the Hubble Constant with the SNe Ia Pantheon Sample and Baryon Acoustic Oscillations : A Feasibility Study for GRB-Cosmology in 2030
- 2022
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In: Galaxies. - : MDPI AG. - 2075-4434. ; 10:1
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Journal article (peer-reviewed)abstract
- The difference from 4 to 6 σ in the Hubble constant (H0 ) between the values observed with the local (Cepheids and Supernovae Ia, SNe Ia) and the high-z probes (Cosmic Microwave Background obtained by the Planck data) still challenges the astrophysics and cosmology community. Previous analysis has shown that there is an evolution in the Hubble constant that scales as f (z) = H0/(1 + z)η, where H0 is H0 (z = 0) and η is the evolutionary parameter. Here, we investigate if this evolution still holds by using the SNe Ia gathered in the Pantheon sample and the Baryon Acoustic Oscillations. We assume H0 = 70 km s−1 Mpc−1 as the local value and divide the Pantheon into three bins ordered in increasing values of redshift. Similar to our previous analysis but varying two cosmological parameters contemporaneously (H0, Ω0m in the ΛCDM model and H0, wa in the w0waCDM model), for each bin we implement a Markov-Chain Monte Carlo analysis (MCMC) obtaining the value of H0 assuming Gaussian priors to restrict the parameters spaces to values we expect from our prior knowledge of the current cosmological models and to avoid phantom Dark Energy models with w < −1. Subsequently, the values of H0 are fitted with the model f (z). Our results show that a decreasing trend with η ∼ 10−2 is still visible in this sample. The η coefficient reaches zero in 2.0 σ for the ΛCDM model up to 5.8 σ for w0waCDM model. This trend, if not due to statistical fluctuations, could be explained through a hidden astrophysical bias, such as the effect of stretch evolution, or it requires new theoretical models, a possible proposition is the modified gravity theories, f (R). This analysis is meant to further cast light on the evolution of H0 and it does not specifically focus on constraining the other parameters. This work is also a preparatory to understand how the combined probes still show an evolution of the H0 by redshift and what is the current status of simulations on GRB cosmology to obtain the uncertainties on the Ω0m comparable with the ones achieved through SNe Ia.
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| 6. |
- Gibson, Spencer James, et al.
(author)
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Using Multivariate Imputation by Chained Equations to Predict Redshifts of Active Galactic Nuclei
- 2022
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In: Frontiers in Astronomy and Space Sciences. - : Frontiers Media SA. - 2296-987X. ; 9
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Journal article (peer-reviewed)abstract
- Redshift measurement of active galactic nuclei (AGNs) remains a time-consuming and challenging task, as it requires follow up spectroscopic observations and detailed analysis. Hence, there exists an urgent requirement for alternative redshift estimation techniques. The use of machine learning (ML) for this purpose has been growing over the last few years, primarily due to the availability of large-scale galactic surveys. However, due to observational errors, a significant fraction of these data sets often have missing entries, rendering that fraction unusable for ML regression applications. In this study, we demonstrate the performance of an imputation technique called Multivariate Imputation by Chained Equations (MICE), which rectifies the issue of missing data entries by imputing them using the available information in the catalog. We use the Fermi-LAT Fourth Data Release Catalog (4LAC) and impute 24% of the catalog. Subsequently, we follow the methodology described in Dainotti et al. (ApJ, 2021, 920, 118) and create an ML model for estimating the redshift of 4LAC AGNs. We present results which highlight positive impact of MICE imputation technique on the machine learning models performance and obtained redshift estimation accuracy.
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| 7. |
- Harewood, Rhea, et al.
(author)
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Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk : a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)
- 2024
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In: EBioMedicine. - : Elsevier. - 2352-3964. ; 101
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Journal article (peer-reviewed)abstract
- Background: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain.Methods: In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk.Findings: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47–0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59–0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer.Interpretation: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations. Funding: World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).
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| 8. |
- His, Mathilde, et al.
(author)
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Lifestyle correlates of eight breast cancer-related metabolites : a cross-sectional study within the EPIC cohort
- 2021
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In: BMC Medicine. - : BioMed Central. - 1741-7015. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: Metabolomics is a promising molecular tool for identifying novel etiological pathways leading to cancer. In an earlier prospective study among pre- and postmenopausal women not using exogenous hormones, we observed a higher risk of breast cancer associated with higher blood concentrations of one metabolite (acetylcarnitine) and a lower risk associated with higher blood concentrations of seven others (arginine, asparagine, phosphatidylcholines (PCs) aa C36:3, ae C34:2, ae C36:2, ae C36:3, and ae C38:2).Methods: To identify determinants of these breast cancer-related metabolites, we conducted a cross-sectional analysis to identify their lifestyle and anthropometric correlates in 2358 women, who were previously included as controls in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition cohort and not using exogenous hormones at blood collection. Associations of each metabolite concentration with 42 variables were assessed using linear regression models in a discovery set of 1572 participants. Significant associations were evaluated in a validation set (n = 786).Results: For the metabolites previously associated with a lower risk of breast cancer, concentrations of PCs ae C34:2, C36:2, C36:3, and C38:2 were negatively associated with adiposity and positively associated with total and saturated fat intakes. PC ae C36:2 was also negatively associated with alcohol consumption and positively associated with two scores reflecting adherence to a healthy lifestyle. Asparagine concentration was negatively associated with adiposity. Arginine and PC aa C36:3 concentrations were not associated to any of the factors examined. For the metabolite previously associated with a higher risk of breast cancer, acetylcarnitine, a positive association with age was observed.Conclusions: These associations may indicate possible mechanisms underlying associations between lifestyle and anthropometric factors, and risk of breast cancer. Further research is needed to identify potential non-lifestyle correlates of the metabolites investigated.
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| 9. |
- Jones, Geraint H., et al.
(author)
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The Comet Interceptor Mission
- 2024
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In: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
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Journal article (peer-reviewed)abstract
- Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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| 10. |
- Kliemann, Nathalie, et al.
(author)
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Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition
- 2021
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In: BMC Medicine. - : BioMed Central. - 1741-7015. ; 19:1
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Journal article (peer-reviewed)abstract
- Background: The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study.Methods: Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants.Results: After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR1-sd 1.50, 95% CI 1.30–1.74), WC (OR1-sd 1.46, 95% CI 1.27–1.69), and WHR (OR1-sd 1.54, 95% CI 1.33–1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR1-sd: 1.26, 95% CI 1.07–1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06–0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05–0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32–0.87, p = 0.01).Conclusions: Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.
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