90 research outputs found

    Μελέτη Μεντελιανής Τυχαιοποίησης για τη συσχέτιση διατροφικών χαρακτηριστικών με τον καρκίνο παχέος εντέρου

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    Εισαγωγή: Ο καρκίνος του παχέος εντέρου είναι ο τρίτος πιο διαδεδομένος καρκίνος παγκοσμίως απαριθμώντας πάνω από 1.2 εκατομμύρια νέες περιπτώσεις και 600.000 θανάτους ανά έτος. Ορισμένα χαρακτηριστικά σχετιζόμενα με τη διατροφή είναι γνωστοί παράγοντες κινδύνου για τον καρκίνο του παχέος εντέρου ενώ για την πλειοψηφία των διατροφικών παραγόντων, οι ενδείξεις ήταν είτε ασαφείς είτε περιορισμένες. Τα περισσότερα στοιχεία σχετικά με τη διατροφή και τον κίνδυνο ανάπτυξης καρκίνου προκύπτουν από μελέτες παρατήρησης. Σκοπός της παρούσας μελέτης είναι να ξεπεραστούν οι περιορισμοί αυτών των μελετών με τη χρήση της μεθόδου της Μενδελιανής τυχαιοποίησης. Εκτιμήθηκαν συσχετίσεις μεταξύ των γενετικά καθορισμένων προσλήψεων διατροφικών παραγόντων και του κινδύνου ανάπτυξης καρκίνου του παχέος εντέρου. Διεξήχθησαν αναλύσεις για τους ακόλουθους διατροφικούς παράγοντες: δημητριακά, φρέσκα φρούτα, επεξεργασμένο κρέας, πουλερικά, λιπαρά ψάρια, μη λιπαρά ψάρια, τυρί, τσάι και πράσινο τσάι. Μέθοδος: Πραγματοποιήθηκε μελέτη Μενδελιανής τυχαιοποίησης δύο δειγμάτων με τη χρήση περιληπτικών δεδομένων. Τα δεδομένα για τη σχέση των SNPs με τον καρκίνο του παχέος εντέρου αντλήθηκαν από 58,221 ασθενείς και 67,694 μάρτυρες από τη GECCO. Οι διατροφικοί παράγοντες επιλέχθηκαν από το World Cancer Research Fund (WCRF) Continuous Update Project (CUP) και τα περιληπτικά δεδομένα για τη σχέση τους με τα SNPs προήλθαν από GWAS της UK Biobank. Εφαρμόστηκε η μέθοδος Inverse Variance Weighted (IVW) για την εκτίμηση της αιτιακής σχέσης και πραγματοποιήθηκαν αναλύσεις ευαισθησίας (simple median, weighted median, MR-Egger, weighted mode, MR-PRESSO) για τον έλεγχο των παραδοχών της Μενδελιανής τυχαιοποίησης. Επιπρόσθετα, διεξήχθησαν αναλύσεις ανά υπότυπο του καρκίνου του παχέος εντέρου (κόλον, δεξί κόλον, αριστερό κόλον και ορθό). Αποτελέσματα: Η γενετικά καθορισμένη κατανάλωση λιπαρών ψαριών συσχετίστηκε με 27% χαμηλότερο κίνδυνο ανάπτυξης καρκίνου του παχέος εντέρου (Odds Ratio [OR]=0.73, 95% Διάστημα Εμπιστοσύνης [ΔΕ]=(0.58-0.92)), 30% χαμηλότερο κίνδυνο ανάπτυξης καρκίνου του κόλου (OR=0.70, 95% ΔΕ=(0.54-0.91)) και 37% χαμηλότερο κίνδυνο ανάπτυξης καρκίνου του αριστερού κόλου (OR=0.63, 95% ΔΕ=(0.46-0.85)). Επίσης, παρατηρήθηκε προστατευτική επίδραση της γενετικά καθορισμένης κατανάλωσης δημητριακών στον καρκίνου του ορθού (OR=0.59, 95% ΔΕ=(0.38-0.89)), ενώ οριακής στατιστικής σημαντικότητας προστατευτική συσχέτιση παρατηρήθηκε για τον ολικό καρκίνο παχέος εντέρου (OR=0.75, 95% ΔΕ=(0.55-1.01)). Προστατευτική επίδραση παρατηρήθηκε και για τη γενετικά καθορισμένη κατανάλωση φρέσκων φρούτων με τον καρκίνο του αριστερού κόλου (OR=0.58, 95% ΔΕ=(0.37-0.89)) χωρίς όμως να ενισχύεται από τις εκτιμήσεις των αναλύσεων ευαισθησίας. Δεν παρατηρήθηκε συσχέτιση των υπόλοιπων διατροφικών παραγόντων με τον καρκίνο του παχέος εντέρου. Συμπεράσματα: Τα ευρήματα έδειξαν πιθανή προστατευτική επίδραση των λιπαρών ψαριών στον ολικό καρκίνο του παχέος εντέρου, το ολικό κόλον και το αριστερό κόλον και ήπια προστατευτική των δημητριακών με τον ολικό καρκίνο του παχέος εντέρου και τον καρκίνο του ορθού. Παρόλα αυτά, δεν μπορούμε να αποφανθούμε με σιγουριά αιτιότητα λόγω πιθανής ύπαρξης πλειοτροπίας. Περαιτέρω μελέτες πρέπει να πραγματοποιηθούν στο μέλλον ώστε να επιβεβαιωθούν αυτά τα ευρήματα και να καταλήξουν σε στιβαρά αποτελέσματα.Background: Colorectal cancer is the third most common type of cancer worldwide with over one million new cases and 600,000 deaths each year. Several nutrition-related characteristics are well-established risk factors of colorectal cancer but for the vast majority of dietary factors the evidence was either inconclusive or limited. Most of the evidence regarding diet and risk of cancer occurrence emerges from observational studies. The aim of this study is to overcome their inherent limitations using the Mendelian randomization (MR) approach. Associations were estimated between genetically determined intakes of dietary factors and risk of colorectal cancer. We run analyses for the following dietary factors: cereals, fresh fruits, processed meat, poultry, oily fish, non-oily fish, cheese, tea and green tea. Methods: A two-sample MR study was conducted using summary data. Data for the association between the selected SNPs and risk of colorectal cancer were retrieved from 58,221 cases and 67,694 controls from GECCO. Diet factors were selected from World Cancer Research Fund (WCRF) Continuous Update Project (CUP) and summary data of their association with the SNPs stemmed from GWAS from the UK Biobank. Inverse Variance Weighted (IVW) method was implemented for the assessment of potential causality and sensitivity analyses (simple median, weighted median, MR-Egger weighted mode, MR-PRESSO) were performed to secure the non-violation of the MR assumptions. Subgroup analyses were conducted according to cancer anatomical distribution (colon, distal colon, proximal colon and rectal cancer). Results: One standard deviation (SD: highest vs lowest consumption) higher genetically determined consumption of oily fish was associated with a 27% (Odds Ratio [OR]= 0.73, 95% Confidence Interval [CI]=(0.58 -0.92), 30% (OR=0.70, 95% CI=0.54 -0.91)) and 37% (OR= 0.63, 95% CI=(0.46 -0.85)) lower risk of colorectal, colon and distal colon cancer, respectively. An inverse association was observed for a SD higher genetically determined consumption of cereals and rectal cancer (OR=0.59, 95% CI=(0.38-0.89)). A suggestive inverse association was observed for a SD higher genetically determined consumption of cereals with overall colorectal cancer (OR= 0.75, 95% CI=(0.55-1.01)). A suggestive inverse association was observed for a SD higher genetically determined consumption of fresh fruits with distal cancer (OR= 0.58, 95% CI=(0.37-0.89)) but was not robust to sensitivity analyses. There was no evidence that any of the other dietary factors were associated with colorectal cancer. Conclusions: There was an inverse association between oily fish and colorectal cancer, colon cancer and distal colon cancer. A suggestive inverse association was observed between cereals and both colorectal and rectal cancer. However, strong evidence cannot be proven due to potential pleiotropy. Further work is required to replicate and strengthen these findings

    Determination of the Oxidative Stress Biomarkers of 8-Hydroxydeoxyguanosine and Dityrosine in the Gills, Skin, Dorsal Fin, and Liver Tissue of Atlantic Salmon (Salmo salar) Parr

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    Oxidative stress is a condition caused by an imbalance in the occurrence of reactive oxygen species in the cells and tissues of organisms. An ultra-performance liquid chromatography–electrospray ionization tandem mass spectrometry (UPLC–ESI–MS/MS) method was developed for the simultaneous determination of two oxidative stress biomarkers, 8-hydroxydeoxyguanosine (8OHDG) and dityrosine (DIY), in the gills, skin, dorsal fin, and liver tissue of Atlantic salmon (Salmo salar) parr. The use of target analyte-specific 13C and 15N internal standards allowed quantification of each target analyte to be performed through the standard solvent calibration curve. The relative recoveries [mean ± (relative standard deviation%)] of 8OHDG and DIY were 101 ± 11 and 104 ± 13% at a fortified concentration of 10 ng/mL (8OHDG) and 500 ng/mL (DIY), respectively, ensuring the accuracy of the extraction and quantification. The chromatographic separation was carried out using a gradient elution program with a total run time of 5 min. The limits of detection (LODs) were 0.11 and 1.37 ng/g wet weight (w.w.) for 8OHDG and DIY, respectively. To demonstrate the applicability of the developed method, it was applied in 907 tissue samples that were collected from Atlantic salmon parr individuals reared in an experimental land-based recirculating aquaculture system (RAS) treated with peracetic acid. Moreover, the possibility of using the dorsal fin as an alternative matrix for the minimally invasive assessment of oxidative stress in Atlantic salmon parr was introduced. To our knowledge, 8OHDG and DIY were used for the first time as biomarkers for biomonitoring the fish health (oxidative stress) of Atlantic salmon parr in RAS.Determination of the Oxidative Stress Biomarkers of 8-Hydroxydeoxyguanosine and Dityrosine in the Gills, Skin, Dorsal Fin, and Liver Tissue of Atlantic Salmon (Salmo salar) ParrpublishedVersio

    Maternal bisphenol and phthalate urine concentrations and weight gain during pregnancy

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    Background: Insufficient or excessive gestational weight gain are associated with increased risks of adverse birth and childhood outcomes. Increasing evidence suggests that exposure to bisphenols and phthalates may disrupt hormonal pathways and thereby influence gestational weight gain. Objective: To examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with gestational weight gain. Methods: In a population-based prospective cohort study among 1,213 pregnant women, we measured early and mid-pregnancy bisphenol and phthalate urine concentrations. Maternal anthropometrics before pregnancy were obtained by questionnaire and repeatedly measure

    Rapid determination of thyroid hormones in blood plasma from Glaucous gulls and Baikal seals by HybridSPE®-LC-MS/MS

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    A rapid hybrid solid phase extraction (HybridSPE®) protocol tailored to liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) analysis, was developed for the determination of four thyroid hormones, L-Thyroxine (T4), 3,3′,5-triiodo-L-thyronine (T3), 3,3′,5′-triiodo-L-thyronine (rT3) and 3,3′-diiodo-L-thyronine (T2) in blood plasma from Glaucous gulls (Larus hyperboreus) and Baikal seals (Phoca sibirica). The use of target analyte specific 13C internal standards allowed quantification to be performed through the standard solvent calibration curves and alleviated the need to perform quantification with matrix match curves. The relative recoveries were 100.0–110.1 % for T4, 99.1–102.2 % for T3, 100.5–108.0 % for rT3, and 100.5–104.6 % for T2. The matrix effects ranged from −1.52 to −6.10 %, demonstrating minor signal suppression during analysis. The method intra-day precision (method repeatability, RSD %, N = 5, k = 1 day) and inter-day precision (method reproducibility, RSD %, N = 10, k = 2 days) at the 1 ng/mL concentration of fortification were 8.54–15.4 % and 15.4–24.8 %, respectively, indicating acceptable chromatographic peak stabilities for all target THs even at trace level concentrations. The method limit of detection (LOD) for T4, T3, rT3 and T2 was 0.17, 0.16, 0.30 and 0.17 ng/mL, respectively. The HybridSPE® protocol was simple and rapid (<1 min) upon application, while the HybridSPE® cartridge did not require (as in classical SPE cartridges) any additional equilibration nor conditioning step prior sample loading. A total of 46 blood plasma samples, 30 samples collected from Glaucous gulls and 16 samples collected from Baikal seals, were analyzed for thyroid hormones to demonstrate the applicability of the developed method in these wildlife species. The concentrations of T4 and T3 in blood plasma from the Glaucous gulls were 5.95–44.2 and 0.37–5.61 ng/mL, respectively, whereas those from Baikal seals were 3.57–46.5 and 0.45–2.07 ng/mL, respectively. In both species, rT3 demonstrated low detection rate, while T2 was not detected. Furthermore, cross-array comparison between the HybridSPE®-LC-MS/MS protocol and an established routine radioimmunoassay (RIA) kit-based method was performed for T4 and T3 concentrations from selected Baikal seal plasma samples.publishedVersio
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