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1.
JAMA ; 331(22): 1910-1917, 2024 06 11.
Article in English | MEDLINE | ID: mdl-38583868

ABSTRACT

Importance: Randomized clinical trials of cancer screening typically use cancer-specific mortality as the primary end point. The incidence of stage III-IV cancer is a potential alternative end point that may accelerate completion of randomized clinical trials of cancer screening. Objective: To compare cancer-specific mortality with stage III-IV cancer as end points in randomized clinical trials of cancer screening. Design, Setting, and Participants: This meta-analysis included 41 randomized clinical trials of cancer screening conducted in Europe, North America, and Asia published through February 19, 2024. Data extracted included numbers of participants, cancer diagnoses, and cancer deaths in the intervention and comparison groups. For each clinical trial, the effect of screening was calculated as the percentage reduction between the intervention and comparison groups in the incidence of participants with cancer-specific mortality and stage III-IV cancer. Exposures: Randomization to a cancer screening test or to a comparison group in a clinical trial of cancer screening. Main Outcomes and Measures: End points of cancer-specific mortality and incidence of stage III-IV cancer were compared using Pearson correlation coefficients with 95% CIs, linear regression, and fixed-effects meta-analysis. Results: The included randomized clinical trials tested benefits of screening for breast (n = 6), colorectal (n = 11), lung (n = 12), ovarian (n = 4), prostate (n = 4), and other cancers (n = 4). Correlation between reductions in cancer-specific mortality and stage III-IV cancer varied by cancer type (I2 = 65%; P = .02). Correlation was highest for trials that screened for ovarian (Pearson ρ = 0.99 [95% CI, 0.51-1.00]) and lung (Pearson ρ = 0.92 [95% CI, 0.72-0.98]) cancers, moderate for breast cancer (Pearson ρ = 0.70 [95% CI, -0.26 to 0.96]), and weak for colorectal (Pearson ρ = 0.39 [95% CI, -0.27 to 0.80]) and prostate (Pearson ρ = -0.69 [95% CI, -0.99 to 0.81]) cancers. Slopes from linear regression were estimated as 1.15 for ovarian cancer, 0.75 for lung cancer, 0.40 for colorectal cancer, 0.28 for breast cancer, and -3.58 for prostate cancer, suggesting that a given magnitude of reduction in incidence of stage III-IV cancer produced different magnitudes of change in incidence of cancer-specific mortality (P for heterogeneity = .004). Conclusions and Relevance: In randomized clinical trials of cancer screening, incidence of late-stage cancer may be a suitable alternative end point to cancer-specific mortality for some cancer types, but is not suitable for others. These results have implications for clinical trials of multicancer screening tests.


Subject(s)
Early Detection of Cancer , Neoplasm Staging , Neoplasms , Randomized Controlled Trials as Topic , Female , Humans , Male , Endpoint Determination , Incidence , Neoplasms/mortality , Neoplasms/pathology , Prostatic Neoplasms/mortality , Prostatic Neoplasms/diagnosis
2.
J Natl Cancer Inst ; 115(9): 1050-1059, 2023 09 07.
Article in English | MEDLINE | ID: mdl-37260165

ABSTRACT

BACKGROUND: We sought to develop a proteomics-based risk model for lung cancer and evaluate its risk-discriminatory performance in comparison with a smoking-based risk model (PLCOm2012) and a commercially available autoantibody biomarker test. METHODS: We designed a case-control study nested in 6 prospective cohorts, including 624 lung cancer participants who donated blood samples at most 3 years prior to lung cancer diagnosis and 624 smoking-matched cancer free participants who were assayed for 302 proteins. We used 470 case-control pairs from 4 cohorts to select proteins and train a protein-based risk model. We subsequently used 154 case-control pairs from 2 cohorts to compare the risk-discriminatory performance of the protein-based model with that of the Early Cancer Detection Test (EarlyCDT)-Lung and the PLCOm2012 model using receiver operating characteristics analysis and by estimating models' sensitivity. All tests were 2-sided. RESULTS: The area under the curve for the protein-based risk model in the validation sample was 0.75 (95% confidence interval [CI] = 0.70 to 0.81) compared with 0.64 (95% CI = 0.57 to 0.70) for the PLCOm2012 model (Pdifference = .001). The EarlyCDT-Lung had a sensitivity of 14% (95% CI = 8.2% to 19%) and a specificity of 86% (95% CI = 81% to 92%) for incident lung cancer. At the same specificity of 86%, the sensitivity for the protein-based risk model was estimated at 49% (95% CI = 41% to 57%) and 30% (95% CI = 23% to 37%) for the PLCOm2012 model. CONCLUSION: Circulating proteins showed promise in predicting incident lung cancer and outperformed a standard risk prediction model and the commercialized EarlyCDT-Lung.


Subject(s)
Lung Neoplasms , Proteomics , Humans , Risk Assessment , Case-Control Studies , Prospective Studies , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung , Early Detection of Cancer
3.
Int J Food Sci Nutr ; 73(4): 552-563, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34965361

ABSTRACT

The purpose of this study was to explore the possible association between dairy and NCDs and identify possible dairy types that could lower the odds of NCDs. Data were from the 2003-2016 NHANES, a cross-sectional study with 20,297 adults. Multivariable logistic regression analyses and restricted cubic spline (RCS) models were conducted. In the highest intake group (>250 g/d, 1 daily serving), yogurt and milk were inversely associated with the odds of general obesity and central obesity [OR (95% CI), general obesity, 0.74 (0.60-0.91) and 0.75 (0.68-0.83); central obesity, 0.70 (0.56-0.87), and 0.77 (0.70-0.86), respectively, p < 0.05]. Higher milk intake is inversely associated with diabetes, and higher cream intake is associated with a lower likelihood of hyperlipidaemia. The intake of yogurt, milk, cheese, and butter was 0-308 g/d (0-1.2 daily servings), 0-887 g/d (0-3.5 daily servings), <75 g/d (1.7 daily servings), and <15 g/d (0.5 daily servings), respectively.


Subject(s)
Dairy Products , Noncommunicable Diseases , Adult , Animals , Cross-Sectional Studies , Diet , Humans , Milk , Nutrition Surveys , Obesity, Abdominal , Yogurt
4.
Aging (Albany NY) ; 13(15): 19835-19866, 2021 08 10.
Article in English | MEDLINE | ID: mdl-34375305

ABSTRACT

BACKGROUND: We assessed the effect of bisphosphonates (BPs) on breast cancer (BCa) patient survival and explored how long the effect can persist after treatment. METHODS: We performed a meta-analysis and trial sequential analysis (TSA) of prospective studies including randomized controlled trials (RCTs) and cohort studies. We performed extensive sensitivity analyses to assess the robustness of the findings. RESULTS: Seventeen RCTs and eight cohorts with 81508 BCa patients were identified. A significant beneficial effect of BPs on BCa survival was found (RR, 0.725; 95% CI, 0.627-0.839), and the TSA results also suggested firm evidence for this beneficial effect. Both summarized results from RCTs and cohorts provided firm evidence for this effect, although the effect estimates were stronger from cohorts than RCTs (RR, 0.892; 95% CI, 0.829-0.961; 0.570; 95% CI, 0.436-0.745; respectively). This beneficial effect was confirmed for bone-metastases (RR, 0.713; 95% CI, 0.602-0.843) and postmenopausal women (RR, 0.737; 95% CI, 0.640-0.850). Importantly, our results demonstrated that this beneficial effect was retained at least 1-2 years after treatment completion (RR, 0.780; 95% CI, 0.638-0.954) and could persist for up to more than 4 years after treatment completion (RR, 0.906; 95% CI, 0.832-0.987). Extensive sensitivity analyses showed the robustness of our results. The GRADE quality of evidence was generally judged to be moderate to high. CONCLUSIONS: The present study provides firm evidence for a significant beneficial effect of BPs on BCa survival in patients with early-stage BCa, and this effect was retained at least 1-2 years after BP treatment completion.


Subject(s)
Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Breast Neoplasms/mortality , Diphosphonates/therapeutic use , Bone Neoplasms/mortality , Epidemiologic Studies , Female , Humans , Prospective Studies , Randomized Controlled Trials as Topic , Time Factors
5.
Front Oncol ; 11: 629860, 2021.
Article in English | MEDLINE | ID: mdl-34178621

ABSTRACT

BACKGROUND: Aberrant DNA methylation is a critical regulator of gene expression and plays a crucial role in the occurrence, progression, and prognosis of colorectal cancer (CRC). We aimed to identify methylation-driven genes by integrative epigenetic and transcriptomic analysis to predict the prognosis of CRC patients. METHODS: Methylation-driven genes were selected for CRC using a MethylMix algorithm and LASSO regression screening strategy, and were further used to construct a prognostic risk-assessment model. The Cancer Genome Atlas (TCGA) database was obtained as the training set for both the screening of methylation-driven genes and the effect of genes signature on CRC prognosis. Then, the prognostic genes signature was validated in three independent expression arrays of CRC data from Gene Expression Omnibus (GEO). RESULTS: We identified 143 methylation-driven genes, of which the combination of BATF, PHYHIPL, RBP1, and PNPLA4 expression levels was screened as a better prognostic model with the best area under the curve (AUC) (AUC = 0.876). Compared with patients in the low-risk group, CRC patients in the high-risk group had significantly poorer overall survival in the training set (HR = 2.184, 95% CI: 1.404-3.396, P < 0.001). Similar results were observed in the validation set. Moreover, VanderWeele's mediation analysis indicated that the effect of methylation on prognosis was mediated by the levels of their expression (HRindirect = 1.473, P = 0.001, Proportion mediated, 69.10%). CONCLUSIONS: We identified a four-gene prognostic signature by integrative analysis and developed a risk-assessment model that is significantly associated with patients' survival. Methylation-driven genes might be a potential prognostic signature for CRC patients.

6.
Aging (Albany NY) ; 13(7): 10112-10127, 2021 03 26.
Article in English | MEDLINE | ID: mdl-33819180

ABSTRACT

Diet quality fluctuates throughout one's adulthood, yet it remains unclear how long-term diet quality changes are related to type 2 diabetes mellitus (T2DM) and its biomarkers. We aimed to examine the association of long-term diet quality with T2DM and its biomarkers. Diet quality was assessed by the revised DBI-07, in which diet quality distance levels (DQD) represented the overall diet quality. Participants were clustered into classes sharing similar DQD levels using latent class mixed model. We used Cox regression and random effect linear regression to assess DQD trajectories' association with T2DM and its biomarkers. Three DQD trajectories were derived: moderate to gradual decrease, high to moderate, high stable DQD level representing 2.14%, 6.18% and, 91.68% of the population. Compared to class 1, class 2 and 3 were associated with an increased risk of T2DM [HR=4.40; 95%CI: 2.02-9.59]; [HR=3.68; 95% CI: 2.11-6.43]. When class 3 was used as a reference, class 1 was also associated with an increased risk of TDM [HR=2.71; 95%CI: 1.55-4.73]. Our findings suggest that a long-term unhealthy diet is associated with an increased risk of T2DM. Gradually reducing DQD level may not make a difference, which establishes the importance of promoting healthy eating habits at early adulthood.


Subject(s)
Diabetes Mellitus, Type 2/blood , Diet , Feeding Behavior/physiology , Adult , Biomarkers/blood , Female , Humans , Male , Middle Aged , Risk Factors
7.
Aging (Albany NY) ; 12(20): 20561-20586, 2020 10 28.
Article in English | MEDLINE | ID: mdl-33113509

ABSTRACT

Homogenous DNA methylation clearly affects clinical outcomes. However, less is known about the effects of heterogeneous methylation. We aimed to investigate the different effects between CASK promoter methylation heterogeneity and homogeneity on colorectal cancer (CRC) patients' prognosis. The methylation status of CASK in 296 tumor tissues and 255 adjacent normal tissues were evaluated using Methylation-sensitive high-resolution melting (MS-HRM). Digital MS-HRM (dMS-HRM) visualized heterogeneous methylation and subsequent sequencing provided exact patterns. Log-rank test and Cox regression model were adopted to assess the association between CASK methylation status and CRC prognosis with propensity score (PS) method to control confounding biases. Heterogeneous methylation was detected in both tumor (52.2%) and non-neoplastic tissue surrounding the tumor (62.4%). It occurred more frequently in lower levels of tumor invasion (P = 0.002) and male patients (P < 0.001). Compared with heterogeneous methylation, patients with CASK homogeneous methylation presented poorer overall survival (OS) (HR: 1.919, 95% CI: 1.146-3.212, P = 0.013) and disease-free survival (DFS) (HR: 1.913, 95% CI: 1.146-3.194, P = 0.013). This unfavorable effect still existed among older (≥ 50), Dukes staging C/D, and rectal cancer patients. MS-HRM and dMS-HRM when combined can assess the degree and complexity of heterogeneous methylation with a visible pattern.


Subject(s)
Colorectal Neoplasms/genetics , DNA Methylation , Guanylate Kinases/genetics , Colorectal Neoplasms/mortality , DNA Methylation/physiology , Female , Humans , Male , Middle Aged , Prognosis , Survival Rate
8.
J Am Heart Assoc ; 9(19): e016804, 2020 10 20.
Article in English | MEDLINE | ID: mdl-32975166

ABSTRACT

Background Nonpharmacologic interventions that modify lifestyle can lower blood pressure (BP) and have been assessed in numerous randomized controlled trials and pairwise meta-analyses. It is still unclear which intervention would be most efficacious. Methods and Results Bayesian network meta-analyses were performed to estimate the comparative effectiveness of different interventions for lowering BP. From 60 166 potentially relevant articles, 120 eligible articles (14 923 participants) with a median follow-up of 12 weeks, assessing 22 nonpharmacologic interventions, were included. According to the surface under the cumulative ranking probabilities and Grading of Recommendations Assessment, Development and Evaluation (GRADE) quality of evidence, for adults with prehypertension to established hypertension, high-quality evidence indicated that the Dietary Approach to Stop Hypertension (DASH) was superior to usual care and all other nonpharmacologic interventions in lowering systolic BP (weighted mean difference, 6.97 mm Hg; 95% credible interval, 4.50-9.47) and diastolic BP (weighted mean difference, 3.54 mm Hg; 95% credible interval, 1.80-5.28). Compared with usual care, moderate- to high-quality evidence indicated that aerobic exercise, isometric training, low-sodium and high-potassium salt, comprehensive lifestyle modification, breathing-control, and meditation could lower systolic BP and diastolic BP. For patients with hypertension, moderate- to high-quality evidence suggested that the interventions listed (except comprehensive lifestyle modification) were associated with greater systolic BP and diastolic BP reduction than usual care; salt restriction was also effective in lowering both systolic BP and diastolic BP. Among overweight and obese participants, low-calorie diet and low-calorie diet plus exercise could lower more BP than exercise. Conclusions DASH might be the most effective intervention in lowering BP for adults with prehypertension to established hypertension. Aerobic exercise, isometric training, low-sodium and high-potassium salt, comprehensive lifestyle modification, salt restriction, breathing-control, meditation and low-calorie diet also have obvious effects on BP reduction.


Subject(s)
Diet Therapy/methods , Diet, Sodium-Restricted/methods , Exercise , Hypertension , Prehypertension , Risk Reduction Behavior , Comparative Effectiveness Research , Exercise/physiology , Exercise/psychology , Humans , Hypertension/diagnosis , Hypertension/physiopathology , Hypertension/psychology , Hypertension/therapy , Prehypertension/physiopathology , Prehypertension/psychology , Prehypertension/therapy
9.
Cancer Sci ; 111(12): 4558-4566, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32970347

ABSTRACT

Diagnostic markers for both colorectal cancer (CRC) and its precursor lesions are lacking. Although aberrant methylation of the secretin receptor (SCTR) gene was observed in CRC, the diagnostic performance has not been evaluated. Therefore, this study aimed to assess and verify the diagnostic value of SCTR methylation of CRC and its precursor lesions through integrating the largest methylation data. The diagnostic performance of SCTR methylation was analyzed in the discovery set from The Cancer Genome Atlas (TCGA) CRC methylation data (N = 440), and verified in a large-scale test set (N = 938) from the Gene Expression Omnibus (GEO). Targeted bisulfite sequencing analysis was developed and applied to detect the methylation status of SCTR in our independent validation set (N = 374). Our findings revealed that the SCTR gene was frequently hypermethylated at its CpG islands in CRC. In the TCGA discovery set, the diagnostic score was constructed using 4 CpG sites (cg01013590, cg20505223, cg07176264, and cg26009192) and achieved high diagnostic performance (area under the ROC curve [AUC] = 0.964). In the GEO test set, the diagnostic score had robust diagnostic ability to distinguish CRC (AUC = 0.948) and its precursor lesions (AUC = 0.954) from normal samples. Moreover, hypermethylation of the SCTR gene was also found in cell-free DNA samples collected from CRC patients, but not in those from healthy controls. In the validation set, consistent results were observed using the targeted bisulfite sequencing array. Our study highlights that hypermethylation at CpG islands of the SCTR gene is a potential diagnostic biomarker in CRCs and its precursor lesions.


Subject(s)
Biomarkers, Tumor/metabolism , Colorectal Neoplasms/metabolism , Receptors, G-Protein-Coupled/metabolism , Receptors, Gastrointestinal Hormone/metabolism , Biomarkers, Tumor/genetics , Cell-Free Nucleic Acids , Colorectal Neoplasms/diagnosis , CpG Islands , Gene Expression , Humans , Leukocytes/metabolism , Methylation , Protein Array Analysis , Receptors, G-Protein-Coupled/genetics , Receptors, Gastrointestinal Hormone/genetics , Reproducibility of Results , Sensitivity and Specificity
10.
BMC Cancer ; 20(1): 692, 2020 Jul 25.
Article in English | MEDLINE | ID: mdl-32711505

ABSTRACT

BACKGROUND: Differential DNA methylation panel derived from peripheral blood could serve as biomarkers of CRC susceptibility. However, most of the previous studies utilized post-diagnostic blood DNA which may be markers of disease rather than susceptibility. In addition, only a few studies have evaluated the predictive potential of differential DNA methylation in CRC in a prospective cohort and on a genome-wide basis. The aim of this study was to identify a potential panel of DNA methylation biomarkers in peripheral blood that is associated with CRC risk and therefore serve as epigenetic biomarkers of disease susceptibility. METHODS: DNA methylation profile of a nested case-control study with 166 CRC and 424 healthy normal subjects were obtained from the Gene Expression Omnibus (GEO) database. The differentially methylated markers were identified by moderated t-statistics. The DNA methylation panel was constructed by stepwise logistic regression and the least absolute shrinkage and selection operator in the training dataset. A methylation risk score (MRS) model was constructed and the association between MRS and CRC risk assessed. RESULTS: We identified 48 differentially methylated CpGs sites, of which 33 were hypomethylated. Of these, sixteen-CpG based MRS that was associated with CRC risk (OR = 2.68, 95% CI: 2.13, 3.38, P <  0.0001) was constructed. This association is confirmed in the testing dataset (OR = 2.02, 95% CI: 1.48, 2.74, P <  0.0001) and persisted in both males and females, younger and older subjects, short and long time-to-diagnosis. The MRS also predicted CRC with AUC 0.82 (95% CI: 0.76, 0.88), indicating high accuracy. CONCLUSIONS: Our study has identified a novel DNA methylation panel that is associated with CRC and could, if validated be useful for the prediction of CRC risk in the future.


Subject(s)
Colorectal Neoplasms/genetics , CpG Islands , DNA Methylation , Genetic Predisposition to Disease , Area Under Curve , Case-Control Studies , Female , Genetic Markers , Humans , Logistic Models , Male , Middle Aged , Predictive Value of Tests , Risk Factors
11.
Int J Food Sci Nutr ; 71(8): 979-990, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32233701

ABSTRACT

The purpose of this study was to investigate the association between refined grains intake and obesity in China. Refined grain intake was considered in relation to energy intake and at varied levels of macronutrient distribution. A cross-sectional study of 6913 participants was conducted using internet-based dietary questionnaire for Chinese (IDQC). The associations and dose-response relationships between refined grains intake and obesity were investigated using multivariable logistic regression analyses and restricted cubic spline (RCS) models. There was a positive association between refined grains intake and abdominal obesity for all participants (forth quartile OR, 1.313; 95% CI, 1.103-1.760; p < .05) and this association persisted in low energy, low carbohydrate, high fat and high protein level subgroups. A range of favourable refined grains intake was 88-116 g/d (3-4 servings/d), which might decrease the likelihood of obesity for Chinese residents. Further prospective studies are needed to confirm these findings.


Subject(s)
Diet, High-Fat/adverse effects , Diet, High-Protein/adverse effects , Dietary Carbohydrates/adverse effects , Edible Grain , Energy Intake , Obesity, Abdominal/drug therapy , Adolescent , Adult , Aged , Asian People , China/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Nutrients , Young Adult
12.
BMC Cancer ; 20(1): 200, 2020 Mar 12.
Article in English | MEDLINE | ID: mdl-32164586

ABSTRACT

BACKGROUND: Existing data from several reports on the association between lipid profile and ovarian tumour (OT) suggests divergent conclusions. Our aim was to examine whether circulating lipid profile: total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) differed between cases and non-cases of OT. METHODS: Electronic repositories; PUBMED, EMBASE and Cochrane library were explored through December 2019 to retrieve published articles for inclusion in the meta-analysis after quality assessment. Heterogeneity was assessed using I2 statistics, the effect of individual studies on the overall effect size was tested using sensitivity analysis and funnel plot was used to evaluate publication bias. RESULTS: Twelve studies, involving 1767 OT cases and 229,167 non-cases of OT were included in this meta-analysis and I2 statistics ranged between 97 and 99%. Mean circulating TC (- 16.60 [- 32.43, - 0.77]mg/dL; P = 0.04) and HDL (- 0.25[- 0.43, - 0.08]mmol/L; P = 0.005) were significantly lower among OT cases compared to non-OT cases. CONCLUSION: Decreased TC and HDL profiles were observed among subjects with OT in this collection of reports. The implications of TC and HDL in tumour manifestations and growth need to be validated in a large multi-ethnic longitudinal cohort adjusting for relevant confounders.


Subject(s)
Lipoproteins, HDL/blood , Ovarian Neoplasms/blood , Triglycerides/blood , Cholesterol/blood , Female , Humans , Lipoproteins, LDL/blood , Male , Risk Factors
13.
Aging (Albany NY) ; 11(23): 11640-11658, 2019 12 13.
Article in English | MEDLINE | ID: mdl-31834866

ABSTRACT

The early diagnosis and accurate prognosis prediction of esophageal cancer is an essential part of improving survival. However, these diseases lack effective and specific markers. A total of 1,744 samples of HumanMethylation450 data were integrated to identify and validate specific methylation markers for esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) as well as for Barrett's esophagus (BE) using The Cancer Genome Atlas and the Gene Expression Omnibus. The diagnostic and prognostic methylation classifiers were constructed by moderated t-statistics and the least absolute shrinkage and selection operator method. The diagnostic methylation classifier using 12 CpG sites was constructed in training set (377 samples) that could effectively discriminate samples of BE, EAC, and ESCC from normal tissue (AUC = 0.992), which achieved highly predictive ability in both internal (187 samples, AUC = 0.990) and external validation (184 samples, AUC = 0.978). The prognostic methylation classifier with 3 CpG and 2 CpG sites for EAC and ESCC respectively, could accurately estimate the prognosis of an individual patient and improved the predictive ability of the tumor node metastasis staging system. Overall, our study systematically analyzed large-scale methylation data and provided promising markers for the diagnosis and prognosis of esophageal cancer.


Subject(s)
Biomarkers, Tumor , Databases, Genetic , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/metabolism , Genome, Human , DNA Methylation , Humans , Prognosis
14.
Endocr Connect ; 8(7): 979-987, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31176300

ABSTRACT

According to its incidence patterns, colorectal cancer (CRC) tends to occur more frequently in males than in females, and the evidence shows that CRC is a hormone-related tumor. These findings indicate that androgen receptor (AR) gene methylation might be important for the regulation of the CRC risk in the different sexes. We used a case-control study to investigate the association between AR methylation in peripheral blood (PBL) and CRC risk. A cohort study was conducted to analyze the effect of AR methylation levels in both PBL and tissue on the prognosis of CRC. AR methylation levels were detected using methylation-sensitive high-resolution melting (MS-HRM). The results indicate that the hypomethylation of AR was significantly associated with the risk of CRC (OR = 1.869, 95% CI: 1.629-2.141, P < 0.001), and the results remained similar after adjusting for the propensity score (PS) (OR = 1.344, 95% CI: 1.147-1.575, P < 0.001) and PS matching (OR = 1.138, 95% CI: 1.000-1.292 P = 0.049). The hypomethylation of AR was significantly associated with CRC in males (OR = 2.309, 95% CI: 1.200-4.245; P = 0.012) but not females (OR = 1.000, 95% CI: 0.567-1.765; P = 0.999). The methylation status of AR in PBL and tissue does not seem to be associated with prognosis in colorectal cancer (OR = 1.425, 95% CI: 0.895-2.269, P = 0.135; OR = 0.930, 95% CI: 0.674-1.285, P = 0.661). We conclude that AR hypomethylation in PBL is associated with a high risk of CRC and may serve as a biomarker. Further studies involving large sample sizes are needed to validate the results of this study.

15.
Am J Clin Nutr ; 109(6): 1611-1619, 2019 06 01.
Article in English | MEDLINE | ID: mdl-31136662

ABSTRACT

BACKGROUND: Because consumption of conventional yogurt has beneficial effects in a healthy population, and insulin resistance (IR) is the mutual pathogenesis in nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS), we hypothesized that yogurt would ameliorate IR in patients with NAFLD and MetS. OBJECTIVES: The aim of this study was to investigate the effects of yogurt on IR and secondary endpoints including liver fat, gut microbiota, and serum biomarkers of inflammation and oxidative stress in obese women with NAFLD and MetS. METHODS: One hundred obese women aged 36-66 y with both NAFLD and MetS were randomly assigned to consume 220 g/d of either conventional yogurt or milk for 24 wk. At baseline and week 24, we measured anthropometric indices, serum glucose, insulin, lipids, and cytokines in all participants, and liver fat and gut microbiota in 20 participants randomly selected from each group. RESULTS: Forty-eight participants from the yogurt group and 44 from the milk group completed the intervention. Compared with milk, yogurt significantly decreased the homeostasis model assessment of insulin resistance (-0.53; 95% CI: -1.03, -0.02), fasting insulin (-2.77 mU/L; 95% CI: -4.91, -0.63 mU/L), 2-h insulin (-25.5 mU/L; 95% CI: -33.0, -17.9 mU/L), 2-h area under the curve for insulin (-29.4 mU/L · h; 95% CI: -44.0, -14.8 mU/L · h), alanine aminotransferase (-4.65 U/L; 95% CI: -8.67, -0.64 U/L), intrahepatic lipid (-3.44%; 95% CI: -6.19%, -0.68%), and hepatic fat fraction (-3.48%; 95% CI: -6.34%, -0.63%). Yogurt also decreased serum LPS (-0.31 EU/mL; 95% CI: -0.48, -0.14 EU/mL), fibroblast growth factor 21 (-57.76 pg/mL; 95% CI: -86.32, -29.19 pg/mL), lipids, and biomarkers of inflammation and oxidative stress, and altered gut microbiota composition. Mediation analysis showed that yogurt may improve IR by reducing serum lipids, inflammation, oxidative stress, and LPS. CONCLUSIONS: Yogurt was better than milk at ameliorating IR and liver fat in obese Chinese women with NAFLD and MetS, possibly by improving lipid metabolism, reducing inflammation, oxidative stress, and LPS, and changing the gut microbiota composition. This trial was registered at www.chictr.org.cn as ChiCTR-IPR-15006801.


Subject(s)
Fats/metabolism , Insulin Resistance , Liver/metabolism , Non-alcoholic Fatty Liver Disease/diet therapy , Obesity/diet therapy , Yogurt/analysis , Adult , Aged , Female , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/metabolism , Gastrointestinal Microbiome , Humans , Male , Metabolic Syndrome , Middle Aged , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/microbiology , Obesity/metabolism , Oxidative Stress
16.
Acta Diabetol ; 56(2): 187-195, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30413881

ABSTRACT

AIM: To assess whether oral branched-chain amino acids (BCAA) supplementation exerts influence on circulating BCAA and the significance of dietary BCAA in type 2 diabetes and obesity risk. METHOD: We searched PUBMED, EMBASE and Cochrane library through June 2018 to retrieve and screen published reports for inclusion in the meta-analysis after methodological assessment. Heterogeneity of studies was evaluated using I2 statistics, while sensitivity analysis and funnel plot were used to evaluate the potential effect of individual studies on the overall estimates and publication bias, respectively, using RevMan 5.3. RESULT: Eight articles on randomized clinical trial of oral BCAA supplementation, and seven articles on dietary BCAA intake and type 2 diabetes/obesity risks were eligible for inclusion in our meta-analyses. Mean difference and 95% confidence interval (CI) of circulating leucine was 39.65 (3.54, 75.76) µmol/L, P = 0.03 post-BCAA supplementation. Also, OR and 95% CI for higher total BCAA intake and metabolic disorder risks were, 1.32 (1.14, 1.53), P = 0.0003-type 2 diabetes and 0.62 (0.47, 0.82), P = 0.0008-obesity. CONCLUSION: Oral BCAA supplementation exerts modest influence on circulating leucine profile and higher total BCAA intake is positively and contra-positively associated with type 2 diabetes and obesity risk, respectively.


Subject(s)
Amino Acids, Branched-Chain/pharmacology , Diabetes Mellitus, Type 2 , Obesity , Diabetes Mellitus, Type 2/diet therapy , Diabetes Mellitus, Type 2/metabolism , Dietary Supplements , Humans , Obesity/diet therapy , Obesity/metabolism
17.
Malariaworld J ; 7: 9, 2016.
Article in English | MEDLINE | ID: mdl-38601354

ABSTRACT

Background: In or der to combat the bur den of malaria, different strategies, including Insecticide Treated Nets (ITNs), have been put in place. ITNs have been distributed with support from international donors and this necessitates an increase in monitoring and evaluation efforts in order to determine ITN impact as well as prioritise future programmes. The current standard for estimating impact indicators of ITNs are household surveys. These, however, are expensive and not conducted frequently. Collecting information from school children has been found to be a cheap and fast means for routine monitoring and evaluation of malaria control programmes in sub-Saharan Africa. This study was conducted to explore school children's report of household ownership and use of ITNs in Oyo State, Nigeria. Materials and methods: A cross-sectional survey was conducted. A three-stage sampling technique was used to select 611 pupils from 15 out of 88 primary schools. Information on pupils' socio-demographics, report of household ownership and use of ITNs were obtained using a semi-structured interviewer-administered questionnaire. Data was analysed using descriptive statistics and Chi-square tests at 5% level of significance. Results: Respondents' mean age was 10.5±1.7 yrs; 52.7% were females, 84.6% were Yoruba and 65.3% lived with children below 5 yrs of age in their households. Most of the respondents (81.7%) reported household ownership of at least one ITN. The majority (76.4%) obtained nets through mass distribution campaigns. Most of the respondents (89%) reported use of ITNs by a household member the night preceding the survey. More than half of the respondents (51.6%) reported ITN use by children below 5 yrs of age. Class was significantly associated with reported household ownership of ITNs (χ2= 9.217, p <0.010). Conclusion: The majority of the pupils reported household ownership and use of ITNs. They should be consider ed a potential source of information in monitoring and evaluation activities related to ITN ownership and use.

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