Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 387
Filtrar
1.
J Thorac Oncol ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33137463

RESUMO

RATIONALE: The workup and longitudinal monitoring for subjects presenting with pulmonary nodules is a pressing clinical problem. A blood-based biomarker panel potentially has utility for identifying subjects at higher risk for harboring a malignant nodule for whom additional work-up would be indicated or subjects at reduced risk for whom imaging based follow-up would be indicated. OBJECTIVES: To assess whether a previously described four-protein biomarker panel, previously reported to improve assessment of lung cancer risk compared to a smoking-based lung cancer risk model, can provide discrimination between benign and malignant indeterminate pulmonary nodules. METHODS: A previously validated multiplex enzyme linked immunoassay was performed on matched case and control samples from each cohort. MEASUREMENTS: The biomarker panel was tested in two case-control cohorts of patients presenting with indeterminate pulmonary nodules at the University of Pittsburgh Medical Center and The University of Texas Southwestern. MAIN RESULTS: In both cohorts, the biomarker panel resulted in improved prediction of lung cancer risk over a model based on nodule size alone. Of particular note, the addition of the marker panel to nodule size greatly improved sensitivity at a high specificity in both cohorts. CONCLUSIONS: A four-marker biomarker panel, previously validated to improve lung cancer risk prediction, also shows utility in distinguishing benign from malignant indeterminate pulmonary nodules. Its performance in improving sensitivity at a high specificity indicates potential utility of the marker panel in assessing likelihood of malignancy in otherwise indeterminate nodules.

2.
Int J Cancer ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33210298

RESUMO

2,456 lung cancer cases and 5,342 controls were evaluated in this International Lung Cancer Consortium (ILCCO) pooled analysis on estrogen-related hormonal factors and lung cancer in Asian women. Random effect of study site and fixed effect of age, smoking status, comprehensive smoking index, and family history of lung cancer were adjusted for in the multivariable logistic regression models. We found that late onset of menarche conferred elevated odds of lung cancer with adjusted odds ratio (OR) of 1.24 (95% confidence interval, CI=1.05 , 1.45) for 17 years or older, compared with 14 years or younger. Late onset of menopause at 55 years old or older was associated with lung cancer with OR=1.24 (95% CI=1.02 , 1.51). Non-natural menopause was associated with an OR of 1.39 (95%CI=1.13 , 1.71). More live births showed reversed association with lung cancer (ORs of 5 or more live births: 0.71 (95%CI=0.60 , 0.84), compared with 0-2 live births (Ptrend <0.001). A later first child delivery seemed associated with an increased susceptibility: OR of 21-25 years old: 1.23 (95% CI=1.06 , 1.40), 26 or older: 1.27 (95%CI=1.06, 1.52), Ptrend =0.010). Oral contraceptives use appeared to be protective with an OR of 0.69 (95% CI=0.57, 0.83). Stronger for adenocarcinoma than squamous cell carcinoma, these relationships were not clearly modified by smoking status, probably because of lower prevalence of smoking. This is a first and largest pooling study of lung cancer among Asian women and the results suggested potential roles of hormone-related pathways in the etiology of this disease. This article is protected by copyright. All rights reserved.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33203693

RESUMO

BACKGROUND: Interleukin-27 mRNA is highly enriched in the tissue of hepatocellular carcinoma. Overexpression of interleukin-27 gene has been found to increase T cell expression of inhibitory receptors, an immunosuppressive feature in tumor microenvironment, that promotes the development of hepatocellular carcinoma. METHODS: Two parallel case-control studies of hepatocellular carcinoma, each with 100 case-control pairs were conducted in the Singapore Chinese Health Study and the Shanghai Cohort Study to examine the association between serum interleukin-27 levels and risk of developing hepatocellular carcinoma. The interleukin-27 concentrations were significantly elevated in sera collected from study participants 4-5 years prior to the diagnosis of hepatocellular carcinoma in both cohort studies. RESULTS: Compared with the lowest tertile of interleukin-27, odds ratios (ORs)of hepatocellular carcinoma for the highest tertile of interleukin-27 was 46.08 [95% confidence interval (CI): 4.68-453.86] in the Singapore Chinese Health Study and 19.09 (95% CI: 3.81-95.57) in the Shanghai Cohort Study (both ptrend <0.001). The corresponding ORs in both cohort studies were 42.47 (95% CI: 8.30-217.40) among individuals negative for hepatitis B surface antigen (HBsAg) and 242.46 (95% IC: 38.42-1529.01) among those positive for HBsAg compared with the lowest tertile of interleukin-27 and negative HBsAg. CONCLUSION: Levels of interleukin-27 in prediagnostic sera were significantly associated with increased risk of hepatocellular carcinoma development. IMPACT: Interleukin-27 through its immunosuppressive property may play a significant role in the development of hepatocellular carcinoma. Serum levels of interleukin-27 may be used as a biomarker for prediction of hepatocellular carcinoma development.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33187965

RESUMO

BACKGROUND: While the associations between individual lifestyle factors and risk of hepatocellular carcinoma (HCC) have been previously described, their combined impact on HCC risk is unknown. METHODS: The association of a composite score of healthy lifestyle factors, including body mass index, alcohol consumption, cigarette smoking, alternative Mediterranean diet, and sleep duration, and HCC risk was examined in the Singapore Chinese Health Study, an on-going prospective cohort study of 63,257 Chinese. Cox proportional hazard regression method was used to estimate hazard ratio (HR) and its 95% confidence interval (CI). Conditional logistic regression method was used to evaluate this composite lifestyle score-HCC risk association among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody. RESULTS: After a mean follow-up of 17.7 years, 561 participants developed HCC. Individuals with higher composite scores representing healthier lifestyles (range 0-8) were at significantly lower risk of HCC. Compared to the lowest composite score category (0-4), the HRs (95% CIs) for the composite scores of 5, 6, 7, and 8 were 0.67 (0.62-0.85), 0.61 (0.48-0.77), 0.49 (0.37-0.65), and 0.13 (0.06-0.30), respectively (Ptrend<0.0001). A similar inverse association was observed in participants with negative HBsAg and anti-HCV negative serology (HR=0.38, 95% CI: 0.19-0.79; for the highest versus the lowest category of the composite scores (Ptrend=0.001). CONCLUSION: Healthy lifestyles protects against HCC development, especially for individuals without hepatitis B virus and hepatitis C infections. IMPACT: Our current study highlight the importance of a comprehensive lifestyle modification strategy for HCC primary prevention.

5.
J Am Med Dir Assoc ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33218913

RESUMO

OBJECTIVE: To examine the associations between dietary patterns in midlife and likelihood of future healthy ageing in Chinese older adults. DESIGN: Prospective population-based study. SETTING AND PARTICIPANTS: We included 14,159 participants aged 45-74 years who were free from cancer, cardiovascular disease, or diabetes at baseline (1993-1998) from the Singapore Chinese Health Study. METHODS: Dietary intakes in midlife were assessed by a validated food frequency questionnaire at baseline. Diet quality was scored according to the alternate Mediterranean diet (aMED), the Dietary Approaches to Stop Hypertension (DASH) diet, the alternative Healthy Eating Index (AHEI)-2010, overall plant-based diet index (PDI), and healthful plant-based diet index (hPDI). Healthy ageing was assessed at the third follow-up visit (2014-2016), which occurred about 20 years after the baseline visit, and was defined as the absence of 10 chronic diseases, no impairment of cognitive function, no limitations in instrumental activities of daily living, no clinical depression at screening, good overall self-perceived health, good physical functioning, and no function-limiting pain among participants who had survival to at least 65 years of age. Multivariable-adjusted logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each dietary pattern score and healthy ageing. RESULTS: About 20.0% of participants met the healthy ageing criteria. The OR (95% CI) for healthy ageing comparing the highest with the lowest quartile of diet quality scores was 1.52 (1.31-1.77) for aMED, 1.53 (1.35-1.73) for DASH, 1.39 (1.23-1.57) for AHEI-2010, 1.34 (1.18-1.53) for PDI, and 1.45 (1.27-1.65) for hPDI (all P-trend < .001). Each standard deviation increment in different diet quality scores was associated with 12% to 18% higher likelihood of healthy ageing. CONCLUSIONS AND IMPLICATIONS: In this Chinese population, adherence to various healthy dietary patterns at midlife is associated with higher likelihood of healthy ageing at later life.

6.
Int J Cancer ; 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129230

RESUMO

There is limited research on the effect of dietary quality on hepatocellular carcinoma (HCC) risk in populations with relatively high risk of HCC. Using data from Singapore Chinese Health Study, a prospective cohort study, of 63 257 Chinese aged 45 to 74, we assessed four diet-quality index (DQI) scores: the Alternative Health Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH) and Heathy Diet Indicator (HDI). We identified 561 incident HCC cases among the cohort participants after a mean of 17.6 years of follow-up. Cox proportional hazard regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for HCC in relation to these DQI scores. Unconditional logistic regression method was used to evaluate the associations between DQIs and HCC risk among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg). High scores of AHEI-2010, aMED and DASH, representing higher dietary quality, were associated with lower risk of HCC (all Ptrend < .05). Compared with the lowest quartile, HRs (95% CIs) of HCC for the highest quartile of AHEI-2010, aMED and DASH were 0.69 (0.53-0.89), 0.70 (0.52-0.95) and 0.67 (0.51-0.87), respectively. No significant association between HDI and HCC risk was observed. Among HBsAg-negative individuals, similar inverse associations were observed, and the strongest inverse association was for aMED (HRQ4vsQ1 = 0.46, 95% CI: 0.23-0.94, Ptrend = .10). These findings support the notion that adherence to a healthier diet may lower the risk of HCC, suggesting that dietary modification may be an effective approach for primary prevention of HCC.

7.
Nutr J ; 19(1): 119, 2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126880

RESUMO

BACKGROUND: Shorter telomere length (TL) has been associated with poor health behaviors, increased risks of chronic diseases and early mortality. Excessive shortening of telomere is a marker of accelerated aging and can be influenced by oxidative stress and nutritional deficiency. Plasma n6:n3 polyunsaturated fatty acid (PUFA) ratio may impact cell aging. Increased dietary intake of marine n-3 PUFA is associated with reduced telomere attrition. However, the effect of plasma PUFA on leukocyte telomere length (LTL) and its interaction with genetic variants are not well established. METHODS: A nested coronary artery disease (CAD) case-control study comprising 711 cases and 638 controls was conducted within the Singapore Chinese Health Study (SCHS). Samples genotyped with the Illumina ZhongHua-8 array. Plasma n-3 and n-6 PUFA were quantified using mass spectrometry (MS). LTL was measured with quantitative PCR method. Linear regression was used to test the association between PUFA and LTL. The interaction between plasma PUFAs and genetic variants was assessed by introducing an additional term (PUFA×genetic variant) in the regression model. Analysis was carried out in cases and controls separately and subsequently meta-analyzed using the inverse-variance weighted method. We further assessed the association of PUFA and LTL with CAD risk by Cox Proportional-Hazards model and whether the effect of PUFA on CAD was mediated through LTL by using structural equation modeling. RESULTS: Higher n6:n3 ratio was significantly associated with shorter LTL (p = 0.018) and increased CAD risk (p = 0.005). These associations were mainly driven by elevated plasma total n-3 PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (p < 0.05). There was a statistically significant interaction for an intergenic single nucleotide polymorphism (SNP) rs529143 with plasma total n-3 PUFA and DHA on LTL beyond the genome-wide threshold (p < 5 ×  10- 8). Mediation analysis showed that PUFA and LTL affected CAD risk independently. CONCLUSIONS: Higher plasma n6:n3 PUFA ratio, and lower EPA and DHA n-3 PUFAs were associated with shorter LTL and increased CAD risk in this Chinese population. Furthermore, genetic variants may modify the effect of PUFAs on LTL. PUFA and LTL had independent effect on CAD risk in our study population.

8.
J Phys Chem B ; 124(44): 9829-9839, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33104345

RESUMO

The thermodynamics and kinetics of protein folding and protein aggregation in vivo are of great importance in numerous scientific areas including fundamental biophysics research, nanotechnology, and medicine. However, these processes remain poorly understood in both in vivo and in vitro systems. Here we extend an established model for protein aggregation that is based on the kinetic equations for the moments of the polymer size distribution by introducing macromolecular crowding particles into the model using scaled-particle and transition-state theories. The model predicts that the presence of crowders can either speed up, cause no change to, or slow down the progress of the aggregation compared to crowder-free solutions, in striking agreement with experimental results from nine different amyloid-forming proteins that utilized dextran as the crowder. These different dynamic effects of macromolecular crowding can be understood in terms of the change of excluded volume associated with each reaction step.

9.
Front Immunol ; 11: 2027, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013860

RESUMO

Pleural effusions, when benign, are attributed to cardiac events and suffusion of fluid within the pleural space. When malignant, lymphatic obstruction by tumor and failure to absorb constitutively produced fluid is the predominant formulation. The prevailing view has been challenged recently, namely that the lymphatics are only passive vessels, carrying antigenic fluid to secondary lymphoid sites. Rather, lymphatic vessels can be a selective barrier, efficiently coordinating egress of immune cells and factors within tissues, limiting tumor spread and immune pathology. An alternative explanation, offered here, is that damage associated molecular pattern molecules, released in excess, maintain a local milieu associated with recruitment and retention of immune cells associated with failed lymphatic clearance and functional lymphatic obstruction. We found that levels of high mobility group box 1 (HMGB1) were equally elevated in both benign and malignant pleural effusions (MPEs) and that limited diversity of T cell receptor expressing gamma and delta chain were inversely associated with these levels in MPEs. Acellular fluid from MPEs enhanced γδ T cell proliferation in vitro, while inhibiting cytokine production from γδ T cells and monocytes as well as restricting monocyte chemotaxis. Novel therapeutic strategies, targeting HMGB1 and its neutralization in such effusions as well as direct delivery of immune cells into the pleural space to reconstitute normal physiology should be considered.

10.
Zhongguo Gu Shang ; 33(10): 970-4, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33107263

RESUMO

OBJECTIVE: To investigate therapeutic effect of minimally invasive percutaneous plate internal fixation (MIPPO) through a single incision in treating open distal tibiofibula fractures. METHODS: From March 2015 to February 2019, 10 patients with open distal tibiofibula fractures were treated with MIPPO technique through single anterolateral incision, including 8 males and 2 females, aged from 31 to 68 years old. According to Gustilo classification, 6 patients were typeⅠ, 3 patients were typeⅡand 1 patient was type ⅢA. Operative time, intraoperative blood loss and fracture healing were observed, Mazur ankle joint scoring was used to evaluate clinical effect. RESULTS: All patients were followed up from 9 to 24 months. Operative time ranged from 85 to 120 min, intraoperative blood loss ranged from 80 to 200 ml, fracture healing time ranged from 18 to 30 weeks. Nine patients with Gustilo typeⅠandⅡachieved satisfactory healing wound, original wound of 1 patient with Gustilo type ⅢA was poor, and healed by skin flap transplantation at stageⅡ. No steel exposed and infection occurred. According to Mazur ankle scoring at the final following-up, total score was from 61 to 97, and 8 patients got excellent result, 1 good and 1 poor. CONCLUSION: MIPPO technique through anterolateral single incision for the treatment of open distal tibiofibula fractures could protect original medial wound in opertaion, avoid plate exposed through anterolateral extensor tendon to cover internal fixation, and MIPPO technique could protect fracture end blood flow to improve fracture healing rate, and it is a kind of choice.


Assuntos
Placas Ósseas , Fraturas Expostas , Adulto , Idoso , Feminino , Fixação Interna de Fraturas , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos
11.
Artigo em Inglês | MEDLINE | ID: mdl-33045076

RESUMO

BACKGROUND: Telomere attrition has been proposed as a hallmark of ageing. We previously reported on the association between blood leukocyte telomere length (LTL) at mid-life and risk of chronic diseases and mortality. METHODS: In this study, we investigated the effect of mid-life LTL and genetic proxies on five markers of ageing outcomes, namely handgrip strength, timed up-and-go (TUG), Singapore-modified Mini-Mental State Examination (SM-MMSE) scores, anxiety, and depression indices, measured after a median 20-year follow-up in the Singapore Chinese Health Study (N = 9,581). RESULTS: We observed a significant association between mid-life LTL and handgrip strength later in life (P = 0.004, Padjust = 0.020), as well as a nominal significant association between mid-life LTL and TUG later in life (P = 0.036, Padjust = 0.180). The weighted Genetic Risk Score (wGRS) comprising 15 previously reported LTL reducing loci in East-Asians was not significantly associated with handgrip strength. However, results from Structural Equation Modeling (SEM) showed that the effect of this wGRS on handgrip strength was mediated through LTL (proportion of wGRS effect on handgrip strength mediated through LTL = 33.3%, P = 0.010). CONCLUSIONS: Longer mid-life LTL was associated with increased handgrip strength later in life.

12.
Genet Epidemiol ; 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32924180

RESUMO

Clinical trial results have recently demonstrated that inhibiting inflammation by targeting the interleukin-1ß pathway can offer a significant reduction in lung cancer incidence and mortality, highlighting a pressing and unmet need to understand the benefits of inflammation-focused lung cancer therapies at the genetic level. While numerous genome-wide association studies (GWAS) have explored the genetic etiology of lung cancer, there remains a large gap between the type of information that may be gleaned from an association study and the depth of understanding necessary to explain and drive translational findings. Thus, in this study we jointly model and integrate extensive multiomics data sources, utilizing a total of 40 genome-wide functional annotations that augment previously published results from the International Lung Cancer Consortium (ILCCO) GWAS, to prioritize and characterize single nucleotide polymorphisms (SNPs) that increase risk of squamous cell lung cancer through the inflammatory and immune responses. Our work bridges the gap between correlative analysis and translational follow-up research, refining GWAS association measures in an interpretable and systematic manner. In particular, reanalysis of the ILCCO data highlights the impact of highly associated SNPs from nuclear factor-κB signaling pathway genes as well as major histocompatibility complex mediated variation in immune responses. One consequence of prioritizing likely functional SNPs is the pruning of variants that might be selected for follow-up work by over an order of magnitude, from potentially tens of thousands to hundreds. The strategies we introduce provide informative and interpretable approaches for incorporating extensive genome-wide annotation data in analysis of genetic association studies.

13.
Mol Genet Genomic Med ; : e1450, 2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32794371

RESUMO

BACKGROUND: Haptoglobin (Hp) is a plasma protein with strong anti-inflammation and antioxidant activities. Its plasma level is known to be inversely associated with many inflammatory diseases, including cardiovascular diseases. However, the association of HP genetic variants with coronary artery disease (CAD) severity/mortality, and how they interact with common CAD risk factors are largely unknown. METHODS: We conducted the analysis in a Singaporean Chinese CAD population with Gensini severity scores (N = 582) and subsequently evaluated the significant findings in an independent cohort with cardiovascular mortality (excluding stroke) as outcome (917 cases and 19,093 controls). CAD risk factors were ascertained from questionnaires, and stenosis information from medical records. Mortality was identified through linkage with the nationwide registry of births and deaths in Singapore. Linear regression analysis between HP genetic variant (rs217181) and disease outcome were performed. Interaction analyses were performed by introducing an interaction term in the same regression models. RESULTS: Although rs217181 was not significantly associated with CAD severity and cardiovascular mortality (excluding stroke) in all subjects, when stratified by hypertension status, hypertensive individuals with the minor T allele have more severe CAD (ß = 0.073, SE = 0.030, p = 0.015) and non-hypertensive individuals with the T allele have lower risk for mortality (odds ratio = 0.771 (0.607-0.980), p = 0.033). CONCLUSION: HP genetic variant is not associated with CAD severity and mortality in the general population. However, hypertensive individuals with the rs217181 T allele associated with higher Hp levels had more severe CAD while non-hypertensive individuals with the same allele had lower risk for mortality in the Chinese population.

14.
Mov Disord ; 35(10): 1765-1773, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32643256

RESUMO

BACKGROUND: Despite experimental evidence implicating oxidative stress in the pathogenesis of PD, epidemiological studies have provided inconsistent associations between dietary antioxidants and risk of developing PD. Furthermore, no study has been done in any Asian population. OBJECTIVES: We examined the associations for intake levels of dietary carotenoids (α-carotene, ß-carotene, lycopene, ß-cryptoxanthin, and lutein) and vitamins (vitamin A, C and E) and the risk of developing PD. METHODS: We used data from the Singapore Chinese Health Study, a population-based prospective cohort of 63,257 men and women aged 45 to 74 years during enrollment in 1993-1998. Antioxidant intake was derived from a validated semiquantitative food frequency questionnaire. Incident cases were identified through follow-up interviews, hospital records, or PD registries through 31 July 2018. Hazard ratios and corresponding 95% confidence intervals were derived from multivariable Cox proportional hazard regression models with adjustment for other lifestyle and dietary factors. RESULTS: During an average 19.4 years of follow-up, 544 incident PD cases were identified. No association was found for dietary carotenoids, individually or summed. Hazard ratio comparing highest to lowest quartile for total carotenoids was 0.98 (95% confidence interval: 0.76-1.28; Ptrend = 0.83). There were also no clear dose-dependent associations of dietary vitamins A, C, and E with risk of developing PD (all Ptrend ≥ 0.10). Sensitive analyses with lag time and excluding supplement use did not materially alter results. CONCLUSIONS: Intake of dietary antioxidants, such as carotenoids and vitamins, was not associated with the risk of developing PD in Singaporean Chinese. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

15.
Tob Control ; 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546664

RESUMO

BACKGROUND: Little is known about the health harms associated with low-intensity smoking in Asians who, on average, smoke fewer cigarettes and start smoking at a later age than their Western counterparts. METHODS: In this pooled analysis of 738 013 Asians from 16 prospective cohorts, we quantified the associations of low-intensity (<5 cigarettes/day) and late initiation (≥35 years) of smoking with mortality outcomes. HRs and 95% CIs were estimated for each cohort by Cox regression. Cohort-specific HRs were pooled using random-effects meta-analysis. FINDINGS: During a mean follow-up of 11.3 years, 92 068 deaths were ascertained. Compared with never smokers, current smokers who consumed <5 cigarettes/day or started smoking after age 35 years had a 16%-41% increased risk of all-cause, cardiovascular disease (CVD), respiratory disease mortality and a >twofold risk of lung cancer mortality. Furthermore, current smokers who started smoking after age 35 and smoked <5 cigarettes/day had significantly elevated risks of all-cause (HRs (95% CIs)=1.14 (1.05 to 1.23)), CVD (1.27 (1.08 to 1.49)) and respiratory disease (1.54 (1.17 to 2.01)) mortality. Even smokers who smoked <5 cigarettes/day but quit smoking before the age of 45 years had a 16% elevated risk of all-cause mortality; however, the risk declined further with increasing duration of abstinence. CONCLUSIONS: Our study showed that smokers who smoked a small number of cigarettes or started smoking later in life also experienced significantly elevated all-cause and major cause-specific mortality but benefited from cessation. There is no safe way to smoke-not smoking is always the best choice.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32303531

RESUMO

INTRODUCTION: The non-invasive enhanced liver fibrosis (ELF) score-comprising tissue inhibitor of matrix metalloproteinases-1 (TIMP1), hyaluronic acid (HA) and amino-terminal propeptide of type III procollagen (PIIINP)-has been shown to accurately predict fibrosis stages among patients with non-alcoholic fatty liver disease (NAFLD). However, no study has examined whether the ELF score or its components would also be predictive of type 2 diabetes, which commonly coexists and shares the same pathogenic abnormalities with NAFLD. Therefore, we prospectively investigated their associations with type 2 diabetes risks for the first time. RESEARCH DESIGN AND METHODS: The ELF score was measured among 254 type 2 diabetes cases and 254 age-matched and sex-matched controls nested within the prospective Singapore Chinese Health Study. Cases had hemoglobin A1c (HbA1c) levels <6.5% at blood collection (1999-2004) and reported to have diabetes during follow-up II (2006-2010). Controls had HbA1c levels <6.0% at blood-taking and remained free of diabetes at follow-up II. Multivariable conditional logistic regression models were used to assess the ELF-diabetes association. RESULTS: Higher TIMP1 levels were associated with increased type 2 diabetes risk, and the OR comparing the highest versus lowest quartiles was 2.56 (95% CI 1.23 to 5.34; p trend=0.035). However, ELF score, PIIINP and HA were not significantly associated with type 2 diabetes risks. CONCLUSIONS: Higher TIMP1 levels, but not ELF score, PIIIMP and HA, were associated with increased type 2 diabetes risk in Chinese adults. Our results suggested that elevated TIMP1 levels may contribute to the type 2 diabetes development through pathways other than liver fibrosis.

17.
Nutr Cancer ; : 1-7, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32238007

RESUMO

Background: Epidemiological studies have demonstrated separately that patients with kidney stone may have higher dietary intake of zinc and higher risk of developing kidney cancer. We prospectively assessed the associations of dietary zinc and other trace elements with kidney cancer risk for the first time.Methods: We used data from the prospective Singapore Chinese Health Study that recruited 63,257 adult Chinese residing in Singapore between 1993 and 1998. A validated food frequency questionnaire and the Singapore Food Composition Database was used to compute the values of intake for zinc, copper and manganese. We identified incident cancer cases via linkage with nationwide cancer registry, and used Cox proportional hazard models to compute hazard ratio (HR) and 95% confidence interval (CI) for the association with kidney cancer risk.Results: There were 229 incident kidney cancer cases after median follow-up of 20.1 years. Dietary zinc intake was positively associated with higher kidney cancer risk; the HR comparing the extreme quartiles of zinc intake was 1.74 (95% CI: 1.02-2.97; P-trend = 0.033). Conversely, intakes of copper and manganese were not associated with kidney cancer risk.Conclusions: The positive association between dietary zinc and risk of kidney cancer suggests that zinc may be implicated in renal carcinogenesis.

18.
Cancer Epidemiol Biomarkers Prev ; 29(7): 1430-1435, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32284341

RESUMO

BACKGROUND: Intake of tomato and/or lycopene has been associated with reduced risk of several cancers, but there is no report on the association with risk of hepatocellular carcinoma (HCC). METHODS: The associations of tomato and lycopene consumption with risk of HCC were examined in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese ages 45 to 74 years at enrollment. Diet was assessed using a validated semiquantitative food frequency questionnaire. Cox proportional hazard regression models were used to estimate HR and its 95% confidence interval (CI) of HCC with the consumption of tomato and lycopene among all cohort participants, and unconditional logistic regression was used to assess the association by hepatitis B surface antigen (HBsAg) positivity in a nested case-control study. RESULTS: After a mean follow-up of 17.6 years, 561 incident HCC cases were identified. Higher tomato intake was associated with lower risk of HCC after adjustment for potential confounders (P trend < 0.001). Compared with the lowest quartile, HRs (95% CIs) of HCC for the second, third, and fourth quartile of tomato intake were 0.70 (0.56-0.88), 0.73 (0.58-0.92), and 0.63 (0.49-0.81). Among HBsAg-negative individuals, the inverse association remained (P trend = 0.03). There was no association between lycopene intake and HCC risk (P trend = 0.54). CONCLUSIONS: Tomato intake may offer protection against the development of HCC, particularly among individuals without chronic infection with hepatitis B virus. IMPACT: Tomato intake is a low-cost preventative measure against HCC that may help reduce risk due to increasing rates of nonalcoholic fatty liver disease.

19.
Int J Cancer ; 147(7): 1917-1927, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32222976

RESUMO

Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case-control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.e., sum of choline, betaine and methionine), dimethylglycine and trimethylamine N-oxide (TMAO) with pancreatic cancer risk. In the Shanghai cohort, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of choline, betaine, methionine, total methyl donors and TMAO were 0.27 (0.11-0.69), 0.57 (0.31-1.05), 0.50 (0.26-0.96), 0.37 (0.19-0.73) and 2.81 (1.37-5.76), respectively, compared to the lowest quartile. The corresponding figures in the Singapore cohort were 0.85 (0.23-3.17), 0.50 (0.17-1.45), 0.17 (0.04-0.68), 0.33 (0.10-1.16) and 1.42 (0.50-4.04). The inverse associations of methionine and total methyl donors including choline, betaine and methionine with pancreatic cancer risk in both cohorts support that DNA repair and methylation play an important role against the development of pancreatic cancer. In the Shanghai cohort, TMAO, a gut microbiota-derived metabolite of dietary phosphatidylcholine, may contribute to higher risk of pancreatic cancer, suggesting a modifying role of gut microbiota in the dietary choline-pancreatic cancer risk association.

20.
Artigo em Inglês | MEDLINE | ID: mdl-32209585

RESUMO

OBJECTIVE: Hemoglobin A1c (HbA1c) accuracy is important for diabetes diagnosis and estimation of overall glycemia. The G6PD-Asahi variant which causes glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to lower HbA1c independently of glycemia in African ancestry populations. As different G6PD variants occur in Asian ancestry, we sought to identify Asian-specific G6PD variants associated with HbA1c. RESEARCH DESIGN AND METHODS: In eight Asian population-based cohorts, we performed imputation on the X chromosome using the 1000 Genomes reference panel and tested for association with HbA1c (10 005 East Asians and 2051 South Asians). Results were meta-analyzed across studies. We compared the proportion of individuals classified as having diabetes/pre-diabetes by fasting glucose ≥100 mg/dL or HbA1c ≥5.7% units among carriers and non-carriers of HbA1c-associated variants. RESULTS: The strongest association was a missense variant (G6PD-Canton, rs72554665, minor allele frequency=2.2%, effect in men=-0.76% unit, 95% CI -0.88 to -0.64, p=1.25×10-27, n=2844). Conditional analyses identified a secondary distinct signal, missense variant (G6PD-Kaiping, rs72554664, minor allele frequency=1.6%, effect in men=-1.12 % unit, 95% CI -1.32 to -0.92, p=3.12×10-15, pconditional_Canton=7.57×10-11). Adjusting for glucose did not attenuate their effects. The proportion of individuals with fasting glucose ≥100 mg/dL did not differ by carrier status of G6PD-Canton (p=0.21). Whereas the proportion of individuals with HbA1c ≥5.7% units was lower in carriers (5%) compared with non-carriers of G6PD-Canton (30%, p=0.03). CONCLUSIONS: We identified two G6PD variants in East Asian men associated with non-glycemic lowering of HbA1c. Carriers of these variants are more likely to be underdiagnosed for diabetes or pre-diabetes than non-carriers if screened by HbA1c without confirmation by direct glucose measurements.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA