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1.
J Rheumatol ; 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31523044

RESUMO

OBJECTIVE: We aimed to present a systematic evaluation of 47 non Major Histocompatibility Complex (MHC) Ankylosing Spondylitis (AS) susceptibility loci which have been initially discovered through Caucasian Genome-wide association studies (GWASs) in Han Chinese. METHODS: Totally 10,743 samples representing north and south Chinese in four datasets were obtained. After data quality control and imputation, meta-analysis results of 94,621 variants within 47 loci were extracted. Four ERAP1 single-nucleotide polymorphisms (SNPs) and HLA-B27 tag SNP rs13202464 were used for interaction analysis. Population-attributable risk percentages (PARPs) of AS-associated variants were compared. Functional annotation of AS-associated variants were conducted using HaploReg, RegulomeDB and rVarBase Database. RESULTS: We revealed 16 AS-associated variants with nominal evidence in Han Chinese, including rs10865331 (P=6.30×10-10), rs10050860 (P=4.09×10-5) and rs8070463 (P=1.03×10-4). Potential susceptible SNPs within these 47 loci were also identified, such as rs13024541 (2p15), rs17401719 (5q15) and rs62074054 (17q21). Epistatic ineractions between three ERAP1 SNPs (rs17401719, rs30187 and rs10050860) and HLA-B27 were confirmed. Among the 16 AS-associated variants, rs30187 showed weaker risk effect while rs10050860 and rs12504282 seemed to attribute more risk in Han Chinese than Caucasians. Further genomic annotation pinpointed 35 candidate functional SNPs, especially in 2p15, ERAP1 and NPEPPS-TBKBP1 region. CONCLUSION: Our results provided a detailed spectrum of all the reported non-MHC AS susceptibility loci in Han Chinese, which comprehensively exhibited the ethnic heterogeneity of AS susceptibility and highlighted that 2p15, ERAP1 and NPEPPS-TBKBP1 region may play a critical role in AS pathogenesis across diverse populations.

2.
BMJ Open ; 9(7): e022877, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31371282

RESUMO

OBJECTIVE: We tested whether genetic variants near fatty acid desaturases gene (FADS) cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet, interacted with these dietary factors on change in body mass index (BMI). DESIGN: Three FADS variants were examined for gene-diet interactions on long-term (~10 years) changes in BMI and body weight in four prospective cohort studies. SETTING: Population based study. PARTICIPANTS: 11 323 women from the Nurses' Health Study (NHS), 6833 men from the Health Professionals Follow-up Study (HPFS) and replicated in 6254 women from the Women's Health Initiative (WHI) and 5 264 Chinese from the Singapore Chinese Health Study (SCHS). MAIN OUTCOMES: Long-term (~10 years) changes in BMI and body weight. RESULTS: In the NHS and HPFS cohorts, food-sourced n-3 PUFAs intake showed interactions with the FADS rs174570 on changes of BMI (P for interaction=0.02 in NHS, 0.05 in HPFS and 0.007 in combined). Such interactions were replicated in two independent cohorts WHI and SCHS (P for interaction=0.04 in WHI, 0.02 in SCHS and 0.001 in combined). The genetic associations of the FADS rs174570 with changes in BMI increased across the tertiles of n-3 PUFAs in all the cohorts. Fish intake also accentuated the genetic associations of the FADS rs174570 with long-term changes in BMI (pooled P for interaction=0.006). Viewed differently, long chain n-3 PUFAs intake showed stronger association with long-term changes in BMI among the rs174570 T carriers (beta=0.79 kg/m2 per g, p=3×10-5) than the rs174570 non-T carriers (beta=0.16 kg/m2 per g, p=0.08). Similar results were observed for fish intake. CONCLUSIONS: Our hypothesis-driven analyses provide replicable evidence that long chain n-3 PUFAs and fish intakes may interact with the FADS variant on long-term weight gain. Further investigation is needed to confirm our findings in other cohorts.

3.
J Nutr ; 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31386157

RESUMO

BACKGROUND: Combinations of circulating fatty acids may affect the risk of type 2 diabetes (T2D) and coronary artery disease (CAD). No previous studies have identified a dietary pattern predicting fatty acid profiles using reduced rank regression (RRR) and evaluated its associations with the risk of T2D and CAD. OBJECTIVE: The aim of this study was to derive a dietary pattern to explain variation in plasma fatty acid concentrations using RRR and evaluate these in relation to risk of T2D and CAD. METHODS: We derived a dietary pattern using fatty acid concentrations from 711 controls of a nested case-control study in the Singapore Chinese Health Study using RRR with 36 food and beverages as predictors and 19 fatty acid biomarkers as responses. Dietary pattern scores were then calculated for the full cohort of men and women (mean age: 56 y). We followed up 45,411 and 58,065 participants for incident T2D and CAD mortality, respectively. Multivariable Cox regression models were used to estimate HRs and 95% CIs. RESULTS: We identified a dietary pattern high in soy, vegetables, fruits, tea, tomato products, bread, fish, margarine and dairy, and low in rice, red meat, coffee, alcohol, sugar-sweetened beverages, and eggs. This pattern predicted higher circulating n-3 (ω-3) PUFAs (18:3n-3, 20:3n-3, 20:5n-3), odd-chain fatty acids (15:0, 17:0), 18:2n-6 and 20:1, and lower 20:4n-6 and 16:1. During a mean follow-up of 11 y and 19 y, 5207 T2D and 3016 CAD mortality events, respectively, were identified. Higher dietary pattern scores were associated with a lower risk of T2D [multivariable-adjusted HR comparing extreme quintiles, 0.86 (95% CI: 0.79, 0.95); P-trend <0.001] and CAD mortality [HR, 0.76 (95% CI: 0.68, 0.86); P-trend <0.001]. CONCLUSIONS: Dietary patterns reflecting higher circulating n-3 PUFAs, odd-chain fatty acids, and linoleic acid may be associated with lower T2D and CAD risk in Chinese adults. This trial was registered at www.clinicaltrials.gov as NCT03356340.

4.
BMJ Open ; 9(8): e026225, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31444178

RESUMO

OBJECTIVE: To study the association of educational level and risk of death from all causes, cardiovascular disease (CVD) and cancer among Asian populations. DESIGN: A pooled analysis of 15 population-based cohort studies. SETTING AND PARTICIPANTS: 694 434 Asian individuals from 15 prospective cohorts within the Asia Cohort Consortium. INTERVENTIONS: None. MAIN OUTCOME MEASURES: HRs and 95% CIs for all-cause mortality, as well as for CVD-specific mortality and cancer-specific mortality. RESULTS: A total of 694 434 participants (mean age at baseline=53.2 years) were included in the analysis. During a mean follow-up period of 12.5 years, 103 023 deaths were observed, among which 33 939 were due to cancer and 34 645 were due to CVD. Higher educational levels were significantly associated with lower risk of death from all causes compared with a low educational level (≤primary education); HRs and 95% CIs for secondary education, trade/technical education and ≥university education were 0.88 (0.85 to 0.92), 0.81 (0.73 to 0.90) and 0.71 (0.63 to 0.80), respectively (ptrend=0.002). Similarly, HRs (95% CIs) were 0.93 (0.89 to 0.97), 0.86 (0.78 to 0.94) and 0.81 (0.73 to 0.89) for cancer death, and 0.88 (0.83 to 0.93), 0.77 (0.66 to 0.91) and 0.67 (0.58 to 0.77) for CVD death with increasing levels of education (both ptrend <0.01). The pattern of the association among East Asians and South Asians was similar compared with ≤primary education; HR (95% CI) for all-cause mortality associated with ≥university education was 0.72 (0.63 to 0.81) among 539 724 East Asians (Chinese, Japanese and Korean) and 0.61 (0.54 to 0.69) among 154 710 South Asians (Indians and Bangladeshis). CONCLUSION: Higher educational level was associated with substantially lower risk of death among Asian populations.

5.
Am J Clin Nutr ; 110(4): 912-920, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31374567

RESUMO

BACKGROUND: Prospective studies linking dietary pattern and cognitive function in the elderly are limited in Asian populations. OBJECTIVE: We examined the associations between various healthful dietary patterns and risk of cognitive impairment in Chinese adults. METHODS: We used data from the Singapore Chinese Health Study of 16,948 men and women who were aged 45-74 y at baseline (1993-1998) and reinterviewed at the third follow-up visit (2014-2016), ∼20 y later. Diet quality at baseline was assessed 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). Cognitive function was evaluated using a Singapore-modified Mini-Mental State Examination during the third follow-up visit when subjects were aged 61-96 y. Multivariable logistic regression models were used to compute ORs and 95% CIs associated with the risk of cognitive impairment defined using education-specific cut-offs. RESULTS: Cognitive impairment was present in 2443 (14.4%) participants. The OR (95% CI) for cognitive impairment comparing the highest with the lowest quartile of diet quality scores was 0.67 (0.59, 0.77) for aMED, 0.71 (0.62, 0.81) for DASH, 0.75 (0.66, 0.85) for AHEI-2010, 0.82 (0.71, 0.94) for PDI, and 0.78 (0.68, 0.90) for hPDI (all P values for trend <0.001). Each SD increment in different diet quality scores was associated with 7-16% lower risk of cognitive impairment. CONCLUSIONS: These results provide evidence that adherence to healthy dietary patterns in midlife is associated with a lower risk of cognitive impairment in late life in Chinese adults.

6.
PLoS One ; 14(8): e0221697, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31465482

RESUMO

INTRODUCTION: Telomeres and telomerase play important role in maintaining chromosome integrity and genomic stability. Recent epidemiologic data showed inconsistent findings which suggested that both short and long leukocyte telomeres could be associated with increased risk of pancreatic cancer. We prospectively examined the association between telomere length and pancreatic cancer risk in a population-based cohort study. METHODS: The Singapore Chinese Health Study recruited 63,257 Chinese aged 45 to 74 years from 1993 to 1998 in Singapore. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction method in 26,540 participants, including 116 participants who later developed pancreatic cancer after an average of 13 years of follow-up. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and its 95% confidence interval (CI) of pancreatic cancer risk associated with telomere length, with adjustment for confounding factors. RESULTS: Longer telomeres were significantly associated with higher risk of pancreatic cancer (Ptrend = 0.02). Compared with lowest quartile, subjects with highest quartile of telomere length had an HR of 2.18 (95% CI: 1.25-3.80) for developing pancreatic cancer. In stratified analysis, this association remained among pancreatic adenocarcinoma patients but not among pancreatic non-adenocarcinoma patients. In continuous scale, the HRs and 95% CIs were 3.08 (1.17-8.11) for adenocarcinoma patients and 1.47 (0.43-5.06) for non-adenocarcinoma patients. The HRs and 95% CIs of the highest quartile of telomere length, compared with the lowest quartile, for adenocarcinoma and non-adenocarcinoma were 2.50 (1.22-5.13) and 1.63 (0.66-4.03), respectively. The length of follow-up from the collection of blood for the measurement of telomere length to the diagnosis of cancer (median = 8.0, range: from 5.0 months to 16.2 years) had no significant impact on the association between telomere length and pancreatic cancer risk. CONCLUSIONS: The present study demonstrates that longer telomeres are associated with increased risk of overall pancreatic cancer.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31399476

RESUMO

BACKGROUND: To date, few epidemiologic studies have been conducted to elucidate lifestyle-related risk factors for multiple myeloma in Asia. We investigated the association of body mass index (BMI), smoking, and alcohol intake with the risk of multiple myeloma mortality through a pooled analysis of more than 800,000 participants in the Asia Cohort Consortium. METHODS: The analysis included 805,309 participants contributing 10,221,623 person-years of accumulated follow-up across Asia Cohort Consortium cohorts. HRs and 95% confidence intervals (95% CI) for the association between BMI, smoking, and alcohol at baseline and the risk of multiple myeloma mortality were assessed using a Cox proportional hazards model with shared frailty. RESULTS: We observed a statistically significant dose-dependent association between BMI categories and the risk of multiple myeloma mortality (<18.5 kg/m2: HR = 0.80, 95% CI: 0.52-1.24; 18.5-24.9 kg/m2: reference; 25.0-29.9 kg/m2: HR = 1.17, 95% CI: 0.94-1.47; ≥30 kg/m2: HR = 1.61, 95% CI: 0.99-2.64, P trend = 0.014). By sex, this association was more apparent in women than in men (P for heterogeneity between sexes = 0.150). We observed no significant associations between smoking or alcohol consumption and risk of multiple myeloma mortality. CONCLUSIONS: This study showed that excess body mass is associated with an increased risk of multiple myeloma mortality among Asian populations. In contrast, our results do not support an association between smoking or alcohol consumption and the risk of multiple myeloma mortality in Asian populations. IMPACT: This study provides important evidence on the association of BMI, smoking, and alcohol with the risk of multiple myeloma mortality in Asian populations.

9.
Eur J Nutr ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227861

RESUMO

PURPOSE: Epidemiological studies directly investigating the association between different types of meat intake and cognitive impairment are limited. We, therefore, examined this association in the Singapore Chinese Health Study. METHODS: In total, 16,948 participants were included in analysis. Diet was measured by a 165-item semiquantitative food-frequency questionnaire at baseline (1993-1998) when participants were 45-74 years. Cognitive impairment was defined using a Singapore modified version of Mini-Mental State Examination during follow-up three visits (2014-2016) when participants were 61-96 years. Multivariable logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI). RESULTS: Cognitive impairment was present in 2443 (14.4%) participants. Compared to the lowest quartile, the highest quartile of red meat intake was associated with increased risk of cognitive impairment (OR 1.16, 95% CI 1.01-1.32, P for trend = 0.009), while the corresponding value for poultry intake was 0.89 (95% CI 0.78-1.02, P for trend = 0.10). Higher fresh fish/shellfish was associated with a lower risk of cognitive impairment (OR 0.88, 95% CI 0.77-1.00, P for trend = 0.03), while preserved fish/shellfish intake was associated with a higher risk (OR 1.19, 95% CI 1.04-1.36, P for trend = 0.01). CONCLUSION: This study found that a higher intake of red meat in midlife was associated with increased likelihood of cognitive impairment in later life, while substitution of red meat intake with poultry or fresh fish/shellfish was associated with reduced risk.

10.
Nat Commun ; 10(1): 2491, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171785

RESUMO

Genetic factors underlying leukocyte telomere length (LTL) may provide insights into telomere homeostasis, with direct links to disease susceptibility. Genetic evaluation of 23,096 Singaporean Chinese samples identifies 10 genome-wide loci (P < 5 × 10-8). Several of these contain candidate genes (TINF2, PARP1, TERF1, ATM and POT1) with potential roles in telomere biology and DNA repair mechanisms. Meta-analyses with additional 37,505 European individuals reveals six more genome-wide loci, including associations at MPHOSPH6, NKX2-3 and TYMS. We demonstrate that longer LTL associates with protection against respiratory disease mortality [HR = 0.854(0.804-0.906), P = 1.88 × 10-7] in the Singaporean Chinese samples. We further show that the LTL reducing SNP rs7253490 associates with respiratory infections (P = 7.44 × 10-4) although this effect may not be strongly mediated through LTL. Our data expands on the genetic basis of LTL and may indicate on a potential role of LTL in immune competence.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Reparo do DNA/genética , Leucócitos/metabolismo , Homeostase do Telômero/genética , Telômero/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/genética , Singapura , Adulto Jovem
11.
Eur J Nutr ; 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161350

RESUMO

PURPOSE: It is unclear if midlife consumption of dairy and soy food intake, and their components of calcium and isoflavones (in soy), is related to cognitive impairment in elderly. METHODS: We used baseline data on lifestyle and habitual diet of 16,948 participants collected during their recruitment into the Singapore Chinese Health Study from 1993 to 1998, and data on their cognitive function, measured using a 30-item Singapore modified Mini-Mental State Examination, during follow-up interviews from 2014 to 2016. We used multivariable logistic regression models to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for developing cognitive impairment. RESULTS: Higher dairy intake was associated with a lower risk of cognitive impairment in a dose-dependent manner (P for trend = 0.009). Compared to the lowest quartile of dairy intake, ORs (95% CIs) were 0.93 (0.81-1.07) for the second, 0.88 (0.76-1.01) for the third, and 0.82 (0.72-0.94) for the fourth quartiles of intake. Similar results were found for dairy calcium intake (P for trend = 0.008). However, there was no statistically significant association for intake of soy (OR comparing extreme quartiles 0.99, 95% CI 0.87-1.14, P for trend = 0.92), isoflavones (OR 1.01, 95% CI 0.88-1.15, P for trend = 0.90) or non-dairy calcium (OR 1.06, 95% CI 0.86-1.30, P for trend = 0.81) with risk of cognitive impairment. CONCLUSIONS: Dairy intake at midlife could have a protective association against cognitive impairment that may not be attributed to its calcium content alone, while soy or isoflavone intake was not associated with the cognition of elderly in our study.

12.
Cancer Causes Control ; 30(8): 847-857, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154549

RESUMO

PURPOSE: Soy isoflavones and tea catechins have immunomodulating and chemopreventive properties relevant for cervical carcinogenesis; however, there are limited epidemiologic data on the relationship of soy and tea consumption with cervical cancer risk. The aim of our study was to examine effects of soy and tea intake on cervical cancer risk among Singapore Chinese women. METHODS: The association between intake of soy and tea drinking and cervical cancer risk was investigated in a prospective, population-based cohort of 30,744 Chinese women in Singapore with an average 16.7 years of follow-up and 312 incident cervical cancer cases. Multivariable proportional hazard models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of cervical cancer associated with intake levels of soy and tea. RESULTS: High intake of soy alone was associated with a statistically borderline significant 20% reduced risk of cervical cancer (HR 0.80, 95% CI 0.61, 1.05) while green tea alone was not (HR 0.97, 95% CI: 0.76, 1.22). In stratified analysis, high intake of soy was associated with a statistically significant decrease in cervical cancer risk among green tea drinkers (HR 0.43; 95% CI 0.28, 0.69) but not among non-drinkers of green tea. The difference in the soy-cervical cancer risk association between green tea drinkers and non-drinkers was statistically significant (p for interaction = 0.004). This inverse association between soy intake and cervical cancer risk remained after further adjustment for human papillomavirus serostatus. Black tea consumption was not associated with cervical cancer risk. CONCLUSIONS: These findings suggest that a protective effect of soy against cervical cancer development may depend on green tea constituents.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31094422

RESUMO

BACKGROUND: Dietary intakes of B vitamins (e.g., folate) are related to cognitive function according to epidemiologic studies in western countries. But prospective studies in Asian populations are scarce. This study evaluated the relations of dietary intakes of six B vitamins in midlife with cognitive impairment in old age in a Chinese population living in Singapore. METHODS: This study included 16,948 participants from the Singapore Chinese Health Study, a population-based prospective cohort. Baseline dietary intakes of B vitamins were assessed using a validated 165-item food frequency questionnaire when the participants were 45-74 years (1993-1998). After an average follow-up of 20 years, cognitive function was examined using a Singapore-modified version of Mini-Mental State Examination (SM-MMSE) scale in 2014-2016, and cognitive impairment was defined using education-specific cut-offs. Logistic regression models were applied to estimate the association between B vitamins and cognitive impairment. All the six B vitamins were mutually adjusted in the final model. RESULTS: In the 2014-2016 interview, 2,443 participants were defined as cognitive impairment. Riboflavin and folate were significantly and independently associated with cognitive impairment in a dose-dependent manner: the odds ratio (95% confidence interval) comparing the highest with the lowest quartile was 0.82 (0.69, 0.97) for riboflavin, and 0.83 (0.70, 0.98) for folate (both p-trend <.05). Dietary intakes of thiamine, niacin, vitamin B-6 and B-12 were not significantly associated with risk of cognitive impairment. CONCLUSIONS: Higher dietary intakes of riboflavin and folate in midlife were associated with a lower risk of cognitive impairment in late-life in the Chinese population.

14.
Clin Transl Gastroenterol ; 10(5): 1-9, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117113

RESUMO

OBJECTIVES: Telomeres and telomerase play important roles in maintaining chromosome integrity and genomic stability. To address a lack of consensus about the association between leukocyte telomere length and colorectal cancer, we investigated this association in the Singapore Chinese Health Study. METHODS: Relative telomere length in white blood cells was quantified using a validated quantitative polymerase chain reaction method in 26,761 participants, including 776 incident colorectal cancer cases. The Cox proportional hazard regression method was used to calculate the hazard ratio and the corresponding 95% confidence interval (CI) for colorectal cancer associated with longer telomeres. RESULTS: Longer telomeres were significantly associated with a higher risk of colorectal cancer (Ptrend = 0.02). Compared with the lowest quartile, subjects with the highest quartile of telomere length had a hazard ratio of 1.32 (95% CI: 1.08-1.62) for developing colorectal cancer. The corresponding elevation in rectal cancer risk for the highest quartile of telomere length was 71% (95% CI: 22-140, Ptrend = 0.02). There was no statistically significant association between telomere length and risk of colon cancer. DISCUSSION: This large cohort study of Singapore Chinese, the first study using a cohort study design with more than 26,000 participants that yielded 776 incidence colorectal cancer cases during 12 years of follow-up, provides evidence in support of longer telomeres being associated with a higher risk of colorectal cancer, particularly rectal cancer.

15.
Am J Epidemiol ; 188(8): 1503-1511, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31107539

RESUMO

Infants and children are particularly vulnerable to in utero and early-life exposures. Thus, a mother's exposures before and during pregnancy could have important consequences for her child's health, including cancer development. We examined whether birth certificate-derived maternal anthropometric characteristics were associated with increased risk of subsequent childhood cancer development, accounting for established maternal and infant risk factors. Pennsylvania birth and cancer registry files were linked by the state Department of Health, yielding a virtual cohort of births and childhood cancers from 2003 through 2016. The analysis included 1,827,875 infants (13,785,309 person-years at risk), with 2,352 children diagnosed with any cancer and 747 with leukemia before age 14 years. Children born to mothers with a body mass index (weight (kg)/height (m)2) of ≥40 had a 57% (95% confidence interval: 12, 120) higher leukemia risk. Newborn size of ≥30% higher than expected was associated with 2.2-fold and 1.8-fold hazard ratios for total childhood cancer and leukemia, respectively, relative to those with expected size. Being <30% below expected size also increased the overall cancer risk (P for curvilinearity < 0.0001). Newborn size did not mediate the association between maternal obesity and childhood cancer. The results suggest a significant role of early-life exposure to maternal obesity- and fetal growth-related factors in childhood cancer development.

16.
JAMA Netw Open ; 2(4): e192696, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31002328

RESUMO

Importance: Asia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations. Objectives: To evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants' age, sex, education level, body mass index, and smoking status. Design, Setting, and Participants: This pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018. Exposures: Doctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (P for interaction < .001) and more evident among adults aged 30 to 49 years (HR, 2.43; 95% CI, 2.08-2.84) than among adults aged 70 years and older (HR, 1.51; 95% CI, 1.40-1.62) (P for interaction < .001). A similar pattern of association was found between diabetes and cause-specific mortality, with significant variations noted by sex and age. Conclusions and Relevance: This study found that diabetes was associated with increased risk of death from several diseases among Asian populations. Development and implementation of diabetes management programs are urgently needed to reduce the burden of diabetes in Asia.

17.
Int J Cancer ; 2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31001807

RESUMO

Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and ß-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher ß-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; ptrend = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; ptrend = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between ß-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association.

18.
Breast Cancer Res ; 21(1): 50, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30995937

RESUMO

BACKGROUND: Telomeres and telomerase play key roles in the chromosomal maintenance and stability. Recent epidemiological studies have shown that longer telomeres are associated with increased risk of several cancer types. However, epidemiological data for telomere length and risk of breast cancer are sparse. METHODS: We prospectively studied the association between telomere length and risk of breast cancer in 14,305 middle-aged or older Chinese women of the Singapore Chinese Health Study including 442 incident breast cancer cases after 12.3 years of follow-up. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiple quantitative polymerase chain reaction method. The Cox proportional hazard regression method was used to estimate hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for breast cancer associated with longer telomeres after adjustment for potential confounders. RESULTS: Longer telomeres were significantly associated with higher risk of breast cancer in a dose-dependent manner (Ptrend = 0.006); the highest quartile of telomere length was associated with a statistically significant 47% higher risk of breast cancer compared with the lowest quartile of telomere length after the adjustment for age and other known risk factors for breast cancer (HRQ4 vs Q1 = 1.47, 95% CI = 1.11, 1.94). CONCLUSIONS: The findings of the present study support the hypothesis that longer telomeres may be a risk factor for breast cancer. Telomere length in peripheral blood leukocytes may be developed as a biomarker for breast cancer risk prediction.

19.
Diabetes Metab J ; 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30968617

RESUMO

BACKGROUND: Fetuin-A is a hepatokine that involved in the pathogenesis of insulin resistance. Previous epidemiological studies have found a positive association between blood fetuin-A and type 2 diabetes mellitus (T2DM) risk among Caucasians and African Americans. We aimed to investigate the prospective relationship between fetuin-A and T2DM in an Asian population for the first time. METHODS: A nested case-control study was established within a prospective cohort of Chinese living in Singapore. At blood collection (1999 to 2004), all participants were free of diagnosed T2DM and aged 50 to 79 years. At subsequent follow-up (2006 to 2010), 558 people reported to have T2DM and were classified as incident cases, and 558 controls were randomly chosen from the participants who did not develop T2DM to match with cases on age, sex, dialect group, and date of blood collection. Plasma fetuin-A levels were measured retrospectively in cases and controls using samples collected at baseline. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI). Restricted cubic spline analysis was used to examine a potential non-linear association between fetuin-A levels and T2DM risk. RESULTS: Compared with those in the lowest fetuin-A quintile, participants in the highest quintile had a two-fold increased risk of developing T2DM (OR, 2.06; 95% CI, 1.21 to 3.51). A non-linear association was observed (P nonlinearity=0.005), where the association between fetuin-A levels and T2DM risk plateaued at plasma concentrations around 830 µg/mL. CONCLUSION: There is a positive association between plasma fetuin-A levels and risk of developing T2DM in this Chinese population.

20.
JAMA Netw Open ; 2(3): e191474, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30924901

RESUMO

Importance: Understanding birth cohort-specific tobacco smoking patterns and their association with total and cause-specific mortality is important for projecting future deaths due to tobacco smoking across Asian populations. Objectives: To assess secular trends of tobacco smoking by countries or regions and birth cohorts and evaluate the consequent mortality in Asian populations. Design, Setting, and Participants: This pooled meta-analysis was based on individual participant data from 20 prospective cohort studies participating in the Asia Cohort Consortium. Between September 1, 2017, and March 31, 2018, a total of 1 002 258 Asian individuals 35 years or older were analyzed using Cox proportional hazards regression analysis and random-effects meta-analysis. The pooled results were presented for mainland China; Japan; Korea, Singapore, and Taiwan; and India. Exposures: Tobacco use status, age at starting smoking, number of cigarettes smoked per day, and age at quitting smoking. Main Outcomes and Measures: Country or region and birth cohort-specific mortality and the population attributable risk for deaths from all causes and from lung cancer. Results: Of 1 002 258 participants (51.1% women and 48.9% men; mean [SD] age at baseline, 54.6 [10.4] years), 144 366 deaths (9158 deaths from lung cancer) were ascertained during a mean (SD) follow-up of 11.7 (5.3) years. Smoking prevalence for men steadily increased in China and India, whereas it plateaued in Japan and Korea, Singapore, and Taiwan. Among Asian male smokers, the mean age at starting smoking decreased in successive birth cohorts, while the mean number of cigarettes smoked per day increased. These changes were associated with an increasing relative risk of death in association with current smoking in successive birth cohorts of pre-1920, 1920s, and 1930 or later, with hazard ratios for all-cause mortality of 1.26 (95% CI, 1.17-1.37) for the pre-1920 birth cohort, 1.47 (95% CI, 1.35-1.61) for the 1920s birth cohort, and 1.70 (95% CI, 1.57-1.84) for the cohort born in 1930 or later. The hazard ratios for lung cancer mortality were 3.38 (95% CI, 2.25-5.07) for the pre-1920 birth cohort, 4.74 (95% CI, 3.56-6.32) for the 1920s birth cohort, and 4.80 (95% CI, 3.71-6.19) for the cohort born in 1930 or later. Tobacco smoking accounted for 12.5% (95% CI, 8.4%-16.3%) of all-cause mortality in the pre-1920 birth cohort, 21.1% (95% CI, 17.3%-24.9%) of all-cause mortality in the 1920s birth cohort, and 29.3% (95% CI, 26.0%-32.3%) of all-cause mortality for the cohort born in 1930 or later. Tobacco smoking among men accounted for 56.6% (95% CI, 44.7%-66.3%) of lung cancer mortality in the pre-1920 birth cohort, 66.6% (95% CI, 58.3%-73.5%) of lung cancer mortality in the 1920s birth cohort, and 68.4% (95% CI, 61.3%-74.4%) of lung cancer mortality for the cohort born in 1930 or later. For women, tobacco smoking patterns and lung cancer mortality varied substantially by countries and regions. Conclusions and Relevance: In this study, mortality associated with tobacco smoking continued to increase among Asian men in recent birth cohorts, indicating that tobacco smoking will remain a major public health problem in most Asian countries in the coming decades. Implementing comprehensive tobacco-control programs is warranted to end the tobacco epidemic.

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