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1.
JAMA Netw Open ; 2(9): e1911970, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31539079

RESUMO

Importance: Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood. Objective: To assess the association between metabolomics and lung cancer risk among never-smoking women. Design, Setting, and Participants: This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018. Exposures: Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured. Main Outcomes and Measures: Incident lung cancer. Results: Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odds ratio for second tertile, 0.52 [95% CI, 0.34-0.80]; and odds ratio for third tertile, 0.46 [95% CI, 0.30-0.70]), and the association was consistent across different histological subtypes and follow-up times. Additionally, metabolic pathway analysis found several systemic biological alterations that were associated with lung cancer risk, including 1-carbon metabolism, nucleotide metabolism, oxidative stress, and inflammation. Conclusions and Relevance: This prospective study of the untargeted urinary metabolome and lung cancer among never-smoking women in China provides support for the hypothesis that soy-based metabolites are associated with lower lung cancer risk in never-smoking women and suggests that biological processes linked to air pollution may be associated with higher lung cancer risk in this population.

2.
Int J Epidemiol ; 2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31377785

RESUMO

BACKGROUND: Lifetime use of bituminous ('smoky') coal is associated with nearly a 100-fold higher risk of lung cancer mortality compared with anthracite ('smokeless') coal use in rural Xuanwei, China, among women. Risk of mortality from ischaemic heart disease (IHD) and stroke for these coal types has not been evaluated. METHODS: A cohort of 16 323 non-smoking women in Xuanwei, who were lifetime users of either smoky or smokeless coal, were followed up from 1976 to 2011. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) to evaluate lifetime use of coal types and stoves in the home in relation to risk of IHD and stroke mortality. RESULTS: Among lifetime users of smokeless coal, higher average exposure intensity (≥4 tons/year vs <2.5 tons/year, HR = 7.9, 95% CI = 3.5-17.8; Ptrend =<0.0001) and cumulative exposure (>64 ton-years vs ≤28 ton-years, HR = 6.5, 95% CI = 1.5-28.3; Ptrend =0.003) during follow-up and over their lifetime was associated with increased IHD mortality, and ventilated stove use dramatically reduced this risk (HR = 0.2, 95% CI 0.1-0.5). Higher cumulative exposure to smoky coal during follow-up showed positive associations with IHD mortality, but the evidence for other metrics was less consistent compared with associations with smokeless coal use. CONCLUSIONS: Higher use of smokeless coal, which is burned throughout China and is generally regarded to be a cleaner fuel type, is associated with IHD mortality. Use of cleaner fuels or stove interventions may be effective in reducing the increasing burden of IHD in developing regions that currently rely on smokeless coal for cooking and heating.

3.
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.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31387969

RESUMO

BACKGROUND: Regular aspirin use may lower ovarian cancer risk by blocking the cyclooxygenase enzymes, resulting in lower expression of prostaglandins, including prostaglandin E2 (PGE2). We evaluated whether higher prediagnosis PGE-M (a urinary biomarker of PGE2) was associated with increased ovarian cancer risk in three prospective cohorts. METHODS: We conducted a case-control study nested in the Nurses' Health Study (NHS), NHSII, and Shanghai Women's Health Study. Our analyses included 304 cases of epithelial ovarian cancer diagnosed from 1996 to 2015 and 600 matched controls. We measured urinary PGE-M using LC/MS with normalization to creatinine. Measures from each study were recalibrated to a common standard. We estimated ORs and 95% confidence intervals (CI) using conditional logistic regression, with PGE-M levels modeled in quartiles. Multivariable models were adjusted for ovarian cancer risk factors. RESULTS: There was no evidence of an association between urinary PGE-M levels and ovarian cancer risk for women with PGE-M levels in the top versus bottom quartile (OR = 0.80; 95% CI, 0.51-1.27; P trend = 0.37). We did not observe heterogeneity by histotype (P = 0.53), and there was no evidence of effect modification by body mass index (P interaction = 0.82), aspirin use (P interaction = 0.59), or smoking (P interaction = 0.14). CONCLUSIONS: Prediagnosis urinary PGE-M levels were not significantly associated with ovarian cancer risk. Larger sample sizes are needed to consider a more modest association and to evaluate associations for specific tumor subtypes. IMPACT: Systemic prostaglandin levels do not appear strongly associated with ovarian cancer risk. Future research into aspirin use and ovarian cancer risk should consider local prostaglandins and prostaglandin-independent mechanisms.

5.
J Urol ; : 101097JU0000000000000493, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31430246

RESUMO

PURPOSE: High animal protein intake is a risk factor for nephrolithiasis. Whether plant based sources of protein are associated with kidney stone risk is not well studied. We examined the association of animal and plant protein intake with the risk of incident kidney stones in Shanghai, China. MATERIALS AND METHODS: Dietary intakes were obtained from a validated food frequency questionnaire at baseline. Self-reported stone events were ascertained at baseline and at followup visits. Multivariable Cox regression models were used to evaluate the associations of protein intake with the incident stone risk. RESULTS: During 319,211 and 696,950 person-years of followup 1,451 men and 1,202 women, respectively, reported incident stones. The average ± SD intake of animal and plant protein standardized to 2,000 Kcal was 31.3 ± 13.7 and 48.4 ± 7.2 gm per day in women, and 30.8 ± 13.3 and 51.3 ± 7.6 gm per day, respectively, in men. On multivariable analysis participants in the highest quintiles of animal and nondairy animal protein intake showed an increased risk of incident stones compared to those in the lowest quintiles (HR 1.16, 95% CI 1.01-1.32, p=0.03, vs HR 1.14, 95% CI 1.01-1.30, p=0.04). Compared to the lowest quintile the highest intake quintiles of the animal-to-plant protein ratios and the nondairy animal-to-plant protein ratios were positively associated with stone risk (HR 1.17, 95% CI 1.03-1.33, p=0.02, and HR 1.20, 95% CI 1.06-1.36, p=0.005, respectively). No association was observed with plant protein intake (ptrend=0.14). CONCLUSIONS: In this population with a relatively low animal protein intake and a high plant protein intake, a greater animal protein intake was associated with a kidney stone risk. Increasing the proportion of plant protein relative to animal protein appeared protective against the risk.

6.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1712-1719, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31387968

RESUMO

BACKGROUND: No epidemiologic studies have directly assessed the association between dietary and urinary isoflavonoids and risk of liver cancer in humans. METHODS: A nested case-control study, including 217 incident cases of liver cancer and 427 individually matched control subjects, was conducted in Shanghai, China. Dietary isoflavonoid intakes were assessed through a validated food-frequency questionnaire and the Chinese Food Composition Tables. Urinary excretion levels of four major isoflavonoids were measured by the reversed-phase high-performance liquid chromatography. ORs and 95% confidence intervals (CI) were derived using conditional logistic regression models. RESULTS: The adjusted ORs (95% CIs) for liver cancer across increasing quartiles of urinary genistein levels were 1.00 (reference), 0.55 (95% CI, 0.22-1.36), 0.57 (95% CI, 0.23-1.43), and 0.19 (95% CI, 0.06-0.59) (P trend = 0.008) in women and 1.00 (reference), 1.22 (0.52-2.86), 1.17(0.47-2.90), and 1.23 (0.55-2.76) in men, respectively. These associations were consistent by limiting the cases to primary malignant neoplasm of liver or malignant neoplasms of the intrahepatic bile ducts, or among participants without self-reported liver disease or cirrhosis at the baseline survey. No associations were found between dietary isoflavonoids and liver cancer risk. CONCLUSIONS: Our study suggests for the first time that urinary excretion of genistein may be associated with reduced risk of liver cancer in women. IMPACT: In this nested case-control study in China, we found that urinary excretion of genistein was associated with lower risk of liver cancer in women, and not in men.

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.

8.
Eur J Prev Cardiol ; : 2047487319862066, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288541

RESUMO

BACKGROUND: The recent American College of Cardiology/American Heart Association guidelines for high blood pressure lowered the hypertension criteria from systolic/diastolic blood pressure (SBP/DBP) of 140/90 mmHg or greater to 130/80 mmHg or greater, while the potential impact of the change on Chinese adults remains unclear. DESIGN: A pooled prospective cohort analysis. METHODS: Included were 154,407 Chinese adults from three prospective cohorts, which measured blood pressure at baseline and follow-up visits, and tracked death events by linkages to medical insurance system or vital statistics registries. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a total follow-up of 1,718,089 person-years, 14,692 deaths were documented including 5086 cardiovascular deaths (1277 ischaemic heart disease and 2509 cerebrovascular disease deaths). Compared to normal blood pressure (SBP/DBP < 120/80 mmHg), newly defined stage 1 hypertension (SBP/DBP 130-139/80-89 mmHg) was associated with increased cardiovascular mortality (HR 1.40, 95% CI 1.16-1.69; HR 1.36, 95% CI 1.12-1.65 for ischaemic heart disease mortality; HR 1.53, 95% CI 1.18-2.00 for cerebrovascular mortality), but not with all-cause mortality (HR 1.04, 95% CI 0.89-1.21). Stage 2 hypertension (SBP/DBP ≥ 140/90 mmHg) showed significant associations with cardiovascular disease and all-cause mortality, while elevated blood pressure (SBP 120-129 mmHg and DBP < 80 mmHg) showed null associations. The associations were stronger in adults younger than 65 years and adults without pre-existing cardiovascular disease compared with their counterparts (P for heterogeneity < 0.05). CONCLUSIONS: The newly defined stage 1 hypertension is associated with an increased risk of cardiovascular disease mortality in the Chinese population, particularly among younger adults and those without a history of cardiovascular disease.

9.
Int J Cancer ; 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31276202

RESUMO

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

10.
Int J Cancer ; 2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351006

RESUMO

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case-cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case-control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR Q1:Q4 ) for GNCA in NIT was 1.35 (95% CI: 0.89-2.05; p-trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02-2.70; p-trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR Q1:Q4 = 2.00, 95% CI: 1.45-2.77; p-trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR Q1:Q4 = 0.65, 95% CI: 0.45-0.92; p-trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence.

11.
Int J Epidemiol ; 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31203367

RESUMO

BACKGROUND: Understanding the association between diet and colorectal cancer (CRC) risk is essential to curbing the epidemic of this cancer. This study prospectively evaluated adherence to the Chinese Food Pagoda (CHFP), and two American Dietary Guidelines: the Alternative Healthy Eating Index (AHEI-2010) and the Dietary Approaches to Stop Hypertension (DASH) in association with CRC risk among Chinese adults living in urban Shanghai, China. METHODS: Participants included 60 161 men and 72 445 women aged 40-74, from two ongoing population-based prospective cohort studies. Associations between dietary guideline compliance scores and CRC risk were evaluated by Cox proportional hazard regression analyses, with age as time metric, and potential confounders were adjusted. RESULTS: We identified 1670 CRC incidence cases (691 males and 979 females) during an average 8.1 years of follow-up for men and 13.4 years for women. CHFP score was inversely associated with risk of CRC, with hazard ratios (HRs) (95% confidence intervals) of 0.88 (0.77, 1.00), 0.86 (0.75, 0.98) and 0.84 (0.73, 0.96) for the 2nd, 3rd and 4th quartiles versus 1st quartile, respectively (Ptrend= 0.01). The inverse association appeared stronger for rectal cancer, individuals at younger age (< 50 years), with a lower BMI (<25 kg/m2) or without any metabolic conditions at baseline, although no multiplicative interactions were noted. No consistent association pattern was observed for the modified DASH score and the modified AHEI-2010. CONCLUSIONS: Compliance with the Dietary Guidelines for Chinese was associated with reduced risk of CRC among Chinese adults. To maximize health impacts, dietary recommendations need to be tailored for specific populations.

12.
Am J Epidemiol ; 188(8): 1512-1528, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31062847

RESUMO

Using time-dependent Cox regression models, we examined associations of common antihypertensive medications with overall cancer survival (OS) and disease-specific survival (DSS), with comprehensive adjustment for potential confounding factors. Participants were from the Shanghai Women's Health Study (1996-2000) and Shanghai Men's Health Study (2002-2006) in Shanghai, China. Included were 2,891 incident breast, colorectal, lung, and stomach cancer cases. Medication use was extracted from electronic medical records. With a median 3.4-year follow-up after diagnosis (interquartile range, 1.0-6.3), we found better outcomes among users of angiotensin II receptor blockers with colorectal cancer (OS: adjusted hazard ratio (HR) = 0.62, 95% confidence interval (CI): 0.44, 0.86; DSS: adjusted HR = 0.61, 95% CI: 0.43, 0.87) and stomach cancer (OS: adjusted HR = 0.62, 95% CI: 0.41, 0.94; DSS: adjusted HR = 0.63, 95% CI: 0.41, 0.98) and among users of ß-adrenergic receptor blockers with colorectal cancer (OS: adjusted HR = 0.50, 95% CI: 0.35, 0.72; DSS: adjusted HR = 0.50, 95% CI: 0.34, 0.73). Better survival was also found for calcium channel blockers (DSS: adjusted HR = 0.67, 95% CI: 0.47, 0.97) and diuretics (OS: adjusted HR = 0.66, 95% CI: 0.45, 0.96; DSS: adjusted HR = 0.57, 95% CI: 0.38, 0.85) with stomach cancer. Our findings suggest angiotensin II receptor blockers, ß-adrenergic receptor blockers, and calcium channel blockers might be associated with improved survival outcomes of gastrointestinal cancers.

13.
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.

14.
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.

15.
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.

16.
BMJ ; 364: k4981, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606716

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. DESIGN: Nested case-control study. SETTING: 20 population based cohort studies in Asia, Europe, Australia, and the United States. PARTICIPANTS: 5299 patients with incident lung cancer, with individually incidence density matched controls. EXPOSURE: Circulating hsCRP concentrations in prediagnostic serum or plasma samples. MAIN OUTCOME MEASURE: Incident lung cancer diagnosis. RESULTS: A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. CONCLUSIONS: Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.


Assuntos
Proteína C-Reativa/metabolismo , Carcinoma de Células Grandes/sangue , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Pulmonares/sangue , Fumar/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Ex-Fumantes/estatística & dados numéricos , Feminino , Humanos , Neoplasias Pulmonares/epidemiologia , Masculino , Pessoa de Meia-Idade , não Fumantes/estatística & dados numéricos , Razão de Chances , Estudos Prospectivos , Medição de Risco , Sensibilidade e Especificidade , Fumantes/estatística & dados numéricos , Fumar/epidemiologia , Adulto Jovem
17.
J Am Heart Assoc ; 8(1): e010606, 2019 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-30606084

RESUMO

Background Trimethylamine-N-oxide ( TMAO ), a diet-derived, gut microbial-host cometabolite, has been associated with adverse cardiovascular outcomes in patient populations; however, evidence is lacking from prospective studies conducted in general populations and non-Western populations. Methods and Results We evaluated urinary levels of TMAO and its precursor metabolites (ie, choline, betaine, and carnitine) in relation to risk of coronary heart disease ( CHD ) among Chinese adults in a nested case-control study, including 275 participants with incident CHD and 275 individually matched controls. We found that urinary TMAO , but not its precursors, was associated with risk of CHD . The odds ratio for the highest versus lowest quartiles of TMAO was 1.91 (95% CI, 1.08-3.35; Ptrend=0.008) after adjusting for CHD risk factors including obesity, diet, lifestyle, and metabolic diseases and 1.75 (95% CI, 0.96-3.18; Ptrend=0.03) after further adjusting for potential confounders or mediators including central obesity, dyslipidemia, inflammation, and intake of seafood and deep-fried meat or fish, which were associated with TMAO level in this study. The odds ratio per standard deviation increase in log- TMAO was 1.30 (95% CI, 1.03-1.63) in the fully adjusted model. A history of diabetes mellitus modified the TMAO - CHD association. A high TMAO level (greater than or equal to versus lower than the median) was associated with odds ratios of 6.21 (95% CI, 1.64-23.6) and 1.56 (95% CI, 1.00-2.43), respectively, among diabetic and nondiabetic participants ( Pinteraction=0.02). Diabetes mellitus status also modified the associations of choline, betaine, and carnitine with risk of CHD ; significant positive associations were found among diabetic participants, but null associations were noted among total and nondiabetic participants. Conclusions Our study suggests that TMAO may accelerate the development of CHD , highlighting the importance of diet-gut microbiota-host interplay in cardiometabolic health.

18.
J Diabetes ; 11(1): 55-64, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29893042

RESUMO

BACKGROUND: Low birth weight (LBW) has been associated with subsequent risks of obesity and certain chronic diseases, but evidence for the associations is limited for the Chinese population. METHODS: In this study we analyzed data from two population-based prospective cohort studies, the Shanghai Women's Health Study and the Shanghai Men's Health Study, to examine the associations between LBW and the risk of obesity and chronic diseases. Birth weight was self-reported at baseline; anthropometric measurements were made at study enrollment. Type 2 diabetes mellitus (T2DM) diagnoses were self-reported, whereas hypertension diagnoses were based on self-report and blood pressure measurements at baseline and follow-up surveys. RESULTS: Birth weight was available for 11 515 men and 13 569 women. Non-linear associations were observed for birth weight with baseline body mass index (BMI), waist circumference (WC), waist: hip ratio (WHR), and waist: height ratio (WHtR; P < 0.05 for non-linearity), and LBW was linked with lower BMI, smaller WC, and larger WHR and WHtR. An excess risk of T2DM was observed for LBW (<2500 g) versus birth weight 2500-3499 g since baseline (hazard ratio [HR] 1.17; 95% confidence interval [CI] 0.92-1.49) and since birth (HR 1.29; 95% CI 1.07-1.54), whereas the HRs for hypertension since baseline and birth were 1.13 (95% CI 1.01-1.27) and 1.20 (95% CI 1.11-1.30), respectively. The risk of the diseases decreased as birth weight increased up to ~4000 g; further increases in birth weight did not convey additional benefits. CONCLUSION: The results suggest that LBW, an index of poor intrauterine nutrition, may affect health risks later in life in the Chinese population.


Assuntos
Peso ao Nascer/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Hipertensão/fisiopatologia , Obesidade/fisiopatologia , Adulto , Grupo com Ancestrais do Continente Asiático , Pressão Sanguínea/fisiologia , Pesos e Medidas Corporais , China , Diabetes Mellitus Tipo 2/etnologia , Feminino , Inquéritos Epidemiológicos/métodos , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , Obesidade/etnologia , Estudos Prospectivos , Fatores de Risco
19.
Gastroenterology ; 156(5): 1455-1466, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30529582

RESUMO

BACKGROUND & AIMS: Genome-wide association studies (GWASs) have associated approximately 50 loci with risk of colorectal cancer (CRC)-nearly one third of these loci were initially associated with CRC in studies conducted in East Asian populations. We conducted a GWAS of East Asians to identify CRC risk loci and evaluate the generalizability of findings from GWASs of European populations to Asian populations. METHODS: We analyzed genetic data from 22,775 patients with CRC (cases) and 47,731 individuals without cancer (controls) from 14 studies in the Asia Colorectal Cancer Consortium. First, we performed a meta-analysis of 7 GWASs (10,625 cases and 34,595 controls) and identified 46,554 promising risk variants for replication by adding them to the Multi-Ethnic Global Array (MEGA) for genotype analysis in 6445 cases and 7175 controls. These data were analyzed, along with data from an additional 5705 cases and 5961 controls genotyped using the OncoArray. We also obtained data from 57,976 cases and 67,242 controls of European descent. Variants at identified risk loci were functionally annotated and evaluated in correlation with gene expression levels. RESULTS: A meta-analyses of all samples from people of Asian descent identified 13 loci and 1 new variant at a known locus (10q24.2) associated with risk of CRC at the genome-wide significance level of P < 5 × 10-8. We did not perform experiments to replicate these associations in additional individuals of Asian ancestry. However, the lead risk variant in 6 of these loci was also significantly associated with risk of CRC in European descendants. A strong association (44%-75% increase in risk per allele) was found for 2 low-frequency variants: rs201395236 at 1q44 (minor allele frequency, 1.34%) and rs77969132 at 12p11.21 (minor allele frequency, 1.53%). For 8 of the 13 associated loci, the variants with the highest levels of significant association were located inside or near the protein-coding genes L1TD1, EFCAB2, PPP1R21, SLCO2A1, HLA-G, NOTCH4, DENND5B, and GNAS. For other intergenic loci, we provided evidence for the possible involvement of the genes ALDH7A1, PRICKLE1, KLF5, WWOX, and GLP2R. We replicated findings for 41 of 52 previously reported risk loci. CONCLUSIONS: We showed that most of the risk loci previously associated with CRC risk in individuals of European descent were also associated with CRC risk in East Asians. Furthermore, we identified 13 loci significantly associated with risk for CRC in Asians. Many of these loci contained genes that regulate the immune response, Wnt signaling to ß-catenin, prostaglandin E2 catabolism, and cell pluripotency and proliferation. Further analyses of these genes and their variants is warranted, particularly for the 8 loci for which the lead CRC risk variants were not replicated in persons of European descent.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Loci Gênicos , Polimorfismo de Nucleotídeo Único , Ásia/epidemiologia , Estudos de Casos e Controles , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/imunologia , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Fenótipo , Medição de Risco , Fatores de Risco
20.
Int J Cancer ; 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30499135

RESUMO

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer aetiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5,183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ]= 1.08, 95%CI= 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer. This article is protected by copyright. All rights reserved.

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