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1.
BMJ Open ; 10(12): e039489, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277282

RESUMO

PURPOSE: The veterans administration diabetes risk (VADR) cohort facilitates studies on temporal and geographic patterns of pre-diabetes and diabetes, as well as targeted studies of their predictors. The cohort provides an infrastructure for examination of novel individual and community-level risk factors for diabetes and their consequences among veterans. This cohort also establishes a baseline against which to assess the impact of national or regional strategies to prevent diabetes in veterans. PARTICIPANTS: The VADR cohort includes all 6 082 018 veterans in the USA enrolled in the veteran administration (VA) for primary care who were diabetes-free as of 1 January 2008 and who had at least two diabetes-free visits to a VA primary care service at least 30 days apart within any 5-year period since 1 January 2003, or veterans subsequently enrolled and were diabetes-free at cohort entry through 31 December 2016. Cohort subjects were followed from the date of cohort entry until censure defined as date of incident diabetes, loss to follow-up of 2 years, death or until 31 December 2018. FINDINGS TO DATE: The incidence rate of type 2 diabetes in this cohort of over 6 million veterans followed for a median of 5.5 years (over 35 million person-years (PY)) was 26 per 1000 PY. During the study period, 8.5% of the cohort were lost to follow-up and 17.7% died. Many demographic, comorbidity and other clinical variables were more prevalent among patients with incident diabetes. FUTURE PLANS: This cohort will be used to study community-level risk factors for diabetes, such as attributes of the food environment and neighbourhood socioeconomic status via geospatial linkage to residence address information.

2.
Gastroenterology ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058866

RESUMO

BACKGROUND AND AIMS: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. METHODS: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted. RESULTS: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis. CONCLUSIONS: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.

3.
Am J Ind Med ; 63(9): 741-754, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32474961

RESUMO

BACKGROUND: While international agreement supports a causal relationship of benzene exposure with acute myeloid leukemia, there is debate about benzene and lymphoid neoplasm risks. METHODS: In a case-cohort study with follow-up of 110 631 Chinese workers during 1972-1999, we evaluated benzene exposure-response for non-Hodgkin lymphoma (NHL), lymphoid leukemias (LL), acute lymphocytic leukemia (ALL), and total lymphoid neoplasms (LN). We estimated benzene exposures using state-of-the-art hierarchical modeling of occupational factors calibrated with historical routine measurements and evaluated cumulative exposure-response using Cox regression. RESULTS: NHL and other specified LN were increased in exposed vs unexposed workers. However, there was no evidence of exposure-response for NHL or other specified LN. Based on a linear exposure-response, relative risks at 100 parts per million-years (RR at 100 ppm-years) for cumulative benzene exposure using a 2-year lag (exposure at least 2 years before the time at risk) were 1.05 for NHL (95 percent confidence interval (CI) = 0.97, 1.27; 32 cases), 1.11 for LL (95% CI < 0, 1.66; 12 cases), 1.21 for ALL (95% CI < 0, 3.53; 10 cases), and 1.02 for total LN (95% CI < 0, 1.16; 49 cases). No statistically significant exposure-response trends were apparent for these LN for 2 to <10-year or ≥10-year lags. NHL risks were not significantly modified by sex, age, or year at first exposure, attained age, or time since exposure. CONCLUSION: Given the study strengths and limitations, we found little evidence of exposure-response for benzene and NHL, LL, ALL, or total LN, although NHL and other specified LN were increased in exposed vs unexposed individuals.

4.
ISME J ; 14(7): 1639-1650, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32210364

RESUMO

Little is known regarding the impact of immigrant acculturation on the gut microbiome. We characterized differences in the gut microbiome between racially/ethnically diverse US immigrant and US-born groups, and determined the impact of dietary acculturation on the microbiome. Stool samples were collected from 863 US residents, including US-born (315 White, 93 Black, 40 Hispanic) and foreign-born (105 Hispanic, 264 Korean) groups. We determined dietary acculturation from dissimilarities based on food frequency questionnaires, and used 16S rRNA gene sequencing to characterize the microbiome. Gut microbiome composition differed across study groups, with the largest difference between foreign-born Koreans and US-born Whites, and significant differences also observed between foreign-born and US-born Hispanics. Differences in sub-operational taxonomic unit (s-OTU) abundance between foreign-born and US-born groups tended to be distinct from differences between US-born groups. Bacteroides plebeius, a seaweed-degrading bacterium, was strongly enriched in foreign-born Koreans, while Prevotella copri and Bifidobacterium adolescentis were strongly enriched in foreign-born Koreans and Hispanics, compared with US-born Whites. Dietary acculturation in foreign-born participants was associated with specific s-OTUs, resembling abundance in US-born Whites; e.g., a Bacteroides plebeius s-OTU was depleted in highly diet-acculturated Koreans. In summary, we observed that US nativity is a determinant of the gut microbiome in a US resident population. Dietary acculturation may result in loss of native species in immigrants, though further research is necessary to explore whether acculturation-related microbiome alterations have consequences for immigrant health.

5.
PLoS One ; 15(1): e0226972, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31914160

RESUMO

Mounting evidence indicates that coffee, a commonly consumed beverage worldwide, is inversely associated with various chronic diseases and overall mortality. Few studies have evaluated the effect of coffee drinking on telomere length, a biomarker of chromosomal integrity, and results have been inconsistent. Understanding this association may provide mechanistic insight into associations of coffee with health. The aim of our study was to test the hypothesis that heavier coffee intake is associated with greater likelihood of having above-median telomere length. We evaluated the cross-sectional association between coffee intake and relative telomere length using data from 1,638 controls from four previously conducted case-control studies nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Coffee intake was assessed using a food frequency questionnaire, and relative telomere length was measured from buffy-coat, blood, or buccal cells. We used unconditional logistic regression models to generate multivariable-adjusted, study-specific odds ratios for the association between coffee intake and relative telomere length. We then conducted a random-effects meta-analysis to determine summary odds ratios. We found that neither summary continuous (OR = 1.01, 95% CI = 0.99-1.03) nor categorical (OR <3 cups/day vs. none = 1.37, 95% CI = 0.71-2.65; OR ≥3 cups/day vs. none = 1.47, 95% CI = 0.81-2.66) odds ratio estimates of coffee drinking and relative telomere length were statistically significant. However, in the largest of the four contributing studies, moderate (<3 cups/day) and heavy coffee drinkers (≥3 cups/day) were 2.10 times (95% CI = 1.25, 3.54) and 1.93 times as likely (95% CI = 1.17, 3.18) as nondrinkers to have above-median telomere length, respectively. In conclusion, we found no evidence that coffee drinking is associated with telomere length. Thus, it is unlikely that telomere length plays a role in potential coffee-disease associations.


Assuntos
Cafeína/farmacologia , Café , Homeostase do Telômero/efeitos dos fármacos , Idoso , Café/metabolismo , Neoplasias Colorretais/prevenção & controle , Estudos Transversais , Feminino , Humanos , Neoplasias Pulmonares/prevenção & controle , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/prevenção & controle , Neoplasias da Próstata/prevenção & controle
6.
Int J Epidemiol ; 49(1): 25-35, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31289812

RESUMO

BACKGROUND: Ambient air pollution is a modifiable risk factor for cardiovascular disease, yet uncertainty remains about the size of risks at lower levels of fine particulate matter (PM2.5) exposure which now occur in the USA and elsewhere. METHODS: We investigated the relationship of ambient PM2.5 exposure with cause-specific cardiovascular disease mortality in 565 477 men and women, aged 50 to 71 years, from the National Institutes of Health-AARP Diet and Health Study. During 7.5 x 106 person-years of follow up, 41 286 cardiovascular disease deaths, including 23 328 ischaemic heart disease (IHD) and 5894 stroke deaths, were ascertained using the National Death Index. PM2.5 was estimated using a hybrid land use regression (LUR) geostatistical model. Multivariate Cox regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CI). RESULTS: Each increase of 10 µg/m3 PM2.5 (overall range, 2.9-28.0 µg/m3) was associated, in fully adjusted models, with a 16% increase in mortality from ischaemic heart disease [hazard ratio (HR) 1.16; 95% CI 1.09-1.22] and a 14% increase in mortality from stroke (HR 1.14; CI 1.02-1.27). Compared with PM2.5 exposure <8 µg/m3 (referent), risks for CVD were increased in relation to PM2.5 exposures in the range of 8-12 µg/m3 (CVD: HR 1.04; 95% CI 1.00-1.08), in the range 12-20 µg/m3 (CVD: HR 1.08; 95% CI 1.03-1.13) and in the range 20+ µg/m3 (CVD: HR 1.19; 95% CI 1.10-1.28). Results were robust to alternative approaches to PM2.5 exposure assessment and statistical analysis. CONCLUSIONS: Long-term exposure to fine particulate air pollution is associated with ischaemic heart disease and stroke mortality, with excess risks occurring in the range of and below the present US long-term standard for ambient exposure to PM2.5 (12 µg/m3), indicating the need for continued improvements in air pollution abatement for CVD prevention.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Doenças Cardiovasculares/mortalidade , Exposição Ambiental/análise , Material Particulado/efeitos adversos , Idoso , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Material Particulado/análise , Modelos de Riscos Proporcionais , Fatores de Risco , Estados Unidos/epidemiologia
7.
Clin Gastroenterol Hepatol ; 18(12): 2752-2759.e2, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31622737

RESUMO

BACKGROUND & AIMS: The incidence of colorectal cancer (CRC) is increasing in individuals younger than 50 years, who do not usually undergo screening if they are of average risk. We sought to identify risk factors for CRC in this population. METHODS: We compared sociodemographic and medical characteristics of patients who received a diagnosis of CRC at an age of 18-49 years (early-onset) with patients who received a diagnosis of CRC at an age of 50 years or older (late-onset) and with age-matched, cancer-free individuals (controls) at a tertiary academic hospital. We collected data from all adult patients with a diagnosis of CRC from January 1, 2011 through April 3, 2017 from electronic health records. Associations with risk factors were assessed using univariable and multivariable logistic regression models. RESULTS: We identified 269 patients with early-onset CRC, 2802 with late-onset CRC, and 1122 controls. Compared with controls, patients with early-onset CRC were more likely to be male (odds ratio [OR], 1.87; 95% CI, 1.39-2.51), have inflammatory bowel disease (IBD) (3% vs 0.4% for controls; univariable P < .01), and have a family history of CRC (OR, 8.61; CI, 4.83-15.75). Prevalence values of well-established modifiable CRC risk factors, including obesity, smoking, and diabetes, were similar. Compared to patients with late-onset CRC, patients with early-onset CRC were more likely to be male (OR, 1.44; 95% CI, 1.11-1.87), black (OR, 1.73; 95% CI, 1.08-2.65) or Asian (OR, 2.60; 95% CI, 1.57-4.15), and have IBD (OR, 2.97; 95% CI, 1.16-6.63) or a family history of CRC (OR, 2.87; 95% CI, 1.89-4.25). Sensitivity analyses excluding IBD and family history of CRC showed comparable results. Early-onset CRC was more likely than late-onset disease to be detected in the left colon or rectum (75% vs 59%, P = .02) and at a late stage of tumor development (77% vs 62%, P = .01). CONCLUSIONS: In a retrospective study of patients with early-onset CRC vs late-onset CRC or no cancer, we identified non-modifiable risk factors, including sex, race, IBD, and family history of CRC, to be associated with early-onset CRC.

8.
Int J Cancer ; 146(3): 861-873, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31037736

RESUMO

Alcohol consumption is an established risk factor for colorectal cancer (CRC). However, while studies have consistently reported elevated risk of CRC among heavy drinkers, associations at moderate levels of alcohol consumption are less clear. We conducted a combined analysis of 16 studies of CRC to examine the shape of the alcohol-CRC association, investigate potential effect modifiers of the association, and examine differential effects of alcohol consumption by cancer anatomic site and stage. We collected information on alcohol consumption for 14,276 CRC cases and 15,802 controls from 5 case-control and 11 nested case-control studies of CRC. We compared adjusted logistic regression models with linear and restricted cubic splines to select a model that best fit the association between alcohol consumption and CRC. Study-specific results were pooled using fixed-effects meta-analysis. Compared to non-/occasional drinking (≤1 g/day), light/moderate drinking (up to 2 drinks/day) was associated with a decreased risk of CRC (odds ratio [OR]: 0.92, 95% confidence interval [CI]: 0.88-0.98, p = 0.005), heavy drinking (2-3 drinks/day) was not significantly associated with CRC risk (OR: 1.11, 95% CI: 0.99-1.24, p = 0.08) and very heavy drinking (more than 3 drinks/day) was associated with a significant increased risk (OR: 1.25, 95% CI: 1.11-1.40, p < 0.001). We observed no evidence of interactions with lifestyle risk factors or of differences by cancer site or stage. These results provide further evidence that there is a J-shaped association between alcohol consumption and CRC risk. This overall pattern was not significantly modified by other CRC risk factors and there was no effect heterogeneity by tumor site or stage.


Assuntos
Neoplasias Colorretais/etiologia , Etanol/efeitos adversos , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Fatores de Risco
9.
Int J Cancer ; 146(2): 363-372, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31209889

RESUMO

Interindividual differences in DNA repair systems may play a role in modulating the individual risk of developing colorectal cancer. To better ascertain the role of DNA repair gene polymorphisms on colon and rectal cancer risk individually, we evaluated 15,419 single nucleotide polymorphisms (SNPs) within 185 DNA repair genes using GWAS data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), which included 8,178 colon cancer, 2,936 rectum cancer cases and 14,659 controls. Rs1800734 (in MLH1 gene) was associated with colon cancer risk (p-value = 3.5 × 10-6 ) and rs2189517 (in RAD51B) with rectal cancer risk (p-value = 5.7 × 10-6 ). The results had statistical significance close to the Bonferroni corrected p-value of 5.8 × 10-6 . Ninety-four SNPs were significantly associated with colorectal cancer risk after Binomial Sequential Goodness of Fit (BSGoF) procedure and confirmed the relevance of DNA mismatch repair (MMR) and homologous recombination pathways for colon and rectum cancer, respectively. Defects in MMR genes are known to be crucial for familial form of colorectal cancer but our findings suggest that specific genetic variations in MLH1 are important also in the individual predisposition to sporadic colon cancer. Other SNPs associated with the risk of colon cancer (e.g., rs16906252 in MGMT) were found to affect mRNA expression levels in colon transverse and therefore working as possible cis-eQTL suggesting possible mechanisms of carcinogenesis.


Assuntos
Neoplasias do Colo/genética , Reparo do DNA/genética , Predisposição Genética para Doença , Neoplasias Retais/genética , Adulto , Idoso , Variação Biológica da População/genética , Carcinogênese/genética , Estudos de Casos e Controles , Colo/patologia , Neoplasias do Colo/patologia , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Retais/patologia , Reto/patologia , Sistema de Registros/estatística & dados numéricos , Medição de Risco , Proteínas Supressoras de Tumor/genética , Adulto Jovem
10.
BMJ Open Gastroenterol ; 6(1): e000339, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31875139

RESUMO

Objective: 'Environmental' factors associated with colorectal cancer (CRC) risk include modifiable and non-modifiable variables. Whether those with different non-modifiable baseline risks will benefit similarly from reducing their modifiable CRC risks remains unclear. Design: Using 7945 cases and 8893 controls from 11 population-based studies, we combined 17 risk factors to characterise the overall environmental predisposition to CRC (environmental risk score (E-score)). We estimated the absolute risks (ARs) of CRC of 10 and 30 years across E-score using incidence-rate data from the Surveillance, Epidemiology, and End Results programme. We then combined the modifiable risk factors and estimated ARs across the modifiable risk score, stratified by non-modifiable risk profile based on genetic predisposition, family history and height. Results: Higher E-score was associated with increased CRC risk (ORquartile, 1.33; 95% CI 1.30 to 1.37). Across E-scores, 30-year ARs of CRC increased from 2.5% in the lowest quartile (Q1) to 5.9% in the highest (Q4) quartile for men, and from 2.1% to 4.5% for women. The modifiable risk score had a stronger association in those with high non-modifiable risk (relative excess risk due to interaction=1.2, 95% CI 0.5 to 1.9). For those in Q4 of non-modifiable risk, a decrease in modifiable risk reduced 30-year ARs from 8.9% to 3.4% for men and from 6.0% to 3.2% for women, a level lower or comparable to the average population risk. Conclusions: Changes in modifiable risk factors may result in a substantial decline in CRC risk in both sexes. Those with high inherited risk may reap greater benefit from lifestyle modifications. Our results suggested comprehensive evaluation of environmental factors may facilitate CRC risk stratification.

11.
Cancer Epidemiol ; 63: 101615, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31586822

RESUMO

BACKGROUND: Tobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk. METHODS: We analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models. RESULTS: Without adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR<10 years vs. ≥30 years: 1.64, 95% CI: 1.35, 1.97). However, the observed association between age at starting tobacco use and HNC risk became null after adjusting for tobacco packyears (OR<10 years vs. ≥30 years: 0.97, 95% CI: 0.80, 1.19). In the stratified analyses on HNC subsites by tobacco packyears or years since quitting, no difference in the association between age at start and HNC risk was observed. CONCLUSIONS: Results from this pooled analysis suggest that increased HNC risks observed with earlier age at starting tobacco smoking are largely due to longer duration and higher cumulative tobacco exposures.


Assuntos
Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/etiologia , Tabaco/efeitos adversos , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
12.
Gut ; 68(12): 2179-2185, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31488504

RESUMO

OBJECTIVE: Early-onset colorectal cancer (CRC) is increasing in the USA despite rapid declines in older ages. Similar patterns are reported in Australia and Canada, but a comprehensive global analysis of contemporary data is lacking. DESIGN: We extracted long-term data from Cancer Incidence in Five Continents and supplemental sources to report on worldwide CRC incidence rates and trends by age (20-49 years and ≥50 years) through diagnosis year 2012 or beyond (Australia, Finland, New Zealand, Norway, Sweden, USA). RESULTS: During 2008-2012, age-standardised CRC incidence rates in adults <50 ranged from 3.5 per 100 000 (95% CI 3.2 to 3.9) in India (Chennai) to 12.9 (95% CI 12.6 to 13.3) in Korea. During the most recent decade of available data, incidence in adults <50 was stable in 14 of 36 countries; declined in Austria, Italy and Lithuania; and increased in 19 countries, nine of which had stable or declining trends in older adults (Australia, Canada, Denmark, Germany, New Zealand, Slovenia, Sweden, UK and USA). In Cyprus, Netherlands and Norway, inclines in incidence in young adults were twice as rapid as those in older adults (eg, Norway average annual per cent change (AAPC), 1.9 (95% CI 1.4 to 2.5) vs 0.5 (95% CI 0.3 to 0.7)). Among most high-income countries with long-term data, the uptick in early-onset disease began in the mid-1990s. The steepest increases in young adults were in Korea (AAPC, 4.2 (95% CI 3.4 to 5.0)) and New Zealand (AAPC, 4.0 (95% CI 2.1 to 6.0)). CONCLUSION: CRC incidence increased exclusively in young adults in nine high-income countries spanning three continents, potentially signalling changes in early-life exposures that influence large bowel carcinogenesis.


Assuntos
Neoplasias Colorretais/epidemiologia , Previsões , Adulto , Distribuição por Idade , Idade de Início , Feminino , Seguimentos , Saúde Global , Humanos , Incidência , Masculino , Estudos Retrospectivos , Adulto Jovem
13.
Sci Rep ; 9(1): 10039, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31296925

RESUMO

Incense burning is common worldwide and produces environmental toxicants that may influence health; however, biologic effects have been little studied. In 303 Emirati adults, we tested the hypothesis that incense use is linked to compositional changes in the oral microbiota that can be potentially significant for health. The oral microbiota was assessed by amplification of the bacterial 16S rRNA gene from mouthwash samples. Frequency of incense use was ascertained through a questionnaire and examined in relation to overall oral microbiota composition (PERMANOVA analysis), and to specific taxon abundances, by negative binomial generalized linear models. We found that exposure to incense burning was associated with higher microbial diversity (p < 0.013) and overall microbial compositional changes (PERMANOVA, p = 0.003). Our study also revealed that incense use was associated with significant changes in bacterial abundances (i.e. depletion of the dominant taxon Streptococcus), even in occasional users (once/week or less) implying that incense use impacts the oral microbiota even at low exposure levels. In summary, this first study suggests that incense burning alters the oral microbiota, potentially serving as an early biomarker of incense-related toxicities and related health consequences. Although a common indoor air pollutant, guidelines for control of incense use have yet to be developed.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Microbiota/efeitos dos fármacos , Boca/microbiologia , Odorantes/análise , Fumaça/análise , Adulto , Feminino , Humanos , Masculino , Microbiota/genética , Antissépticos Bucais , RNA Ribossômico 16S/genética , Inquéritos e Questionários
14.
Am J Respir Crit Care Med ; 200(8): 1022-1031, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31051079

RESUMO

Rationale: Many studies have linked short-term exposure to ozone (O3) with morbidity and mortality, but epidemiologic evidence of associations between long-term O3 exposure and mortality is more limited.Objectives: To investigate associations of long-term (annual or warm season average of daily 8-h maximum concentrations) O3 exposure with all-cause and cause-specific mortality in the NIH-AARP Diet and Health Study, a large prospective cohort of U.S. adults with 17 years of follow-up from 1995 to 2011.Methods: The cohort (n = 548,780) was linked to census tract-level estimates for O3. Associations between long-term O3 exposure (averaged values from 2002 to 2010) and multiple causes of death were evaluated using multivariate Cox proportional hazards models, adjusted for individual- and census tract-level covariates, and potentially confounding copollutants and temperature.Measurements and Main Results: Long-term annual average exposure to O3 was significantly associated with deaths caused by cardiovascular disease (per 10 ppb; hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01-1.06), ischemic heart disease (HR, 1.06; 95% CI, 1.02-1.09), respiratory disease (HR, 1.04; 95% CI, 1.00-1.09), and chronic obstructive pulmonary disease (HR, 1.09; 95% CI, 1.03-1.15) in single-pollutant models. The results were robust to alternative models and adjustment for copollutants (fine particulate matter and nitrogen dioxide), although some evidence of confounding by temperature was observed. Significantly elevated respiratory disease mortality risk associated with long-term O3 exposure was found among those living in locations with high temperature (Pinteraction < 0.05).Conclusions: This study found that long-term exposure to O3 is associated with increased risk for multiple causes of mortality, suggesting that establishment of annual and/or seasonal federal O3 standards is needed to more adequately protect public health from ambient O3 exposures.


Assuntos
Poluição do Ar/efeitos adversos , Causas de Morte , Exposição Ambiental/efeitos adversos , Oxidantes Fotoquímicos/efeitos adversos , Ozônio/efeitos adversos , Doenças Respiratórias/induzido quimicamente , Doenças Respiratórias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
15.
Circulation ; 139(15): 1766-1775, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30700142

RESUMO

BACKGROUND: Recent experimental evidence suggests that nutritional supplementation can blunt adverse cardiopulmonary effects induced by acute air pollution exposure. However, whether usual individual dietary patterns can modify the association between long-term air pollution exposure and health outcomes has not been previously investigated. We assessed, in a large cohort with detailed diet information at the individual level, whether a Mediterranean diet modifies the association between long-term exposure to ambient air pollution and cardiovascular disease mortality risk. METHODS: The National Institutes of Health-American Association for Retired Persons Diet and Health Study, a prospective cohort (N=548 845) across 6 states and 2 cities in the United States and with a follow-up period of 17 years (1995-2011), was linked to estimates of annual average exposures to fine particulate matter and nitrogen dioxide at the residential census-tract level. The alternative Mediterranean Diet Index, which uses a 9-point scale to assess conformity with a Mediterranean-style diet, was constructed for each participant from information in cohort baseline dietary questionnaires. We evaluated mortality risks for cardiovascular disease, ischemic heart disease, cerebrovascular disease, or cardiac arrest associated with long-term air pollution exposure. Effect modification of the associations between exposure and the mortality outcomes by alternative Mediterranean Diet Index was examined via interaction terms. RESULTS: For fine particulate matter, we observed elevated and significant associations with cardiovascular disease (hazard ratio [HR] per 10 µg/m3, 1.13; 95% CI, 1.08-1.18), ischemic heart disease (HR, 1.16; 95% CI, 1.10-1.23), and cerebrovascular disease (HR, 1.15; 95% CI, 1.03-1.28). For nitrogen dioxide, we found significant associations with cardiovascular disease (HR per 10 ppb, 1.06; 95% CI, 1.04-1.08) and ischemic heart disease (HR, 1.08; 95% CI, 1.05-1.11). Analyses indicated that Mediterranean diet modified these relationships, as those with a higher alternative Mediterranean Diet Index score had significantly lower rates of cardiovascular disease mortality associated with long-term air pollution exposure ( P-interaction<0.05). CONCLUSIONS: A Mediterranean diet reduced cardiovascular disease mortality risk related to long-term exposure to air pollutants in a large prospective US cohort. Increased consumption of foods rich in antioxidant compounds may aid in reducing the considerable disease burden associated with ambient air pollution.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Dieta Saudável , Dieta Mediterrânea , Exposição Ambiental/efeitos adversos , Material Particulado/efeitos adversos , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Nutritivo , Prognóstico , Estudos Prospectivos , Fatores de Proteção , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia
16.
Cancer Epidemiol Biomarkers Prev ; 28(4): 731-740, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30733306

RESUMO

BACKGROUND: Human microbiota have many functions that could contribute to cancer initiation and/or progression at local sites, yet the relation of the lung microbiota to lung cancer prognosis has not been studied. METHODS: In a pilot study, 16S rRNA gene sequencing was performed on paired lung tumor and remote normal samples from the same lobe/segment in 19 patients with non-small cell lung cancer (NSCLC). We explored associations of tumor or normal tissue microbiome diversity and composition with recurrence-free (RFS) and disease-free survival (DFS), and compared microbiome diversity and composition between paired tumor and normal samples. RESULTS: Higher richness and diversity in normal tissue were associated with reduced RFS (richness P = 0.08, Shannon index P = 0.03) and DFS (richness P = 0.03, Shannon index P = 0.02), as was normal tissue overall microbiome composition (Bray-Curtis P = 0.09 for RFS and P = 0.02 for DFS). In normal tissue, greater abundance of family Koribacteraceae was associated with increased RFS and DFS, whereas greater abundance of families Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae were associated with reduced RFS or DFS (P < 0.05). Tumor tissue diversity and overall composition were not associated with RFS or DFS. Tumor tissue had lower richness and diversity (P ≤ 0.0001) than paired normal tissue, though overall microbiome composition did not differ between the paired samples. CONCLUSIONS: We demonstrate, for the first time, a potential relationship between the normal lung microbiota and lung cancer prognosis, which requires confirmation in a larger study. IMPACT: Definition of bacterial biomarkers of prognosis may lead to improved survival outcomes for patients with lung cancer.


Assuntos
Neoplasias Pulmonares/patologia , Microbiota/genética , Idoso , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino
17.
Prim Care Diabetes ; 13(1): 49-56, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30025678

RESUMO

BACKGROUND: Exposure to antibiotics may increase the risk of type 2 diabetes. Veterans are at increased risk for diabetes and for exposure to antibiotics. OBJECTIVE: To determine the impact of antibiotic exposure for risk of diabetes. DESIGN: Retrospective cohort study. PARTICIPANTS: Veterans at the New York Harbor Healthcare System enrolled in primary care, 2004-2014, with ≥2 glycosylated hemoglobin test results <6.5%. MAIN MEASURES: The primary exposure was any antimicrobial prescribed >6 months prior to the date of diabetes diagnosis, loss to follow-up, death, or the end of the study, measured as the number of courses of antimicrobial prescriptions filled and the mean daily dose (MDD). The primary outcome was incident diagnosis of diabetes through 2014, defined ≥2 ICD-9 codes for diabetes or ≥2 prescriptions of diabetes medications, other than metformin. Cox proportional hazards regression was used to model antimicrobial medications, demographic and anthropometric measures, and comorbid cardiovascular conditions to incident diabetes. Models incorporated time varying covariates of antimicrobial medication and MDD to analyze associations by antimicrobial class. KEY RESULTS: Among 14,361 Veterans, 9922 (69.1%) were prescribed any antimicrobial medication during the study period. 1413 (9.8%) individuals developed type 2 diabetes. Increased risk of diabetes was associated with >1 prescription (HR 1.13 [1.01-1.26]) compared to none. Time varying analysis of the total number of cumulative courses prescribed showed increased diabetes risk for cephalosporin (HR 1.17 [1.04-1.31]), macrolide (HR 1.08 [1.03-1.13]) and penicillin (HR 1.05 [1.02-1.07]). MDD showed increased risk per 100-unit (mg) increase in antibiotic exposure from (HR 1.05 [1.02-1.08]) for sulfonamide to (HR 1.70 [1.51-1.92]) for cephalosporin. CONCLUSION: Any and repeated exposure to certain antibiotics may increase diabetes risk among Veterans. Results from this study add to the growing evidence suggesting that antibiotic exposure increases risk for diabetes. Antibiotic stewardship may be enhanced by better understanding this risk, and may lower the incidence of diabetes in populations at risk.


Assuntos
Antibacterianos/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Saúde dos Veteranos , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Prescrições de Medicamentos , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
18.
Clin Gastroenterol Hepatol ; 17(8): 1561-1570.e3, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30476588

RESUMO

BACKGROUND & AIMS: Red and processed meat intake is associated with colorectal cancer (CRC) incidence, but it is not clear if intake is associated with patient survival after diagnosis. METHODS: We pooled data from 7627 patients with stage I-IV CRC from 10 studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of intake of red and processed meat before diagnosis with overall and CRC-specific survival. RESULTS: Among 7627 patients with CRC, 2338 died, including 1576 from CRC, over a median follow-up time of 5.1 years. In multivariable-adjusted analyses, higher intake of red or processed meat was not associated with overall survival of patients with stage I-III CRC: Q4 vs Q1 red meat hazard ratio [HR], 1.08 (95% CI, 0.93-1.26) and Q4 vs Q1 processed meat HR, 1.10 (95% CI, 0.93-1.32) or with CRC-specific survival: Q4 vs Q1 red meat HR, 1.09 (95% CI, 0.89-1.33) and Q4 vs Q1 processed meat HR, 1.11 (95% CI, 0.87-1.42). Results were similar for patients with stage IV CRC. However, patients with stage I-III CRC who reported an intake of processed meat above the study-specific medians had a higher risk of death from any cause (HR, 1.12; 95% CI, 1.01-1.25) than patients who reported eating at or less than the median. CONCLUSION: In this large consortium of CRC patient cohorts, intake of red and processed meat before a diagnosis of CRC was not associated with shorter survival time after diagnosis, although a possible weak adverse association cannot be excluded. Studies that evaluate dietary data from several time points before and after cancer diagnosis are required to confirm these findings.


Assuntos
Neoplasias Colorretais/epidemiologia , Dieta , Comportamento Alimentar/fisiologia , Produtos da Carne/efeitos adversos , Carne Vermelha/efeitos adversos , Medição de Risco/métodos , Idoso , Neoplasias Colorretais/etiologia , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Prognóstico , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
19.
J Natl Cancer Inst ; 111(5): 465-474, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30520970

RESUMO

BACKGROUND: There is international consensus that benzene exposure is causally related to acute myeloid leukemia (AML), and more recent evidence of association with myelodysplastic syndromes (MDS). However, there are uncertainties about the exposure response, particularly risks by time since exposure and age at exposure. METHODS: In a case-cohort study in 110 631 Chinese workers followed up during 1972-1999 we evaluated combined MDS/AML (n = 44) and chronic myeloid leukemia (n = 18). We estimated benzene exposures using hierarchical modeling of occupational factors calibrated with historical routine measurements, and evaluated exposure response for cumulative exposure and average intensity using Cox regression; P values were two-sided. RESULTS: Increased MDS/AML risk with increasing cumulative exposure in our a priori defined time window (2 to <10 years) before the time at risk was suggested (Ptrend = 08). For first exposure (within the 2 to <10-year window) before age 30 years, the exposure response was stronger (P = .004) with rate ratios of 1.12 (95% confidence interval [CI] = 0.27 to 4.29), 5.58 (95% CI = 1.65 to 19.68), and 4.50 (95% CI = 1.22 to 16.68) for cumulative exposures of more than 0 to less than 40, 40 to less than 100, and at least 100 ppm-years, respectively, compared with no exposure. There was little evidence of exposure response after at least 10 years (Ptrend = .94), regardless of age at first exposure. Average intensity results were generally similar. The risk for chronic myeloid leukemia was increased in exposed vs unexposed workers, but appeared to increase and then decrease with increasing exposure. CONCLUSION: For myeloid neoplasms, the strongest effects were apparent for MDS/AML arising within 10 years of benzene exposure and for first exposure in the 2 to less than 10-year window before age 30 years.


Assuntos
Benzeno/toxicidade , Leucemia Mieloide Aguda/induzido quimicamente , Síndromes Mielodisplásicas/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Fatores Etários , China/epidemiologia , Estudos de Coortes , Intervalos de Confiança , Humanos , Leucemia Mieloide Aguda/epidemiologia , Síndromes Mielodisplásicas/epidemiologia , Exposição Ocupacional/estatística & dados numéricos , Modelos de Riscos Proporcionais , Risco , Fatores de Tempo , Incerteza
20.
PLoS One ; 13(10): e0206519, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30379922

RESUMO

BACKGROUND: High levels of serum leptin and low levels of serum adiponectin are strongly correlated with obesity, a well-established risk factor for colorectal cancer (CRC). Growing evidence suggests that dysregulation of leptin and adiponectin levels may play an etiological role in colorectal carcinogenesis. We evaluated 20 candidate variants in 4 genes previously shown to alter serum leptin and adiponectin levels for associations with obesity (BMI>30 kg/m2) and CRC risk. METHODS: We analyzed 6,246 CRC cases and 7,714 population-based controls from 11 studies within the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations of each variant with obesity or CRC were evaluated using multivariate logistic regression models stratified by sex and adjusted for age, a study variable, and the first three principal components of genetic ancestry. Gene-specific False Discovery Rate (FDR)-adjusted p-values <0.05 denoted statistical significance. RESULTS: Two variants in the leptin gene showed statistically significant associations with CRC among women: LEP rs2167270 (OR = 1.13, 95% CI: 1.06-1.21) and LEP rs4731426 (OR = 1.09, 95% CI: 1.02-1.17). These associations remained significant after adjustment for obesity, suggesting that leptin SNPs may influence CRC risk independent of obesity. We observed statistically significant interactions of the leptin variants with hormone replacement therapy (HRT) for CRC risk; these variant associations were strengthened when analyses were restricted to post-menopausal women with low estrogen exposure, as estimated by 'never use' of HRT and/or non-obese BMI. No variants were associated with CRC among men. CONCLUSIONS: Leptin gene variants may exhibit sex-specific associations with CRC risk. Endogenous and exogenous estrogen exposure may modify the association between these variants, leptin levels, and CRC risk.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Leptina/genética , Polimorfismo de Nucleotídeo Único , Adiponectina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias Colorretais/patologia , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
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