Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 92
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Int J Cancer ; 145(10): 2647-2660, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30737780

RESUMO

Benzene is considered a carcinogen, mostly based on evidence of causality for myeloid leukemia from high levels of exposure in occupational studies. We used United States Environmental Protection Agency National Ambient Toxics Assessment (NATA) estimates of low-level ambient benzene to examine potential associations for the general public between benzene exposure and risk of hematologic cancers. Exposure was estimated by linking participants' residential address to the NATA benzene estimates for that census tract. Among 115,996 American Cancer Society Cancer Prevention Study-II Nutrition cohort participants (52,554 men, 63,442 women), 2,595 were diagnosed with incident hematologic cancer between 1997 and 2013. Extended Cox regression modeling was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Among all participants, ambient benzene was positively associated with myelodysplastic syndromes (HR = 1.16, 95% CI: 1.01-1.33 per µg/m3 ) and T-cell lymphoma (HR = 1.29, 95% CI: 1.08-1.53 per µg/m3 ). Among men, ambient benzene was also positively associated with any hematologic malignancy (HR = 1.07, 95% CI: 1.01-1.15 per µg/m3 ) and follicular lymphoma (HR = 1.28, 95% CI: 1.09-1.50 per µg/m3 ). No significant associations were observed for women only, but associations were suggestive for MDS and T-cell lymphoma. It is possible that the NATA ambient benzene estimates are a better proxy for benzene exposure for men than women in this cohort. The results of this study support an association between ambient benzene and risk of hematologic malignancies, particularly MDS, T-cell lymphoma and follicular lymphoma. More research in large scale or pooled studies is needed to further explore these associations.

2.
Am J Epidemiol ; 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30325407

RESUMO

Social isolation is associated with higher mortality in studies of mostly white adults, yet associations among black adults is unclear. This prospective cohort study evaluated whether associations of social isolation with all-cause, cardiovascular disease and cancer mortality differ by race and sex. Adults enrolled into Cancer Prevention Study-II in 1982/1983 were followed for mortality through 2012 (n = 580,182). Sex- and race-specific multivariable-adjusted hazard ratios and 95% confidence intervals were estimated for associations of a five-point social isolation score with risk of death. Social isolation was associated with all-cause mortality in all subgroups (P-trend ≤ 0.005); for the most versus the least isolated, the hazard ratios (95% confidence intervals) were 2.34 (1.58, 3.46) and 1.60 (1.41, 1.82) among black and white men, respectively (P-interaction = 0.40), and 2.13 (1.44, 3.15) and 1.84 (1.68, 2.01) among black and white women, respectively (P-interaction = 0.89). The association did not differ between black men and women (P-interaction = 0.33) but was slightly stronger in white women than white men (P-interaction = 0.01). Social isolation was associated with cardiovascular disease mortality in each subgroup (P-trend < 0.03) but with cancer mortality only among whites (P-trend < 0.0001). Subgroup differences in the influence of specific social isolation components were identified. Identifying and intervening with socially isolated adults could improve health outcomes.

3.
Nat Commun ; 9(1): 4182, 2018 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-30305637

RESUMO

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10-54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10-19). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.

4.
Proc Natl Acad Sci U S A ; 115(38): 9592-9597, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30181279

RESUMO

Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição Ambiental/efeitos adversos , Carga Global da Doença/estatística & dados numéricos , Doenças não Transmissíveis/mortalidade , Material Particulado/toxicidade , Poluição do Ar/efeitos adversos , Teorema de Bayes , Estudos de Coortes , Saúde Global/estatística & dados numéricos , Humanos , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Tempo
5.
Am J Prev Med ; 55(3): 345-352, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30122215

RESUMO

INTRODUCTION: Secondhand smoke is known to have adverse effects on the lung and vascular systems in both children and adults. It is unknown if childhood exposure to secondhand smoke is associated with adult mortality. METHODS: The authors examined associations of childhood and adult secondhand smoke exposure with death from all causes, ischemic heart disease, stroke, and chronic obstructive pulmonary disease among 70,900 never smoking men and women, predominantly aged ≥50 years, from the Cancer Prevention Study-II Nutrition Cohort in 1992-1993. There were 25,899 participant deaths during follow-up through 2014. During 2016-2017, Cox proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios and 95% CIs. RESULTS: Childhood secondhand smoke exposure was not associated with all-cause mortality. However, childhood secondhand smoke (living with a smoker for 16-18 years during childhood) was associated with higher mortality from chronic obstructive pulmonary disease (hazard ratio=1.31, 95% CI=1.05, 1.65). Adult secondhand smoke exposure of ≥10 hours/week at enrollment was associated with a higher risk of all-cause (hazard ratio=1.09, 95% CI=1.04, 1.14); ischemic heart disease (hazard ratio=1.27, 95% CI=1.14, 1.42); stroke (hazard ratio=1.23, 95% CI=1.04, 1.45); and chronic obstructive pulmonary disease (hazard ratio=1.42, 95% CI=0.97, 2.09) mortality. CONCLUSIONS: These results suggest that childhood secondhand smoke exposure, as well as adult secondhand smoke exposure, increase the risk of chronic obstructive pulmonary disease death in adulthood. Consistent with previous studies, the results also show that adult secondhand smoke is meaningfully associated with higher mortality from vascular disease and all causes. Overall, these findings provide further evidence for reducing secondhand smoke exposure throughout life.

6.
Cancer Res ; 78(14): 4086-4096, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29735552

RESUMO

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086-96. ©2018 AACR.

7.
Lupus Sci Med ; 4(1): e000187, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29214033

RESUMO

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.

8.
Int J Epidemiol ; 46(6): 1814-1822, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29232439

RESUMO

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer. Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis. Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95). Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Receptores Estrogênicos/genética , Causalidade , Europa (Continente)/epidemiologia , Feminino , Variação Genética , Humanos , Análise da Randomização Mendeliana , Metanálise como Assunto , Polimorfismo de Nucleotídeo Único , Medição de Risco , Fatores de Risco , Análise de Sobrevida
9.
Environ Health Perspect ; 125(8): 087013, 2017 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-28886601

RESUMO

BACKGROUND: The International Agency for Research on Cancer classified both outdoor air pollution and airborne particulate matter as carcinogenic to humans (Group 1) for lung cancer. There may be associations with cancer at other sites; however, the epidemiological evidence is limited. OBJECTIVE: The aim of this study was to clarify whether ambient air pollution is associated with specific types of cancer other than lung cancer by examining associations of ambient air pollution with nonlung cancer death in the Cancer Prevention Study II (CPS-II). METHODS: Analysis included 623,048 CPS-II participants who were followed for 22 y (1982-2004). Modeled estimates of particulate matter with aerodynamic diameter <2.5µm (PM2.5) (1999-2004), nitrogen dioxide (NO2) (2006), and ozone (O3) (2002-2004) concentrations were linked to the participant residence at enrollment. Cox proportional hazards models were used to estimate associations per each fifth percentile-mean increment with cancer mortality at 29 anatomic sites, adjusted for individual and ecological covariates. RESULTS: We observed 43,320 nonlung cancer deaths. PM2.5 was significantly positively associated with death from cancers of the kidney {adjusted hazard ratio (HR) per 4.4 µg/m3=1.14 [95% confidence interval (CI): 1.03, 1.27]} and bladder [HR=1.13 (95% CI: 1.03, 1.23)]. NO2 was positively associated with colorectal cancer mortality [HR per 6.5 ppb=1.06 (95% CI: 1.02, 1.10). The results were similar in two-pollutant models including PM2.5 and NO2 and in three-pollutant models with O3. We observed no statistically significant positive associations with death from other types of cancer based on results from adjusted models. CONCLUSIONS: The results from this large prospective study suggest that ambient air pollution was not associated with death from most nonlung cancers, but associations with kidney, bladder, and colorectal cancer death warrant further investigation. https://doi.org/10.1289/EHP1249.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Neoplasias/mortalidade , Adulto , Poluentes Atmosféricos/análise , Humanos , Dióxido de Nitrogênio/análise , Ozônio , Material Particulado/análise , Modelos de Riscos Proporcionais , Fatores de Tempo
10.
Cancer Epidemiol Biomarkers Prev ; 26(7): 1071-1077, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28264874

RESUMO

Background: Cigarette price increases effectively prevent smoking initiation and reduce cigarette consumption among young smokers. However, the impact of cigarette prices on smoking cessation among older smokers is less clear, particularly for those aged 65 years and older, a group that is at highest risk of smoking-related disease and will almost double in the United States between 2012 and 2050.Methods: Biennial questionnaires administered between 1997 and 2013 assessed smoking status for 9,446 Cancer Prevention Study-II Nutrition Cohort participants who were ≥50 years old and lived in Washington, DC, and 48 states. For each interval between biennial questionnaires, change in price per pack and average price level per pack were calculated. The separate associations between these price variables and smoking cessation during the same time interval were determined.Results: In multivariable-adjusted models, each $1.00 price increase was associated with a 9% higher rate of quitting [rate ratio (RR) = 1.09; 95% confidence interval (CI), 1.04-1.14). Each $1.00 increase in average price was associated with a 6% higher rate of quitting (RR = 1.06; 95% CI, 1.02-1.10). The association with average price was strongest among smokers aged 65 years and older (RR = 1.07; 95% CI, 1.04-1.11) and, for price change, for smokers with no major prevalent disease (RR = 1.13; 95% CI, 1.07-1.19).Conclusions: These results suggest that increasing cigarette prices will promote quitting even among smokers aged 65 years and older.Impact: Increasing cigarette prices through higher taxes could reduce smoking rates among older adults and decrease risk of smoking-related cancers and diseases in this high-risk group. Cancer Epidemiol Biomarkers Prev; 26(7); 1071-7. ©2017 AACR.


Assuntos
Neoplasias/epidemiologia , Fumantes/estatística & dados numéricos , Abandono do Hábito de Fumar/estatística & dados numéricos , Prevenção do Hábito de Fumar/métodos , Fumar/epidemiologia , Produtos do Tabaco/economia , Fatores Etários , Idoso , Comércio/economia , Feminino , Seguimentos , Política de Saúde , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/prevenção & controle , Prevalência , Estudos Prospectivos , Fumar/efeitos adversos , Fumar/legislação & jurisprudência , Abandono do Hábito de Fumar/economia , Prevenção do Hábito de Fumar/legislação & jurisprudência , Inquéritos e Questionários , Impostos/economia , Produtos do Tabaco/efeitos adversos , Estados Unidos/epidemiologia
11.
Nat Commun ; 8: 14175, 2017 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-28165464

RESUMO

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.


Assuntos
Formação de Anticorpos/genética , Cromossomos Humanos/genética , Predisposição Genética para Doença , Leucemia Linfocítica Crônica de Células B/genética , Adulto , Linfócitos B/imunologia , Linfócitos B/fisiologia , Estudos de Casos e Controles , Mapeamento Cromossômico , Feminino , Estudo de Associação Genômica Ampla , Humanos , Leucemia Linfocítica Crônica de Células B/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
12.
Environ Res ; 154: 304-310, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28142053

RESUMO

Associations between long-term exposure to ambient fine particulate matter (PM2.5) and all-cause and cardiovascular mortality are well documented however less is known regarding possible interactions with cigarette smoking. We previously reported a supra-additive synergistic relationship between PM2.5 and cigarette smoking for lung cancer mortality. Here we examine interactions for all-cause and cardiovascular mortality among 429,406 current or never smoking participants in the prospective American Cancer Society Cancer Prevention Study-II with modeled PM2.5 concentrations. Cox proportional and additive hazards models were used to estimate mortality associations and interactions on the multiplicative and additive scales. A total of 146,495 all-cause and 64,339 cardiovascular (plus diabetes) deaths were observed. The hazard ratio (HR) (95% confidence interval (CI)) for cardiovascular mortality for high vs. low PM2.5 exposure (>14.44µg/m3 vs ≤10.59µg/m3, 75th vs 25th percentile) was 1.09 (95% CI 1.05, 1.12) in never smokers. The HR for cigarette smoking was 1.89 (95% CI 1.82, 1.96) in those with low PM2.5. The HR for both high PM2.5 and cigarette smoking was 2.08 (95% CI 2.00, 2.17). A small significant excess relative risk due to interaction (0.10; 95% CI 0.02, 0.19) was observed. Quantification of the public health burden attributed to the interaction between PM2.5 and cigarette smoking indicated a total of 32 (95% CI -6, 71) additional cardiovascular deaths per 100,000 person-years due to this interaction. In conclusion, PM2.5 was associated with all-cause and cardiovascular mortality in both smokers and never smokers, with some evidence for a small additive interaction with cigarette smoking. Reductions in cigarette smoking will result in the greatest impact on reducing all-cause and cardiovascular death at the levels of PM2.5 observed in this study. However, reductions in PM2.5 will also contribute to preventing a proportion of mortality attributed to cigarette smoking.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Material Particulado/efeitos adversos , Fumar/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estados Unidos/epidemiologia
13.
Cancer ; 123(11): 2014-2024, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28171707

RESUMO

BACKGROUND: Prospective cohort studies contribute importantly to understanding the role of lifestyle, genetic, and other factors in chronic disease etiology. METHODS: The American Cancer Society (ACS) recruited a new prospective cohort study, Cancer Prevention Study 3 (CPS-3), between 2006 and 2013 from 35 states and Puerto Rico. Enrollment took place primarily at ACS community events and at community enrollment "drives." At enrollment sites, participants completed a brief survey that included an informed consent, identifying information necessary for follow-up, and key exposure information. They also provided a waist measure and a nonfasting blood sample. Most participants also completed a more comprehensive baseline survey at home that included extensive medical, lifestyle, and other information. Participants will be followed for incident cancers through linkage with state cancer registries and for cause-specific mortality through linkage with the National Death Index. RESULTS: In total, 303,682 participants were enrolled. Of these, 254,650 completed the baseline survey and are considered "fully" enrolled; they will be sent repeat surveys periodically for at least the next 20 years to update exposure information. The remaining participants (n = 49,032) will not be asked to update exposure information but will be followed for outcomes. Twenty-three percent of participants were men, 17.3% reported a race or ethnicity other than "white," and the median age at enrollment was 47 years. CONCLUSIONS: CPS-3 will be a valuable resource for studies of cancer and other outcomes because of its size; its diversity with respect to age, ethnicity, and geography; and the availability of blood samples and detailed questionnaire information collected over time. Cancer 2017;123:2014-2024. © 2017 American Cancer Society.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Dieta/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Exercício , Estilo de Vida , Neoplasias/epidemiologia , Fumar/epidemiologia , Adulto , Idoso , American Cancer Society , Índice de Massa Corporal , Estudos de Coortes , Anticoncepcionais Orais Hormonais/uso terapêutico , Escolaridade , Terapia de Reposição de Estrogênios/estatística & dados numéricos , Feminino , Frutas , Humanos , Masculino , Estado Civil , Pessoa de Meia-Idade , Estudos Prospectivos , Porto Rico/epidemiologia , Carne Vermelha , Fatores de Risco , Inquéritos e Questionários , Estados Unidos/epidemiologia , Verduras , Circunferência da Cintura
14.
Environ Health Perspect ; 125(4): 552-559, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27611476

RESUMO

BACKGROUND: Remote sensing (RS) is increasingly used for exposure assessment in epidemiological and burden of disease studies, including those investigating whether chronic exposure to ambient fine particulate matter (PM2.5) is associated with mortality. OBJECTIVES: We compared relative risk estimates of mortality from diseases of the circulatory system for PM2.5 modeled from RS with that for PM2.5 modeled using ground-level information. METHODS: We geocoded the baseline residence of 668,629 American Cancer Society Cancer Prevention Study II (CPS-II) cohort participants followed from 1982 to 2004 and assigned PM2.5 levels to all participants using seven different exposure models. Most of the exposure models were averaged for the years 2002-2004, and one RS estimate was for a longer, contemporaneous period. We used Cox proportional hazards regression to estimate relative risks (RRs) for the association of PM2.5 with circulatory mortality and ischemic heart disease. RESULTS: Estimates of mortality risk differed among exposure models. The smallest relative risk was observed for the RS estimates that excluded ground-based monitors for circulatory deaths [RR = 1.02, 95% confidence interval (CI): 1.00, 1.04 per 10 µg/m3 increment in PM2.5]. The largest relative risk was observed for the land-use regression model that included traffic information (RR = 1.14, 95% CI: 1.11, 1.17 per 10 µg/m3 increment in PM2.5). CONCLUSIONS: We found significant associations between PM2.5 and mortality in every model; however, relative risks estimated from exposure models using ground-based information were generally larger than those estimated using RS alone.


Assuntos
Poluentes Atmosféricos/análise , Exposição Ambiental/estatística & dados numéricos , Material Particulado/análise , Tecnologia de Sensoriamento Remoto , Poluição do Ar/estatística & dados numéricos , Nível de Saúde , Humanos , Modelos Teóricos , Medição de Risco
15.
Air Qual Atmos Health ; 9(8): 961-972, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27867428

RESUMO

The effectiveness of regulatory actions designed to improve air quality is often assessed by predicting changes in public health resulting from their implementation. Risk of premature mortality from long-term exposure to ambient air pollution is the single most important contributor to such assessments and is estimated from observational studies generally assuming a log-linear, no-threshold association between ambient concentrations and death. There has been only limited assessment of this assumption in part because of a lack of methods to estimate the shape of the exposure-response function in very large study populations. In this paper, we propose a new class of variable coefficient risk functions capable of capturing a variety of potentially non-linear associations which are suitable for health impact assessment. We construct the class by defining transformations of concentration as the product of either a linear or log-linear function of concentration multiplied by a logistic weighting function. These risk functions can be estimated using hazard regression survival models with currently available computer software and can accommodate large population-based cohorts which are increasingly being used for this purpose. We illustrate our modeling approach with two large cohort studies of long-term concentrations of ambient air pollution and mortality: the American Cancer Society Cancer Prevention Study II (CPS II) cohort and the Canadian Census Health and Environment Cohort (CanCHEC). We then estimate the number of deaths attributable to changes in fine particulate matter concentrations over the 2000 to 2010 time period in both Canada and the USA using both linear and non-linear hazard function models.

16.
Cancer Epidemiol Biomarkers Prev ; 25(12): 1609-1618, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27587788

RESUMO

BACKGROUND: Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. METHODS: We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. RESULTS: We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10-7) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. IMPACT: A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR.


Assuntos
Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Mieloma Múltiplo/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Complexo Repressor Polycomb 1/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Repressoras/genética , Proteína Transmembrana Ativadora e Interagente do CAML/genética
17.
Environ Res ; 148: 46-54, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27015563

RESUMO

Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer. The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148Bq/m(3)) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74Bq/m(3)) radon levels (HR=1.63, 95% CI:1.23-2.18), and there was evidence of a dose-response relationship (HRcontinuous=1.38, 95% CI:1.15-1.65 per 100Bq/m(3); p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings.


Assuntos
Poluentes Radioativos do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Neoplasias Hematológicas/epidemiologia , Radônio/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Habitação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
18.
Nat Commun ; 7: 10933, 2016 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-26956414

RESUMO

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.


Assuntos
Grupo com Ancestrais do Continente Europeu/genética , Estudo de Associação Genômica Ampla , Leucemia Linfocítica Crônica de Células B/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Proteína 11 Semelhante a Bcl-2 , Predisposição Genética para Doença , Humanos , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Serpinas/genética , Proteínas com Domínio T/genética
19.
Am J Respir Crit Care Med ; 193(10): 1134-42, 2016 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-26680605

RESUMO

RATIONALE: Tropospheric ozone (O3) is potentially associated with cardiovascular disease risk and premature death. Results from long-term epidemiological studies on O3 are scarce and inconclusive. OBJECTIVES: In this study, we examined associations between chronic ambient O3 exposure and all-cause and cause-specific mortality in a large cohort of U.S. adults. METHODS: Cancer Prevention Study II participants were enrolled in 1982. A total of 669,046 participants were analyzed, among whom 237,201 deaths occurred through 2004. We obtained estimates of O3 concentrations at the participant's residence from a hierarchical Bayesian space-time model. Estimates of fine particulate matter (particulate matter with an aerodynamic diameter of up to 2.5 µm [PM2.5]) and NO2 concentrations were obtained from land use regression. Cox proportional hazards regression models were used to examine mortality associations adjusted for individual- and ecological-level covariates. MEASUREMENTS AND MAIN RESULTS: In single-pollutant models, we observed significant positive associations between O3, PM2.5, and NO2 concentrations and all-cause and cause-specific mortality. In two-pollutant models adjusted for PM2.5, significant positive associations remained between O3 and all-cause (hazard ratio [HR] per 10 ppb, 1.02; 95% confidence interval [CI], 1.01-1.04), circulatory (HR, 1.03; 95% CI, 1.01-1.05), and respiratory mortality (HR, 1.12; 95% CI, 1.08-1.16) that were unchanged with further adjustment for NO2. We also observed positive mortality associations with both PM2.5 (both near source and regional) and NO2 in multipollutant models. CONCLUSIONS: Findings derived from this large-scale prospective study suggest that long-term ambient O3 contributes to risk of respiratory and circulatory mortality. Substantial health and environmental benefits may be achieved by implementing further measures aimed at controlling O3 concentrations.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Morte , Exposição Ambiental/estatística & dados numéricos , Ozônio/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Poluição do Ar/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Porto Rico/epidemiologia , Risco , Fatores de Risco , Tempo , Estados Unidos/epidemiologia
20.
Environ Health Perspect ; 124(6): 785-94, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26629599

RESUMO

BACKGROUND: Fine particulate matter (PM2.5) air pollution exposure has been identified as a global health threat. However, the types and sources of particles most responsible are not yet known. OBJECTIVES: We sought to identify the causal characteristics and sources of air pollution underlying past associations between long-term PM2.5 exposure and ischemic heart disease (IHD) mortality, as established in the American Cancer Society's Cancer Prevention Study-II cohort. METHODS: Individual risk factor data were evaluated for 445,860 adults in 100 U.S. metropolitan areas followed from 1982 through 2004 for vital status and cause of death. Using Cox proportional hazard models, we estimated IHD mortality hazard ratios (HRs) for PM2.5, trace constituents, and pollution source-associated PM2.5, as derived from air monitoring at central stations throughout the nation during 2000-2005. RESULTS: Associations with IHD mortality varied by PM2.5 mass constituent and source. A coal combustion PM2.5 IHD HR = 1.05 (95% CI: 1.02, 1.08) per microgram/cubic meter, versus an IHD HR = 1.01 (95% CI: 1.00, 1.02) per microgram/cubic meter PM2.5 mass, indicated a risk roughly five times higher for coal combustion PM2.5 than for PM2.5 mass in general, on a per microgram/cubic meter PM2.5 basis. Diesel traffic-related elemental carbon (EC) soot was also associated with IHD mortality (HR = 1.03; 95% CI: 1.00, 1.06 per 0.26-µg/m3 EC increase). However, PM2.5 from both wind-blown soil and biomass combustion was not associated with IHD mortality. CONCLUSIONS: Long-term PM2.5 exposures from fossil fuel combustion, especially coal burning but also from diesel traffic, were associated with increases in IHD mortality in this nationwide population. Results suggest that PM2.5-mortality associations can vary greatly by source, and that the largest IHD health benefits per microgram/cubic meter from PM2.5 air pollution control may be achieved via reductions of fossil fuel combustion exposures, especially from coal-burning sources. CITATION: Thurston GD, Burnett RT, Turner MC, Shi Y, Krewski D, Lall R, Ito K, Jerrett M, Gapstur SM, Diver WR, Pope CA III. 2016. Ischemic heart disease mortality and long-term exposure to source-related components of U.S. fine particle air pollution. Environ Health Perspect 124:785-794; http://dx.doi.org/10.1289/ehp.1509777.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Isquemia Miocárdica/mortalidade , Material Particulado/análise , Adulto , Idoso , Poluentes Atmosféricos/análise , Doença da Artéria Coronariana , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Modelos de Riscos Proporcionais , Estados Unidos/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA