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1.
Int J Cancer ; 2021 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-33675538

RESUMO

Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10-7 either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33572119

RESUMO

Geocoding is a powerful tool for environmental exposure assessments that rely on spatial databases. Geocoding processes, locators, and reference datasets have improved over time; however, improvements have not been well-characterized. Enrollment addresses for the Agricultural Health Study, a cohort of pesticide applicators and their spouses in Iowa (IA) and North Carolina (NC), were geocoded in 2012-2016 and then again in 2019. We calculated distances between geocodes in the two periods. For a subset, we computed positional errors using "gold standard" rooftop coordinates (IA; N = 3566) or Global Positioning Systems (GPS) (IA and NC; N = 1258) and compared errors between periods. We used linear regression to model the change in positional error between time periods (improvement) by rural status and population density, and we used spatial relative risk functions to identify areas with significant improvement. Median improvement between time periods in IA was 41 m (interquartile range, IQR: -2 to 168) and 9 m (IQR: -80 to 133) based on rooftop coordinates and GPS, respectively. Median improvement in NC was 42 m (IQR: -1 to 109 m) based on GPS. Positional error was greater in rural and low-density areas compared to in towns and more densely populated areas. Areas of significant improvement in accuracy were identified and mapped across both states. Our findings underscore the importance of evaluating determinants and spatial distributions of errors in geocodes used in environmental epidemiology studies.

3.
Environ Health Perspect ; 129(1): 17003, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33404262

RESUMO

BACKGROUND: Farmers have a higher incidence of multiple myeloma, and there is suggestive evidence of an elevated prevalence of its precursor, monoclonal gammopathy of undetermined significance (MGUS), relative to the general population. Pesticide exposures are suspected to play a role; however, the biologic plausibility for associations with multiple myeloma remains unclear. OBJECTIVES: Our objectives were to examine the prevalence of MGUS and evaluate associations with a wide range of pesticides in a large sample of farmers. METHODS: We obtained sera and assessed MGUS among 1,638 male farmers ≥50 years of age in the Agricultural Health Study (AHS), a prospective cohort in Iowa and North Carolina. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed to estimate associations with MGUS for recent use (within the 12 months before phlebotomy) and cumulative intensity-weighted lifetime days of use of specific pesticides. RESULTS: The age-standardized MGUS prevalence was significantly elevated among AHS farmers (7.7%) compared with demographically similar men in the National Health and Nutrition Examination Survey (2.8%) or Olmsted County, Minnesota (3.8%; p<0.001). Recent use of permethrin was associated with MGUS [recent use vs. no recent use, OR=1.82 (95% CI: 1.06, 3.13)], especially among those who had also used it in the past [recent and past use vs. never use, OR=2.49 (95% CI: 1.32, 4.69)]. High intensity-weighted lifetime use of the organochlorine insecticides aldrin and dieldrin was associated with MGUS relative to those who never used either of these pesticides [OR=2.42 (95% CI: 1.29, 4.54); ptrend=0.006]. We also observed a positive association with high lifetime use of petroleum oil/distillates as an herbicide, as well as an inverse association with fonofos use. DISCUSSION: This is the largest investigation of MGUS in farmers and the first to identify an association with MGUS for permethrin, a pyrethroid insecticide previously associated with multiple myeloma. Given the continued widespread use of permethrin in various residential and commercial settings, our findings may have important implications for exposed individuals in the general population. https://doi.org/10.1289/EHP6960.

4.
Environ Int ; 146: 106187, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33126065

RESUMO

BACKGROUND: Many pesticides are known to have thyroid-disrupting properties. However, few studies have evaluated the association between specific pesticide ingredients and risk of thyroid cancer. We investigated self-reported pesticide use and incident thyroid cancer in the Agricultural Health Study (AHS), a large cohort of occupationally-exposed male pesticide applicators. METHODS: The AHS is a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. At enrollment (1993-1997) and follow-up (1999-2005), participants reported use of 50 pesticides. We characterized exposure as ever use (44 pesticides with ≥5 exposed cases) and by cumulative intensity-weighted lifetime days (22 pesticides with ≥10 exposed cases), a metric that accounts for factors that influence exposure. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression for incident thyroid (n = 85 cases) cancer among male participants using follow-up through 2014/2015. RESULTS: Use of the fungicide metalaxyl (HR = 2.03, CI:1.16-3.52) and the organochlorine insecticide lindane (HR = 1.74, CI:1.06-2.84) was associated with increased risk of thyroid cancer. The herbicide chlorimuron-ethyl was inversely associated with risk when we restricted to papillary thyroid cancer, the most common subtype (HR = 0.52, CI:0.28-0.96). High use of the insecticide carbaryl (>median intensity-weighted days) was inversely associated with thyroid cancer (HR = 0.20, CI:0.08-0.53, ptrend = 0.001). CONCLUSIONS: In this large cohort study, we observed increased risk of thyroid cancer associated with use of metalaxyl and lindane, and an inverse association with carbaryl. More work is needed to understand the potential role of these chemicals in thyroid carcinogenesis.

5.
J Natl Cancer Inst ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32944748

RESUMO

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are highly persistent chemicals that have been detected in the serum of > 98% of the U.S. population. Studies among highly exposed individuals suggest an association with perfluorooctanoic acid (PFOA) exposure and kidney cancer. It remains unclear whether PFOA or other PFAS are renal carcinogens, or if they influence risk of renal cell carcinoma (RCC) at concentrations observed in the general population. METHODS: We measured pre-diagnostic serum concentrations of PFOA and seven additional PFAS in 324 RCC cases and 324 individually matched controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs) relating serum PFAS concentrations and RCC risk. Individual PFAS were modeled continuously (log2-transformed) and categorically, with adjustment for kidney function and additional potential confounders. All statistical tests were two-sided. RESULTS: We observed a positive association with RCC risk for PFOA (doubling in serum concentration, ORcontinuous = 1.71, 95% CI = 1.23 to 2.37; P = .002), and a greater than two-fold increased risk among those in the highest quartile vs. the lowest (OR = 2.63, 95% CI = 1.33 to 5.20; Ptrend = .007). The association with PFOA was similar after adjustment for other PFAS (ORcontinuous = 1.68, 95% CI = 1.07 to 2.63; P = .02), and remained apparent in analyses restricted to individuals without evidence of diminished kidney function and in cases diagnosed ≥8 years after phlebotomy. CONCLUSIONS: Our findings add substantially to the weight of evidence that PFOA is a renal carcinogen and may have important public health implications for the many individuals exposed to this ubiquitous and highly persistent chemical.

6.
Environ Res ; 191: 110186, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919961

RESUMO

BACKGROUND: Extensive literature suggests an association between general pesticide use and Parkinson's disease (PD). However, with few exceptions, little is known about associations between specific pesticides and PD. OBJECTIVE: We evaluated use of pesticides and incident PD in 38,274 pesticide applicators and 27,836 of their spouses in the Agricultural Health Study cohort followed over 20 years. METHODS: We used self-reported information on ever-use of 50 specific pesticides as of enrollment for both applicators and spouses, and considered intensity-weighted lifetime days (IWLD) reported at enrollment and through the first 5-year follow-up among applicators. We estimated covariate-adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression. We also examined heterogeneity in associations by history of head injury and chemical resistant glove use. RESULTS: A total of 373 applicators and 118 spouses self-reported incident doctor-diagnosed PD. Ever-use of the insecticide terbufos (HR:1.31, 95%CI:1.02-1.68) and the herbicides trifluralin (HR:1.29, 95%CI: 0.99-1.70) and 2,4,5-T (HR:1.57, 95%CI:1.21-2.04) was associated with elevated PD risk. On the other hand, diazinon (HR:0.73, 95%CI: 0.58-0.94) and 2,4,5-TP (HR:0.39, 95%CI:0.25-0.62) were associated with reduced risk. We observed heterogeneity in ever-use associations by head injury and chemical-resistant glove use for some pesticides, with higher risk among those who reported a history of head injury, or who did not use gloves. PD risk was also elevated for applicators in the highest category of IWLD for dichlorvos, permethrin (animal use), and benomyl. CONCLUSIONS: We found evidence of increased PD risk for some pesticides. Our results also suggest higher susceptibility for pesticide-associated PD among individuals with head injury as well as protection with use of chemical resistant gloves, although further research is needed to understand the impact of head injury. Research on current and newer pesticides, including mechanisms relevant to PD, is important given widespread pesticide use.

7.
Cancer Epidemiol Biomarkers Prev ; 29(11): 2343-2350, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32868318

RESUMO

BACKGROUND: The etiology of myeloproliferative neoplasms (MPN) is obscure, and no previous studies have evaluated the role of diet. METHODS: In the NIH-AARP Diet and Health Study, a prospective cohort of 463,049 participants ages 50 to 71 years at baseline (1995-1996), we identified 490 MPN cases after a median follow-up of 15.5 years, including 190 with polycythemia vera (PV) and 146 with essential thrombocythemia (ET). We examined possible associations between various dietary factors and the risk of MPN as a group, as well as PV and ET, using multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) and adjust for potential confounding variables. RESULTS: An increased risk was observed between fruit consumption and the risk of MPN overall (third tertile vs. first tertile, HR = 1.32; 95% CI, 1.04-1.67; P trend = 0.02) and PV (third tertile vs. first tertile, HR = 2.00; 95% CI, 1.35-2.95; P trend < 0.01). Increased risk of PV was also observed among those with high intake of sugar (HR = 1.77; 95% CI, 1.12-2.79), sugar from natural sources (HR = 1.77; 95% CI, 1.16-2.71), sugar from natural beverage sources (HR = 1.57; 95% CI, 1.08-2.29), and fructose (HR = 1.84; 95% CI, 1.21-2.79). CONCLUSIONS: The intake of fat and protein did not appear to influence PV risk-neither did meat or vegetable consumption. None of the dietary factors studied was associated with the risk of ET. The role of sugar intake in the etiology of PV in older individuals warrants further investigation. IMPACT: Our results indicate that high sugar intake is associated with an increased risk of polycythemia vera.

8.
Environ Health Perspect ; 128(6): 67011, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32692250

RESUMO

BACKGROUND: Agricultural work and occupational pesticide use have been associated with increased risk of renal cell carcinoma (RCC), the most common form of kidney cancer. However, few prospective studies have investigated links to specific pesticides. OBJECTIVE: We evaluated the lifetime use of individual pesticides and the incidence of RCC. METHODS: We evaluated the associations between intensity-weighted lifetime days (IWDs) of 38 pesticides and incident RCC in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Among 55,873 applicators, 308 cases were diagnosed between enrollment (1993-1997) and the end of follow-up (2014-2015). We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) using Poisson regression, controlling for potential confounding factors, with lagged and unlagged pesticide exposures. RESULTS: There was a statistically significant increased risk of RCC among the highest users of 2,4,5-T compared with never users [unlagged RRIWD Tertile 3=2.92 (95% CI: 1.65, 5.17; ptrend=0.001)], with similar risk estimates for lagged exposure [20-y lag RRIWD Tertile 3=3.37 (95% CI: 1.83, 6.22; ptrend=0.001)]. In 20-y lagged analyses, we also found exposure-response associations with chlorpyrifos [RRIWD Quartile 4=1.68 (95% CI: 1.05, 2.70; ptrend=0.01)], chlordane [RRIWD Tertile 3=2.06 (95% CI: 1.10, 3.87; ptrend=0.02)], atrazine [RRIWD Quartile 4=1.43 (95% CI: 1.00, 2.03; ptrend=0.02)], cyanazine [RRIWD Quartile 4=1.61 (95% CI: 1.03, 2.50; ptrend=0.02)], and paraquat [RRIWD>Median=1.95 (95% CI: 1.03, 3.70; ptrend=0.04)]. CONCLUSIONS: This is, to our knowledge, the first prospective study to evaluate RCC risk in relation to various pesticides. We found evidence of associations with RCC for four herbicides (2,4,5-T, atrazine, cyanazine, and paraquat) and two insecticides (chlorpyrifos and chlordane). Our findings provide insights into specific chemicals that may influence RCC risk among pesticide applicators. Confirmation of these findings and investigations of the biologic plausibility and potential mechanisms underlying the observed associations are warranted. https://doi.org/10.1289/EHP6334.

9.
Blood Adv ; 4(12): 2789-2797, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32569378

RESUMO

So far, 23 germline susceptibility loci have been associated with multiple myeloma (MM) risk. It is unclear whether the genetic variation associated with MM susceptibility also predisposes to its precursor, monoclonal gammopathy of undetermined significance (MGUS). Leveraging 2434 MM cases, 754 MGUS cases, and 2 independent sets of controls (2567/879), we investigated potential shared genetic susceptibility of MM and MGUS by (1) performing MM and MGUS genome-wide association studies (GWAS); (2) validating the association of a polygenic risk score (PRS) based on 23 established MM loci (MM-PRS) with risk of MM, and for the first time with MGUS; and (3) examining genetic correlation of MM and MGUS. Heritability and genetic estimates yielded 17% (standard error [SE] ±0.04) and 15% (SE ±0.11) for MM and MGUS risk, respectively, and a 55% (SE ±0.30) genetic correlation. The MM-PRS was associated with risk of MM when assessed continuously (odds ratio [OR], 1.17 per SD; 95% confidence interval [CI], 1.13-1.21) or categorically (OR, 1.70; 95% CI, 1.38-2.09 for highest; OR, 0.71; 95% CI, 0.55-0.90 for lowest compared with middle quintile). The MM-PRS was similarly associated with MGUS (OR, 1.19 per SD; 95% CI, 1.14-1.26 as a continuous measure, OR, 1.77, 95%CI: 1.29-2.43 for highest and OR, 0.70, 95%CI: 0.50-0.98 for lowest compared with middle quintile). MM and MGUS associations did not differ by age, sex, or MM immunoglobulin isotype. We validated a 23-SNP MM-PRS in an independent series of MM cases and provide evidence for its association with MGUS. Our results suggest shared common genetic susceptibility to MM and MGUS.

10.
Int J Epidemiol ; 49(4): 1326-1337, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357211

RESUMO

BACKGROUND: The herbicide dicamba has been commonly used agriculturally and residentially. Recent approval of genetically engineered dicamba-resistant crops is expected to lead to increased dicamba use, and there has been growing interest in potential human health effects. A prior analysis in the Agricultural Health Study (AHS) suggested associations between dicamba and colon and lung cancer. We re-evaluated dicamba use in the AHS, including an additional 12 years and 2702 exposed cancers. METHODS: The AHS is a prospective cohort of pesticide applicators in Iowa and North Carolina. At enrollment (1993-1997) and follow-up (1999-2005), participants reported dicamba use. Exposure was characterized by cumulative intensity-weighted lifetime days, including exposure lags of up to 20 years. We estimated relative risks (RR) and 95% confidence intervals (CI) using multivariable Poisson regression for incident cancers diagnosed from enrollment through 2014/2015. RESULTS: Among 49 922 applicators, 26 412 (52.9%) used dicamba. Compared with applicators reporting no dicamba use, those in the highest quartile of exposure had elevated risk of liver and intrahepatic bile duct cancer (nexposed = 28, RRQ4 = 1.80, CI: 1.26-2.56, Ptrend < 0.001) and chronic lymphocytic leukaemia (CLL, nexposed = 93, RRQ4 = 1.20, CI: 0.96-1.50, Ptrend = 0.01) and decreased risk of myeloid leukaemia (nexposed = 55, RRQ4 = 0.73, CI: 0.51-1.03, Ptrend = 0.01). The associations for liver cancer and myeloid leukaemia remained after lagging exposure of up to 20 years. CONCLUSIONS: With additional follow-up and exposure information, associations with lung and colon cancer were no longer apparent. In this first evaluation of liver and intrahepatic bile duct cancer, there was an association with increasing use of dicamba that persisted across lags of up to 20 years.

11.
Br J Cancer ; 123(2): 316-324, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32376888

RESUMO

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and -ß, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated with increased ICC risk, further supporting a hormonal aetiology. However, no observational studies have examined the associations between exogenous hormone use and reproductive factors, as proxies of endogenous hormone levels, and risk of ICC. METHODS: We harmonised data from 1,107,498 women who enroled in 12 North American-based cohort studies (in the Liver Cancer Pooling Project, LCPP) and the UK Biobank between 1980-1998 and 2006-2010, respectively. Cox proportional hazards regression models were used to generate hazard ratios (HR) and 95% confidence internals (CI). Then, meta-analytic techniques were used to combine the estimates from the LCPP (n = 180 cases) and the UK Biobank (n = 57 cases). RESULTS: Hysterectomy was associated with a doubling of ICC risk (HR = 1.98, 95% CI: 1.27-3.09), compared to women aged 50-54 at natural menopause. Long-term oral contraceptive use (9+ years) was associated with a 62% increased ICC risk (HR = 1.62, 95% CI: 1.03-2.55). There was no association between ICC risk and other exogenous hormone use or reproductive factors. CONCLUSIONS: This study suggests that hysterectomy and long-term oral contraceptive use may be associated with an increased ICC risk.

12.
Int J Hyg Environ Health ; 228: 113525, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32311660

RESUMO

BACKGROUND: The observed deficit of lung cancer in farmers has been partly attributed to exposure to organic dusts and endotoxins based largely on surrogate metrics. To move beyond these surrogates for etiological studies, we characterized task-based and time-weighted average (TWA) exposure to inhalable endotoxin, (1 â†’ 3)-ß-D-glucan, and dust in Iowa farmers. METHODS: We collected 320 personal inhalable dust samples from 32 farmers during 69 sample days in 2015 and 2016. Samples were collected using Button aerosol samplers and analyzed for endotoxin using a kinetic chromogenic amebocyte lysate assay, and for (1 â†’ 3)-ß-D-glucan using a Limulus endpoint assay. We assessed relationships between bioaerosol concentrations and selected tasks and farm characteristics using linear mixed-effects models. RESULTS: Bedding work, hog handling, and working in barn/confinement buildings, grain bins, and grain elevators were associated with higher endotoxin exposure. We found a monotonic trend between higher endotoxin concentrations and increasing number of animals. Bedding work, cleaning, and feed/grain storage work were associated with higher (1 â†’ 3)-ß-D-glucan concentrations. The median concentrations by task spanned one order of magnitude for inhalable dust and two orders of magnitude for endotoxin and (1 â†’ 3)-ß-D-glucan. Pearson correlations between endotoxin and glucan concentrations were 0.22 for TWA exposure and 0.56 for task samples. CONCLUSIONS: This characterization of exposure factors that influence bioaerosol concentrations can support the development of refined bioaerosol exposure metrics for future etiologic analyses of cancer and other health outcomes in farmers.

13.
Environ Health ; 19(1): 30, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138787

RESUMO

BACKGROUND: Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men in developed countries; however, little is known about modifiable risk factors. Some studies have implicated organochlorine and organophosphate insecticides as risk factors (particularly the organodithioate class) and risk of clinically significant PCa subtypes. However, few studies have evaluated other pesticides. We used data from the Agricultural Health Study, a large prospective cohort of pesticide applicators in North Carolina and Iowa, to extend our previous work and evaluate 39 additional pesticides and aggressive PCa. METHODS: We used Cox proportional hazards models, with age as the time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ever use of individual pesticides and 883 cases of aggressive PCa (distant stage, poorly differentiated grade, Gleason score ≥ 7, or fatal prostate cancer) diagnosed between 1993 and 2015. All models adjusted for birth year, state, family history of PCa, race, and smoking status. We conducted exposure-response analyses for pesticides with reported lifetime years of use. RESULTS: There was an increased aggressive PCa risk among ever users of the organodithioate insecticide dimethoate (n = 54 exposed cases, HR = 1.37, 95% CI = 1.04, 1.80) compared to never users. We observed an inverse association between aggressive PCa and the herbicide triclopyr (n = 35 exposed cases, HR = 0.68, 95% CI = 0.48, 0.95), with the strongest inverse association for those reporting durations of use above the median (≥ 4 years; n = 13 exposed cases, HR=0.44, 95% CI=0.26, 0.77). CONCLUSION: Few additional pesticides were associated with prostate cancer risk after evaluation of extended data from this large cohort of private pesticide applicators.


Assuntos
Doenças dos Trabalhadores Agrícolas/epidemiologia , Praguicidas/efeitos adversos , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Humanos , Incidência , Iowa/epidemiologia , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Prevalência , Estudos Prospectivos , Neoplasias da Próstata/induzido quimicamente , Fatores de Risco , Adulto Jovem
15.
Epidemiology ; 31(4): 478-489, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32168021

RESUMO

BACKGROUND: Although occupational exposure to animals has been associated with lymphohematopoietic malignancies, to our knowledge no studies have evaluated adult cancer risks associated with living near intensive animal agriculture. METHODS: We linked participants in the prospective Agricultural Health Study to permitted animal feeding operations in Iowa. We created metrics reflecting the intensity of animal exposures within 2 and 5 km of participants' residences, enumerating both total and inverse distance-weighted animal units (AUs), standardized by animal size and manure production. We estimated risk of lymphohematopoietic malignancies and subtypes [hazard ratio (HR), 95% confidence interval (95% CI)], adjusting for demographic and farming-related factors, including occupational pesticide exposure. We stratified associations by animal type and animal-related work activities. RESULTS: We observed 519 cases (1993-2015) among 32,635 pesticide applicators and 211 cases among 19,743 spouses. Among applicators, no associations were evident within 2 km, but risk of any lymphohematopoietic cancer was elevated across quintiles of weighted AUs within 5 km. Risk of non-Hodgkin lymphoma (NHL) was elevated for the second (HR = 1.5; 95% CI, 1.1, 2.1), third (HR = 1.6; 95% CI, 1.1, 2.2), and fourth (HR = 1.7; 95% CI, 1.3, 2.4) highest quintiles of weighted AUs within 5 km (Ptrend = 0.52) and increased with dairy cattle AUs (Ptrend = 0.04). We found positive trends for leukemia and some NHL subtypes with increasing numbers of both beef and dairy cattle. Risks did not vary by animal-related work (Pinteraction = 0.61). Associations were similar using the total exposure metric and inconsistent among spouses. CONCLUSION: Residential proximity to intensive animal agriculture was positively associated with risk of NHL and leukemia, even after consideration of occupational animal and pesticide exposures.

16.
Ann Work Expo Health ; 64(5): 503-513, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32219300

RESUMO

OBJECTIVES: Daily driving of diesel-powered tractors has been linked to increased lung cancer risk in farmers, yet few studies have quantified exposure levels to diesel exhaust during tractor driving or during other farm activities. We expanded an earlier task-based descriptive investigation of factors associated with real-time exposure levels to black carbon (BC, a surrogate of diesel exhaust) in Iowa farmers by increasing the sample size, collecting repeated measurements, and applying statistical models adapted to continuous measurements. METHODS: The expanded study added 43 days of sampling, for a total of 63 sample days conducted in 2015 and 2016 on 31 Iowa farmers. Real-time, continuous monitoring (30-s intervals) of personal BC concentrations was performed using a MicroAeth AE51 microaethelometer affixed with a micro-cyclone. A field researcher recorded information on tasks, fuel type, farmer location, and proximity to burning biomass. We evaluated the influence of these variables on log-transformed BC concentrations using a linear mixed-effect model with random effects for farmer and day and a first-order autoregressive structure for within-day correlation. RESULTS: Proximity to diesel-powered equipment was observed for 42.5% of the overall sampling time and on 61 of the 63 sample days. Predicted geometric mean BC concentrations were highest during grain bin work, loading, and harvesting, and lower for soil preparation and planting. A 68% increase in BC concentrations was predicted for close proximity to a diesel-powered vehicle, relative to far proximity, while BC concentrations were 44% higher in diesel vehicles with open cabins compared with closed cabins. Task, farmer location, fuel type, and proximity to burning biomass explained 8% of within-day variance in BC concentrations, 2% of between-day variance, and no between-farmer variance. CONCLUSION: Our findings showed that farmers worked frequently near diesel equipment and that BC concentrations varied between tasks and by fuel type, farmer location, and proximity to burning biomass. These results could support the development of exposure models applicable to investigations of health effects in farmers associated with exposure to diesel engine exhaust.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32069802

RESUMO

Timing of breast development (or thelarche) and its endogenous and exogenous determinants may underlie global variation in breast cancer incidence. The study objectives were to characterize endogenous estrogen levels and bisphenol A (BPA) exposure using a migrant study of adolescent girls and test whether concentrations explained differences in thelarche by birthplace and growth environment. Estrogen metabolites (EM) and BPA-glucuronide (BPA-G) were quantified in urine spot samples using liquid chromatography tandem mass spectrometry (LC-MS/MS) from a cross-sectional study of Bangladeshi, first- and second-generation Bangladeshi migrants to the UK, and white British girls aged 5-16 years (n = 348). Thelarche status at the time of interview was self-reported and defined equivalent to Tanner Stage ≥2. We compared geometric means (and 95% confidence interval (CIs)) of EM and BPA-G using linear regression and assessed whether EM and BPA-G explained any of the association between exposure to the UK and the age at thelarche using hazard ratios and 95% confidence intervals. Average EM decreased with exposure to the UK, whereas BPA-G increased and was significantly higher among white British (0.007 ng/mL, 95% CI: 0.0024-0.0217) and second-generation British-Bangladeshi girls (0.009 ng/mL, 95% CI: 0.0040-0.0187) compared to Bangladeshi girls (0.002 ng/mL, 95% CI: 0.0018-0.0034). Two of four EM ratios (16-pathway/parent and parent/all pathways) were significantly associated with thelarche. The relationship between exposure to the UK and thelarche did not change appreciably after adding EM and BPA-G to the models. While BPA-G is often considered a ubiquitous exposure, our findings suggest it can vary based on birthplace and growth environment, with increasing levels for girls who were born in or moved to the UK. Our study did not provide statistically significant evidence that BPA-G or EM concentrations explained earlier thelarche among girls who were born or raised in the UK.


Assuntos
Compostos Benzidrílicos , Mama , Estrogênios , Fenóis , Espectrometria de Massas em Tandem , Adolescente , Bangladesh , Compostos Benzidrílicos/toxicidade , Mama/crescimento & desenvolvimento , Criança , Pré-Escolar , Cromatografia Líquida , Estudos Transversais , Estrogênios/metabolismo , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Menarca , Fenóis/toxicidade , Reino Unido
18.
Int J Cancer ; 147(4): 948-957, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31904114

RESUMO

The etiology of Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) is largely unknown. We assessed potential associations between lifestyle factors and MPN risk in the NIH-AARP Diet and Health Study. In this prospective cohort with 463,049 participants aged 50-71 years at baseline (1995-1996) and a median follow-up of 15.5 years, we identified 490 MPN cases, including 190 with polycythemia vera (PV) and 146 with essential thrombocythemia (ET). Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Smoking was not associated with MPN risk in the overall cohort, but analyses stratified by sex suggested that smoking increased the risk of MPN in women (former smoker vs. nonsmokers, HR = 1.43, 95% CI: 1.03-2.00, p = 0.03; current smokers vs. nonsmokers, HR = 1.71, 95% CI: 1.08-2.71, p = 0.02). Coffee consumption was inversely associated with the risk of PV (high vs. low intake, HR = 0.53, 95% CI: 0.33-0.84, p-trend < 0.01), but not the risk of ET or MPN overall. Further analysis revealed an inverse association between the amount of caffeine intake and PV risk (high vs. low intake, HR = 0.55, 95% CI: 0.39-0.79, p-trend < 0.01). While the consumption of caffeinated coffee appeared to confer a protective effect against PV, the consumption of decaffeinated coffee did not. This large prospective study identified smoking as a risk factor for MPN in women and suggests that caffeine intake is associated with a lower risk of PV.

19.
Hepatology ; 72(2): 535-547, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31808181

RESUMO

BACKGROUND AND AIMS: In almost all countries, incidence rates of liver cancer (LC) are 100%-200% higher in males than in females. However, this difference is predominantly driven by hepatocellular carcinoma (HCC), which accounts for 75% of LC cases. Intrahepatic cholangiocarcinoma (ICC) accounts for 12% of cases and has rates only 30% higher in males. Hormones are hypothesized to underlie observed sex differences. We investigated whether prediagnostic circulating hormone and sex hormone binding globulin (SHBG) levels were associated with LC risk, overall and by histology, by leveraging resources from five prospective cohorts. APPROACH AND RESULTS: Seven sex steroid hormones and SHBG were quantitated using gas chromatography/tandem mass spectrometry and competitive electrochemiluminescence immunoassay, respectively, from baseline serum/plasma samples of 191 postmenopausal female LC cases (HCC, n = 83; ICC, n = 56) and 426 controls, matched on sex, cohort, age, race/ethnicity, and blood collection date. Odds ratios (ORs) and 95% confidence intervals (CIs) for associations between a one-unit increase in log2 hormone value (approximate doubling of circulating concentration) and LC were calculated using multivariable-adjusted conditional logistic regression. A doubling in the concentration of 4-androstenedione (4-dione) was associated with a 50% decreased LC risk (OR = 0.50; 95% CI = 0.30-0.82), whereas SHBG was associated with a 31% increased risk (OR = 1.31; 95% CI = 1.05-1.63). Examining histology, a doubling of estradiol was associated with a 40% increased risk of ICC (OR = 1.40; 95% CI = 1.05-1.89), but not HCC (OR = 1.12; 95% CI = 0.81-1.54). CONCLUSIONS: This study provides evidence that higher levels of 4-dione may be associated with lower, and SHBG with higher, LC risk in women. However, this study does not support the hypothesis that higher estrogen levels decrease LC risk. Indeed, estradiol may be associated with an increased ICC risk.

20.
Cancer Causes Control ; 31(1): 85-93, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31782041

RESUMO

PURPOSE: Renal cell carcinoma (RCC) incidence is higher among black than white Americans. The reasons for this disparity remain unclear. METHODS: We calculated race- and sex-specific population attributable risk percentages (PAR%) and their 95% confidence intervals (CI) for hypertension and chronic kidney disease (CKD) among black and white subjects ≥ 50 years of age from the US Kidney Cancer Study (USKC; 965 cases, 953 controls), a case-control study in Chicago and Detroit, and a nested case-control study in the Kaiser Permanente Northern California health care network (KPNC; 2,162 cases, 21,484 controls). We also estimated PAR% for other modifiable RCC risk factors (cigarette smoking, obesity) in USKC. RESULTS: In USKC, the PAR% for hypertension was 50% (95% CI 24-77%) and 44% (95% CI 25-64%) among black women and men, respectively, and 29% (95% CI 13-44%) and 27% (95% CI 14-39%) for white women and men, respectively. In KPNC, the hypertension PAR% was 40% (95% CI 18-62%) and 23% (95% CI 2-44%) among black women and men, and 27% (95% CI 20-35%) and 19% (95% CI 14-24%) among white women and men, respectively. The PAR% for CKD in both studies ranged from 7 to 10% for black women and men but was negligible (<1%) for white subjects. In USKC, the PAR% for current smoking was 20% and 8% among black and white men, respectively, and negligible and 8.6% for black and white women, respectively. The obesity PAR% ranged from 12 to 24% across all race/sex strata. CONCLUSIONS: If the associations found are causal, interventions that prevent hypertension and CKD among black Americans could potentially eliminate the racial disparity in RCC incidence (hypothetical black:white RCC incidence ratio of 0.5).


Assuntos
Carcinoma de Células Renais/epidemiologia , Disparidades nos Níveis de Saúde , Neoplasias Renais/epidemiologia , Adulto , Afro-Americanos , Idoso , California/epidemiologia , Carcinoma de Células Renais/complicações , Carcinoma de Células Renais/etnologia , Estudos de Casos e Controles , Chicago/epidemiologia , Comorbidade , Registros Eletrônicos de Saúde , Grupo com Ancestrais do Continente Europeu , Feminino , Disparidades em Assistência à Saúde , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertensão/etnologia , Incidência , Neoplasias Renais/complicações , Neoplasias Renais/etnologia , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Obesidade , Prevalência , Fatores de Risco , Fumar , Adulto Jovem
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