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1.
Clin Cancer Res ; 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849962

RESUMO

PURPOSE: Exome and whole-genome sequencing of muscle-invasive bladder cancer (BC) has revealed important insights into the molecular landscape; however, there are few studies of non-muscle invasive BC with detailed risk factor information. EXPERIMENTAL DESIGN: We examined the relationship between smoking and other BC risk factors and somatic mutations and mutational signatures in bladder tumors. Targeted sequencing of frequently mutated genes in BC was conducted in 322 formalin-fixed paraffin-embedded bladder tumors from a population-based case-control study. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), evaluating mutations and risk factors. We used SignatureEstimation to extract four known single base substitution mutational signatures and Poisson regression to calculate risk ratios (RRs) and 95%CIs, evaluating signatures and risk factors. Results:Non-silent KDM6A mutations were more common in females than males (OR=1.83,95%CI:1.05-3.19). There was striking heterogeneity in the relationship between smoking status and established single base substitution signatures: current smoking status was associated with greater ERCC2-Signature mutations compared to former (p-value=0.024) and never smoking (RR=1.40, 95% CI: 1.09-1.80, p-value=0.008); former smoking was associated with greater APOBEC-Signature13 mutations (p-value=0.05); and never smoking was associated with greater APOBEC-Signature2 mutations (RR=1.54, 95% CI: 1.17-2.01, p-value=0.002). There was evidence that smoking duration (the component most strongly associated with BC risk) was associated with ERCC2-Signature mutations and APOBEC-Signature13 mutations among current (p-trend=0.005) and former smokers (p=0.0004), respectively. CONCLUSIONS: These data quantify the contribution of BC risk factors to mutational burden and suggest different signature enrichments among never, former, and current smokers.

2.
Nat Commun ; 12(1): 1236, 2021 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-33623038

RESUMO

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p < 10-180). Comparing the 80th/20th PHS2 percentiles, hazard ratios for prostate cancer, aggressive cancer, and prostate-cancer-specific death are 5.32, 5.88, and 5.68, respectively. Within European, Asian, and African ancestries, hazard ratios for prostate cancer are: 5.54, 4.49, and 2.54, respectively. PHS2 risk-stratifies men for any, aggressive, and fatal prostate cancer in a multi-ethnic dataset.


Assuntos
Grupos Étnicos/genética , Herança Multifatorial/genética , Neoplasias da Próstata/genética , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Autorrelato
3.
Int J Cancer ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33506540

RESUMO

Twin studies suggest a familial aggregation of bladder cancer, but elements of this increased familial risk of bladder cancer are not well understood. To characterize familial risk of bladder cancer, we examined the relationship between family history of bladder and other types of cancer among first-degree relatives and risk of bladder cancer in 1193 bladder cancer cases and 1418 controls in a large population-based case-control study. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between family history of bladder cancer (defined as at least one first-degree family member with bladder cancer or a cancer of any other site). We also evaluated cancer aggregation of specific sites in family members. Participants with a first-degree relative with bladder cancer had nearly double the risk of bladder cancer (OR = 1.8, 95% CI 1.2-2.9) as those without a family history of bladder cancer. Risk was increased for having a sibling with bladder cancer (OR = 2.6, 95% CI 1.3-5.3) compared to no siblings with cancer. Bladder cancer risk was elevated when participants reported a first-degree relative with a history of female genital cancer (OR = 1.5, 95% CI 1.1-2.1), melanoma (OR = 1.9, 95% CI 1.02-3.6), and tobacco-associated cancer (OR = 1.3, 95% CI 1.06-1.6). These findings add to evidence of a familial predisposition to bladder cancer. Clarification of the aggregation of bladder cancer in families and with other cancer sites will be of interest as many loci and common polymorphisms related to bladder cancer have yet to be identified in large genomic studies.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33420416

RESUMO

BACKGROUND: Polygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46). MATERIALS AND METHOD: 180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy. RESULTS: 166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer. CONCLUSIONS: Incorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

5.
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.

6.
Cancers (Basel) ; 12(11)2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33158149

RESUMO

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.

7.
Occup Environ Med ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097675

RESUMO

OBJECTIVES: Pesticide exposure may impair human olfaction, but empirical evidence is limited. We examined associations between occupational use of 50 specific pesticides and olfactory impairment, both self-reported, among 20 409 participants in the Agricultural Health Study, a prospective cohort of pesticide applicators (mostly farmers, 97% male). METHODS: We used logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between pesticide use at enrolment (1993-1997) and olfactory impairment reported two decades later (2013-2016), adjusting for baseline covariates. RESULTS: About 10% of participants reported olfactory impairment. The overall cumulative days of any pesticide use at enrolment were associated with a higher odds of reporting olfactory impairment (OR (highest vs lowest quartile): 1.17 (95% CI: 1.02 to 1.34), p-trend = 0.003). In the analyses of 50 specific pesticides, ever-use of 20 pesticides showed modest associations with olfactory impairment, with ORs ranging from 1.11 to 1.33. Of these, higher lifetime days of use of 12 pesticides were associated with higher odds of olfactory impairment compared with never use (p-trend ≤ 0.05), including two organochlorine insecticides (dichlorodiphenyltrichloroethane and lindane), two organophosphate insecticides (diazinon and malathion), permethrin, the fungicide captan and six herbicides (glyphosate, petroleum distillates, 2,4-dichlorophenoxyacetic acid, 2,4,5-trichlorophenoxyacetic acid and metribuzin), although many of these did not exhibit clear, monotonic exposure-response patterns. CONCLUSION: Overall, we found relatively broad associations between pesticides and olfactory impairment, involving many individual pesticides and covering several chemical classes, suggesting that pesticides could affect olfaction through multiple pathways. Future epidemiological studies with objective measurement of olfaction are required to confirm these findings.

8.
J Natl Cancer Inst ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010161

RESUMO

BACKGROUND: In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. METHODS: Among prostate cancer cases diagnosed in 2007 in the U.S. SEER-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). RESULTS: In our case population (n = 55,900), 3,073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM stage and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of stage T4 or N1 or M1 or Gleason score ≥8 prostate cancer, as this definition had one of the higher PPVs (0.23, 95% confidence interval [CI] 0.22-0.24) and reasonable sensitivity (0.66, 95% CI 0.64-0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. CONCLUSIONS: We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced stage (T4 or N1 or M1), high grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.

9.
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.

10.
Environ Epidemiol ; 4(3): e097, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32613154

RESUMO

Evidence from epidemiologic and laboratory studies relating pesticides to breast cancer risk is inconsistent. Women engaging in agricultural work or living in agricultural areas may experience appreciable exposures to a wide range of pesticides, including herbicides, fumigants, and fungicides. Methods: We examined exposure to herbicides, fumigants, and fungicides in relation to breast cancer risk among farmers' wives with no prior history of breast cancer in the Agricultural Health Study. Women provided information on pesticide use, demographics, and reproductive history at enrollment (1993-1997) and at a 5-year follow-up interview. We used Cox proportional hazards regression to estimate associations (hazard ratios [HRs] and 95% confidence intervals [CIs]) between the women's and their husbands' self-reported use of individual pesticides and incident breast cancer risk. Results: Out of 30,594 women, 38% reported using herbicides, fumigants, or fungicides and 1,081 were diagnosed with breast cancer during a median 15.3 years of follow-up. We found elevated risk in relation to women's ever use of the fungicide benomyl (HR = 1.6; 95% CI = 0.9, 2.7) and the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) (HR = 1.6; 95% CI = 0.8, 3.1) and to their husbands' use of the herbicide 2-(2,4,5-trichlorophenoxy) propionic acid (2,4,5-TP) (HR = 1.5; 95% CI = 0.9, 2.7). We observed few other chemical associations and little evidence of differential risk by tumor estrogen receptor status or linear exposure-response relationships. Conclusion: We did not observe clear excesses between use of specific pesticides and breast cancer risk across exposure metrics, although we did observe elevated risk associated with women's use of benomyl and 2,4,5-T and husbands' use of 2,4,5-TP.

11.
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.

12.
Int J Cancer ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32574374

RESUMO

Insecticide use has been linked to increased risk of non-Hodgkin lymphoma (NHL), however, findings of epidemiologic studies have been inconsistent, particularly for NHL subtypes. We analyzed 1690 NHL cases and 5131 controls in the North American Pooled Project (NAPP) to investigate self-reported insecticide use and risk of NHL overall and by subtypes: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and small lymphocytic lymphoma (SLL). Odds ratios (OR) and 95% confidence intervals for each insecticide were estimated using logistic regression. Subtype-specific associations were evaluated using ASSET (Association analysis for SubSETs). Increased risks of multiple NHL subtypes were observed for lindane (OR = 1.60, 1.20-2.10: FL, DLCBL, SLL), chlordane (OR = 1.59, 1.17-2.16: FL, SLL) and DDT (OR = 1.36, 1.06-1.73: DLBCL, SLL). Positive trends were observed, within the subsets with identified associations, for increasing categories of exposure duration for lindane (Ptrend = 1.7 × 10-4 ), chlordane (Ptrend = 1.0 × 10-3 ) and DDT (Ptrend = 4.2 × 10-3 ), however, the exposure-response relationship was nonlinear. Ever use of pyrethrum was associated with an increased risk of FL (OR = 3.65, 1.45-9.15), and the relationship with duration of use appeared monotonic (OR for >10 years: OR = 5.38, 1.75-16.53; Ptrend = 3.6 × 10-3 ). Our analysis identified several novel associations between insecticide use and specific NHL subtypes, suggesting possible etiologic heterogeneity in the context of pesticide exposure.

13.
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.

14.
Cancer Causes Control ; 31(6): 583-599, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32314107

RESUMO

PURPOSE: The purpose of this study was to investigate associations between pesticide exposures and risk of Hodgkin lymphoma (HL) using data from the North American Pooled Project (NAPP). METHODS: Three population-based studies conducted in Kansas, Nebraska, and six Canadian provinces (HL = 507, Controls = 3886) were pooled to estimate odds ratios and 95% confidence intervals for single (never/ever) and multiple (0, 1, 2-4, ≥ 5) pesticides used, duration (years) and, for select pesticides, frequency (days/year) using adjusted logistic regression models. An age-stratified analysis (≤ 40/ > 40 years) was conducted when numbers were sufficient. RESULTS: In an analysis of 26 individual pesticides, ever use of terbufos was significantly associated with HL (OR: 2.53, 95% CI 1.04-6.17). In age-stratified analyses, associations were stronger among those ≤ 40 years of age. No significant associations were noted among those > 40 years old; however, HL cases ≤ 40 were three times more likely to report ever using dimethoate (OR: 3.76 95% CI 1.02-33.84) and almost twice as likely to have ever used malathion (OR: 1.86 95% CI 1.00-3.47). Those ≤ 40 years of age reporting use of 5 + organophosphate insecticides had triple the odds of HL (OR: 3.00 95% CI 1.28-7.03). Longer duration of use of 2,4-D, ≥ 6 vs. 0 years, was associated with elevated odds of HL (OR: 2.59 95% CI 1.34-4.97). CONCLUSION: In the NAPP, insecticide use may increase the risk of HL, but results are based on small numbers.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Doença de Hodgkin/epidemiologia , Praguicidas , Adulto , Canadá/epidemiologia , Humanos , Kansas/epidemiologia , Nebraska/epidemiologia
15.
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
16.
Environ Int ; 135: 105346, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31864026

RESUMO

BACKGROUND: The International Agency for Research on Cancer (IARC) classifies diesel engine exhaust as carcinogenic to humans based on sufficient evidence for lung cancer. IARC noted, however, an increased risk of bladder cancer (based on limited evidence). OBJECTIVE: To evaluate the association between quantitative, lifetime occupational diesel exhaust exposure and risk of urothelial cell carcinoma of the bladder (UBC) overall and according to pathological subtypes. METHODS: Data from personal interviews with 1944 UBC cases, as well as formalin-fixed paraffin-embedded tumor tissue blocks, and 2135 controls were pooled from two case-control studies conducted in the U.S. and Spain. Lifetime occupational histories combined with exposure-oriented questions were used to estimate cumulative exposure to respirable elemental carbon (REC), a primary surrogate for diesel exhaust. Unconditional logistic regression and two-stage polytomous logistic regression were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for smoking and other risk factors. RESULTS: Exposure to cumulative REC was associated with an increased risk of UBC; workers with cumulative REC >396 µg/m3-years had an OR of 1.61 (95% CI, 1.08-2.40). At this level of cumulative exposure, similar results were observed in the U.S. and Spain, OR = 1.75 (95% CI, 0.97-3.15) and OR = 1.54 (95% CI, 0.89-2.68), respectively. In lagged analysis, we also observed a consistent increased risk among workers with cumulative REC >396 µg/m3-years (range of ORs = 1.52-1.93) for all lag intervals evaluated (5-40 years). When we accounted for tumor subtypes defined by stage and grade, a significant association between diesel exhaust exposure and UBC was apparent (global test for association p = 0.0019). CONCLUSIONS: Combining data from two large epidemiologic studies, our results provide further evidence that diesel exhaust exposure increases the risk of UBC.


Assuntos
Poluentes Ocupacionais do Ar , Exposição Ocupacional , Neoplasias da Bexiga Urinária , Emissões de Veículos , Poluentes Ocupacionais do Ar/toxicidade , Humanos , Fatores de Risco , Espanha , Neoplasias da Bexiga Urinária/epidemiologia , Emissões de Veículos/toxicidade
18.
Epidemiology ; 31(1): 136-144, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31577632

RESUMO

BACKGROUND: N-nitroso compounds are hypothesized human bladder carcinogens. We investigated ingestion of N-nitroso compound precursors nitrate and nitrite from drinking water and diet and bladder cancer in the New England Bladder Cancer Study. METHODS: Using historical nitrate measurements for public water supplies and measured and modeled values for private wells, as well as self-reported water intake, we estimated average nitrate concentrations (mg/L NO3-N) and average daily nitrate intake (mg/d) from 1970 to diagnosis/reference date (987 cases and 1,180 controls). We estimated overall and source-specific dietary nitrate and nitrite intakes using a food frequency questionnaire (1,037 cases and 1,225 controls). We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI). We evaluated interactions with factors that may affect N-nitroso compound formation (i.e., red meat, vitamin C, smoking), and with water intake. RESULTS: Average drinking water nitrate concentration above the 95th percentile (>2.07 mg/L) compared with the lowest quartile (≤0.21 mg/L) was associated with bladder cancer (OR = 1.5, 95% CI = 0.97, 2.3; P trend = 0.01); the association was similar for average daily drinking water nitrate intake. We observed positive associations for dietary nitrate and nitrite intakes from processed meat (highest versus lowest quintile OR for nitrate = 1.4, 95% CI = 1.0, 2.0; P trend = 0.04; OR for nitrite = 1.5, 95% CI = 1.0, 2.1; P trend = 0.04, respectively), but not other dietary sources. We observed positive interactions between drinking water nitrate and red meat (P-interaction 0.05) and processed red meat (0.07). CONCLUSIONS: Our results suggest the importance of both drinking water and dietary nitrate sources as risk factors for bladder cancer.

19.
Occup Environ Med ; 76(9): 632-643, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31413186

RESUMO

OBJECTIVES: Lower mortality rates compared with the general population have been reported for Agricultural Health Study (AHS) participants (enrolled 1993-1997) followed through 2007. We extended analysis of mortality among AHS participants (51 502 private pesticide applicators, their 31 867 spouses and 4677 commercial pesticide applicators from North Carolina and Iowa) through 2015 and compared results using several analytical approaches. METHODS: We calculated standardised mortality ratios (SMRs), causal mortality ratios (CMR) and relative SMRs (rSMR) using state-specific mortality rates of the general populations as the referent. RESULTS: Over the average 16 years of follow-up (1999-2015), 9305 private applicators, 3384 spouses and 415 commercial applicators died. SMRs and CMRs, with expected deaths calculated using the person-time among the cohort and the general population, respectively, indicated lower overall mortality in all study subgroups (SMRs from 0.61 to 0.69 and CMRs from 0.74 to 0.89), although CMRs indicated elevated mortality in private applicators from North Carolina and in ever-smokers. In SMR analyses, there were fewer than expected deaths from many causes, but deaths from some external causes including transportation-related injuries and mechanical forces were elevated in private applicators. CMRs indicated higher than expected deaths from prostate cancer, lymphohaematopoietic cancers, Parkinson's and Alzheimer's disease, and chronic glomerulonephritis in private applicators, and non-Hodgkin's lymphoma in spouses (from 1.19 to 1.53). rSMR results were generally elevated, similar to CMR findings. CONCLUSIONS: AHS participants experienced lower overall mortality than the general population.Mortality from a few specific causes was increased in private applicators, specifically when CMR and rSMR approaches were used.


Assuntos
Doenças dos Trabalhadores Agrícolas/mortalidade , Mortalidade , Exposição Ocupacional/efeitos adversos , Saúde do Trabalhador , Praguicidas/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fazendeiros , Feminino , Humanos , Iowa/epidemiologia , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Cônjuges , Inquéritos e Questionários , Taxa de Sobrevida/tendências , Adulto Jovem
20.
Occup Environ Med ; 76(9): 680-687, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31308155

RESUMO

OBJECTIVES: The validity of surrogate measures of retrospective occupational exposure in population-based epidemiological studies has rarely been evaluated. Using toenail samples as bioindicators of exposure, we assessed whether work tasks and expert assessments of occupational metal exposure obtained from personal interviews were associated with lead and manganese concentrations. METHODS: We selected 609 controls from a case-control study of bladder cancer in New England who had held a job for ≥1 year 8-24 months prior to toenail collection. We evaluated associations between toenail metal concentrations and five tasks extracted from occupational questionnaires (grinding, painting, soldering, welding, working near engines) using linear regression models. For 139 subjects, we also evaluated associations between the toenail concentrations and exposure estimates from three experts. RESULTS: We observed a 1.9-fold increase (95% CI 1.4 to 2.5) in toenail lead concentrations with painting and 1.4-fold increase (95% CI 1.1 to 1.7) in manganese concentrations with working around engines and handling fuel. We observed significant trends with increasing frequency of both activities. For lead, significant trends were observed with the ratings from all three experts. Their average ratings showed the strongest association, with subjects rated as possibly or probably exposed to lead having concentrations that were 2.0 and 2.5 times higher, respectively, than in unexposed subjects (ptrend <0.001). Expert estimates were only weakly associated with manganese toenail concentrations. CONCLUSIONS: Our findings support the ability of experts to identify broad contrasts in previous occupational exposure to lead. The stronger associations with task frequency and expert assessments support using refined exposure characterisation whenever possible.


Assuntos
Chumbo/análise , Manganês/análise , Exposição Ocupacional/análise , Adulto , Idoso , Monitoramento Biológico/métodos , Estudos de Casos e Controles , Feminino , Humanos , Maine , Masculino , Pessoa de Meia-Idade , Unhas/química , New Hampshire , Estudos Retrospectivos , Vermont
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