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1.
Cancer Causes Control ; 30(9): 967-978, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31236792

RESUMO

PURPOSE: Although the incidence rate of epithelial ovarian cancer (EOC) is somewhat lower in African American (AA) than white women, survival is worse. The Ovarian Cancer in Women of African Ancestry (OCWAA) consortium will overcome small, study-specific sample sizes to better understand racial differences in EOC risk and outcomes. METHODS: We harmonized risk factors and prognostic characteristics from eight U.S. STUDIES: the North Carolina Ovarian Cancer Study (NCOCS), the Los Angeles County Ovarian Cancer Study (LACOCS), the African American Cancer Epidemiology Study (AACES), the Cook County Case-Control Study (CCCCS), the Black Women's Health Study (BWHS), the Women's Health Initiative (WHI), the Multiethnic Cohort Study (MEC), and the Southern Community Cohort Study (SCCS). RESULTS: Determinants of disparities for risk and survival in 1,146 AA EOC cases and 2,922 AA controls will be compared to 3,368 white EOC cases and 10,270 white controls. Analyses include estimation of population-attributable risk percent (PAR%) by race. CONCLUSION: OCWAA is uniquely positioned to study the epidemiology of EOC in AA women compared with white women to address disparities. Studies of EOC have been underpowered to address factors that may explain AA-white differences in the incidence and survival. OCWAA promises to provide novel insight into disparities in ovarian cancer.


Assuntos
Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/epidemiologia , Adulto , Negro ou Afro-Americano , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Illinois/epidemiologia , Incidência , Pessoa de Meia-Idade , North Carolina/epidemiologia , Fatores de Risco , Estados Unidos , População Branca , Adulto Jovem
2.
Cancer Causes Control ; 28(4): 289-297, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28224412

RESUMO

PURPOSE: Use of antihypertensive medications has been associated with renal cell carcinoma (RCC), but it is unclear whether specific types of medications increase RCC risk independent of the effect of hypertension, or whether the association varies by histologic subtype. To address this question, we analyzed data from a U.S. population-based case-control study of RCC. METHODS: We collected information on participants' use of drugs to treat hypertension, heart problems, weight control, and swelling. We computed odds ratios (ORs) and 95% confidence intervals (CIs) for each of four major drug classes, separately for participants with (643 cases, 443 controls) and without (500 cases, 718 controls) a history of hypertension, using unconditional logistic and polytomous regression models. RESULTS: None of the antihypertensive drug types was associated with RCC overall. Among participants with a history of hypertension, papillary RCC was associated with long-term use of diuretics (OR = 3.1, 95% CI = 1.4-6.7 for 16+ years, 16 cases, 31 controls; P-trend = 0.014) and calcium channel blockers (OR = 2.8, 95% CI = 1.1-7.4 for 16+ years, 8 cases, 14 controls; P-trend = 0.18), while corresponding ORs for clear cell RCC were weaker (ORs 0.9 and 1.5, respectively) and nonsignificant. The only significant finding among those with no hypertension history was an association between calcium channel blockers and papillary RCC (OR = 17.9, 95% CI = 5.9-54.5) that was based on small numbers (8 cases, 9 controls). There was little evidence of an association between RCC and use of ACE inhibitors or beta blockers. CONCLUSIONS: Our study, while inconclusive for overall RCC, provides, to our knowledge, the first evidence supporting an association between antihypertensive medications and papillary RCC. These subtype-specific findings, although based on small numbers, warrant further investigation.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Carcinoma de Células Renais/etiologia , Hipertensão/tratamento farmacológico , Neoplasias Renais/etiologia , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
3.
Occup Environ Med ; 74(4): 268-274, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27803178

RESUMO

OBJECTIVES: Trichloroethylene, a chlorinated solvent widely used for metal degreasing, is classified by the International Agency for Research on Cancer as a kidney carcinogen. Other chlorinated solvents are suspected carcinogens, most notably the cleaning solvent perchloroethylene, although it is unclear whether they are associated with kidney cancer. We investigated kidney cancer associations with occupational exposure to 6 chlorinated solvents (trichloroethylene, perchloroethylene, 1,1,1-trichloroethane, carbon tetrachloride, chloroform, and methylene chloride) within a case-control study using detailed exposure assessment methods. METHODS: Cases (n=1217) and controls (n=1235) provided information on their occupational histories and, for selected occupations, on tasks involving potential exposure to chlorinated solvents through job-specific interview modules. Using this information, an industrial hygienist assessed potential exposure to each solvent. We computed ORs and 95% CIs for different exposure metrics, with unexposed participants as the referent group. RESULTS: 1,1,1-trichloroethane, carbon tetrachloride, chloroform, and methylene chloride were not associated with kidney cancer. Among jobs with high exposure intensity, high cumulative hours exposed to perchloroethylene was associated with increased risk, both overall (third tertile vs unexposed: OR 3.1, 95% CI 1.3 to 7.4) and after excluding participants with ≥50% exposure probability for trichloroethylene (OR 3.0, 95% CI 0.99 to 9.0). A non-significant association with high cumulative hours exposed to trichloroethylene was observed (OR 1.7, 95% CI 0.8 to 3.8). CONCLUSIONS: In this study, high exposure to perchloroethylene was associated with kidney cancer, independent of trichloroethylene. Additional studies are needed to further investigate this finding.


Assuntos
Hidrocarbonetos Clorados/efeitos adversos , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/epidemiologia , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/epidemiologia , Exposição Ocupacional/efeitos adversos , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Hidrocarbonetos Clorados/análise , Entrevistas como Assunto , Modelos Logísticos , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Solventes , Tetracloroetileno/efeitos adversos , Tetracloroetileno/análise , Tricloroetileno/efeitos adversos , Tricloroetileno/análise , Adulto Jovem
4.
Int J Cancer ; 138(7): 1626-33, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26505275

RESUMO

Epidemiological evidence of a relationship between vitamin D and kidney cancer risk has been inconsistent despite experimental data indicating that vitamin D and its metabolites may inhibit carcinogenesis. Previously we reported an inverse association between renal cell carcinoma (RCC) risk and occupational ultraviolet (UV) exposure among European men. In this study, we examined the association between occupational UV exposure and RCC risk among US residents and investigated whether this association varied by race and sex. Lifetime occupational data for 1,217 RCC cases and 1,235 controls in a population-based case-control study, conducted from 2002 to 2007, were assessed for occupational UV exposure. We evaluated exposure metrics in quartiles based on control exposure levels and calculated associations between RCC risk and occupational UV exposure using unconditional logistic regression adjusted for sex, race, body mass index, smoking, hypertension, center, education, family history of cancer and dietary vitamin D intake. A general pattern of decreasing RCC risk with increasing UV exposure was observed. Cases had significantly lower cumulative occupational UV exposure than controls (fourth quartile vs. first: odds ratio = 0.74 [95% confidence interval = 0.56-0.99], p-trend = 0.03). Similar results were observed for other UV exposure metrics. The association with occupational UV exposure was stronger for women than for men, but did not differ by race. Our findings suggest an inverse association between occupational UV exposure and RCC, particularly among women. Given the sex finding discrepancies in this study versus our previous study, additional research is need to clarify whether the protective effects of occupational UV exposure and RCC risk are real.


Assuntos
Carcinoma de Células Renais/epidemiologia , Neoplasias Renais/epidemiologia , Exposição Ocupacional/efeitos adversos , Luz Solar/efeitos adversos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Adulto Jovem
5.
Int J Cancer ; 139(3): 584-92, 2016 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-27009534

RESUMO

Analgesics are the most commonly consumed drugs worldwide. Evidence that analgesics increase kidney cancer risk has been mixed. We investigated the association between renal cell carcinoma (RCC) and analgesic use in a large population-based case-control study and a post-trial observational cohort study. Findings were used to update a recent meta-analytic review. We analyzed data from 1,217 RCC cases and 1,235 controls in the US Kidney Cancer Study and 98,807 participants in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO: n = 137 RCCs). Self-reported acetaminophen, aspirin and nonsteroid anti-inflammatory drug (NSAID) use and duration information was assessed in relation to RCC. For the US Kidney Cancer Study, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression. For PLCO, we computed hazard ratios (HRs) and 95%CIs using Cox regression. Among case-control participants, RCC risk was associated with over-the-counter acetaminophen use (OR = 1.35, 95%CI = 1.01-1.83). There was a positive trend with increasing duration (p-trend = 0.01), with a two-fold risk for use ≥10 years (OR = 2.01, 95%CI = 1.30-3.12). No association with prescription acetaminophen use was detected. In PLCO, acetaminophen use was also associated with increased RCC risk (HR = 1.68, 95%CI = 1.19-2.39), although elevated risk was absent among the few long-term users. No association with RCC risk was detected for aspirin or NSAIDs use in either study. An association between acetaminophen use and kidney cancer was supported by meta-analytic cohort (n = 4; summary relative risk = 1.34; 95%CI = 1.13-1.59; p-heterogeneity = 0.40) and case-control (n = 9, summary OR = 1.20; 95%CI = 1.01-1.42; p-heterogeneity = 0.05) findings. In brief, acetaminophen use may increase the risk of developing RCC.


Assuntos
Analgésicos/efeitos adversos , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/etiologia , Neoplasias Renais/epidemiologia , Neoplasias Renais/etiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Masculino , Razão de Chances , Risco , Estados Unidos/epidemiologia
6.
Am J Epidemiol ; 183(2): 85-91, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26656478

RESUMO

Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.


Assuntos
Glioma/genética , Cooperação Internacional , Epidemiologia Molecular/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Glioma/sangue , Glioma/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
7.
Cancer Causes Control ; 27(10): 1261-71, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27590306

RESUMO

PURPOSE: Previous studies assessing racial and ethnic differences in ovarian cancer (OVCA) diagnosis stage fail to present subtype-specific results and provide historic data on cases diagnosed between 10 and 20 years ago. The purpose of this analysis is to assess non-Hispanic Black (NHB) and non-Hispanic White (NHW) differences in late-stage diagnosis including; (1) factors associated with late-stage diagnosis of invasive epithelial OVCA overall and by histologic subtypes, (2) potential changes across time and (3) current patterns of trends in a national cancer registry in the USA and Puerto Rico between 1998 and 2011. METHODS: NHB and NHW OVCA cases were derived from the National Cancer Database (NCDB). Diagnosis stage was analyzed as a dichotomous and a four level-category variable, respectively; early (stages I and II; localized) versus late (stages III and IV; regional and distant) and stages I, II, III and IV. Diagnosis period was trichotomized (1998-2002, 2003-2007, 2008-2011). Racial differences in stage were tested using Chi-square statistics. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were estimated using multivariable binomial and generalized ordered logistic regressions. Interactions between race and diagnosis period were evaluated. RESULTS: Between 1998 and 2011, 11,562 (7.8 %) NHB and 137,106 (92.2 %) NHW were diagnosed with OVCA. In adjusted models, NHB were significantly more likely diagnosed with late-stage OVCA than NHW (ORadj 1.26, 95 % CI 1.19-1.33). Interaction between race and diagnosis period was marginally significant (p value = 0.09), with racial differences in stage decreasing over time (1998-2002: ORadj 1.36, 95 % CI 1.23-1.49; 2003-2007: ORadj 1.27, 95 % CI 1.15-1.39; 2008-2011; ORadj 1.15, 95 % CI 1.05-1.27). NHB were also more likely to be diagnosed with stage 4 high-grade serous (ORadj 1.46, 95 % CI 1.22-1.74), clear cell (ORadj 2.71, 95 % CI 1.94-3.79) and mucinous (ORadj 2.78, 95 % CI 2.24-3.46) carcinomas than NHW. CONCLUSIONS: Racial differences in late-stage OVCA diagnosis exist; however, these differences are decreasing with time. Within NCDB, NHB are significantly more likely diagnosed with late-stage OVCA and more specifically high-grade serous, clear cell and mucinous carcinomas than NHW.


Assuntos
Neoplasias Epiteliais e Glandulares/etnologia , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Carcinoma Epitelial do Ovário , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Porto Rico/epidemiologia , Fatores Socioeconômicos , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos
8.
Occup Environ Med ; 73(6): 417-24, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27102331

RESUMO

BACKGROUND: Mapping job titles to standardised occupation classification (SOC) codes is an important step in identifying occupational risk factors in epidemiological studies. Because manual coding is time-consuming and has moderate reliability, we developed an algorithm called SOCcer (Standardized Occupation Coding for Computer-assisted Epidemiologic Research) to assign SOC-2010 codes based on free-text job description components. METHODS: Job title and task-based classifiers were developed by comparing job descriptions to multiple sources linking job and task descriptions to SOC codes. An industry-based classifier was developed based on the SOC prevalence within an industry. These classifiers were used in a logistic model trained using 14 983 jobs with expert-assigned SOC codes to obtain empirical weights for an algorithm that scored each SOC/job description. We assigned the highest scoring SOC code to each job. SOCcer was validated in 2 occupational data sources by comparing SOC codes obtained from SOCcer to expert assigned SOC codes and lead exposure estimates obtained by linking SOC codes to a job-exposure matrix. RESULTS: For 11 991 case-control study jobs, SOCcer-assigned codes agreed with 44.5% and 76.3% of manually assigned codes at the 6-digit and 2-digit level, respectively. Agreement increased with the score, providing a mechanism to identify assignments needing review. Good agreement was observed between lead estimates based on SOCcer and manual SOC assignments (κ 0.6-0.8). Poorer performance was observed for inspection job descriptions, which included abbreviations and worksite-specific terminology. CONCLUSIONS: Although some manual coding will remain necessary, using SOCcer may improve the efficiency of incorporating occupation into large-scale epidemiological studies.


Assuntos
Indústrias/classificação , Descrição de Cargo , Processamento de Linguagem Natural , Ocupações/classificação , Algoritmos , Carcinoma de Células Renais , Estudos de Casos e Controles , Métodos Epidemiológicos , Estudos Epidemiológicos , Humanos , Modelos Logísticos , Reprodutibilidade dos Testes , Software , Estados Unidos , United States Occupational Safety and Health Administration
9.
Am J Physiol Cell Physiol ; 307(2): C150-61, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24808494

RESUMO

Thyroid hormones L-thyroxine (T4) and 3,3',5-triiodo-L-thyronine (T3) have been shown to initiate short- and long-term effects via a plasma membrane receptor site located on integrin αvß3. Also insulin-like growth factor type I (IGF-I) activity is known to be subject to regulation by this integrin. To investigate the possible cross-talk between T4 and IGF-I in rat L6 myoblasts, we have examined integrin αvß3-mediated modulatory actions of T4 on glucose uptake, measured through carrier-mediated 2-deoxy-[3H]-D-glucose uptake, and on cell proliferation stimulated by IGF-I, assessed by cell counting, [3H]-thymidine incorporation, and fluorescence-activated cell sorting analysis. IGF-I stimulated glucose transport and cell proliferation via the cell surface IGF-I receptor (IGFIR) and, downstream of the receptor, by the phosphatidylinositol 3-kinase signal transduction pathway. Addition of 0.1 nM free T4 caused little or no cell proliferation but prevented both glucose uptake and proliferative actions of IGF-I. These actions of T4 were mediated by an Arg-Gly-Asp (RGD)-sensitive pathway, suggesting the existence of crosstalk between IGFIR and the T4 receptor located near the RGD recognition site on the integrin. An RGD-sequence-containing integrin inhibitor, a monoclonal antibody to αvß3, and the T4 metabolite tetraiodothyroacetic acid all blocked the inhibition by T4 of IGF-I-stimulated glucose uptake and cell proliferation. Western blotting confirmed roles for activated phosphatidylinositol 3-kinase and extracellular regulated kinase 1/2 (ERK1/2) in the effects of IGF-I and also showed a role for ERK1/2 in the actions of T4 that modified the effects of IGF-I. We conclude that thyroid hormone inhibits IGF-I-stimulated glucose uptake and cell proliferation in L6 myoblasts.


Assuntos
Proliferação de Células/efeitos dos fármacos , Glucose/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Integrina alfaVbeta3/metabolismo , Mioblastos/metabolismo , Tiroxina/metabolismo , Animais , Transporte Biológico , Linhagem Celular , Regulação da Expressão Gênica/fisiologia , Fator de Crescimento Insulin-Like I/genética , Integrina alfaVbeta3/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais
10.
Hum Mol Genet ; 21(5): 1190-200, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-22113997

RESUMO

In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P = 5.75 × 10(-8), per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10(-14)) and rs12617313 (P = 7.48 × 10(-12)), both highly correlated with rs9679290 (r(2) > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r(2) < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10(-9), per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma de Células Renais/genética , Cromossomos Humanos Par 2/genética , Predisposição Genética para Doença , Neoplasias Renais/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Mapeamento Cromossômico , Feminino , Genótipo , Projeto HapMap , Haplótipos , Humanos , Masculino , Fumar
11.
Hum Mol Genet ; 21(2): 456-62, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-22010048

RESUMO

Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r(2) = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10(-10) and P = 6.07 × 10(-9), respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.


Assuntos
Carcinoma de Células Renais/genética , Cromossomos Humanos Par 12 , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Neoplasias Renais/genética , Humanos
12.
Annu Rev Pharmacol Toxicol ; 51: 99-115, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20868274

RESUMO

Plasma membrane integrin αvß3 is a cell surface receptor for thyroid hormone at which nongenomic actions are initiated. L-thyroxine (T4) and 3,3',5-triiodo-L-thyronine (T3) promote angiogenesis and tumor cell proliferation via the receptor. Tetraiodothyroacetic acid (tetrac), a deaminated T4 derivative, blocks the nongenomic proliferative and proangiogenic actions of T4 and T3. Acting at the integrin independently of T4 and T3, tetrac and a novel nanoparticulate formulation of tetrac that acts exclusively at the cell surface have oncologically desirable antiproliferative actions on multiple tumor cell survival pathway genes. These agents also block the angiogenic activity of vascular growth factors. Volume and vascular support of xenografts of human pancreatic, kidney, lung, and breast cancers are downregulated by tetrac formulations. The integrin αvß3 receptor site for thyroid hormone selectively regulates signal transduction pathways and distinguishes between unmodified tetrac and the nanoparticulate formulation. The receptor also mediates nongenomic thyroid hormone effects on plasma membrane ion transporters and on intracellular protein trafficking.


Assuntos
Integrina alfaVbeta3/metabolismo , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Humanos , Nanopartículas , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Transdução de Sinais , Tiroxina/administração & dosagem , Tiroxina/análogos & derivados , Tiroxina/farmacologia
13.
Cancer Causes Control ; 25(8): 1007-13, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24890803

RESUMO

PURPOSE: The association between female reproductive factors and glioma risk is unclear, but most published studies have been limited by small sample size. We conducted a pooled multisite study of pre- and postmenopausal women, investigating the effect of female reproductive factors, including hormonal medications. METHODS: Unconditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (95 % CIs) assessing the effects of female reproductive factors and female hormonal medications in glioma cases and unrelated controls. RESULTS: Menarche over the age of 15 as compared to under 12 was associated with a statistically significant risk for glioma (OR 2.00, 95 % CI 1.47-2.71). Use of oral contraceptive pills (OCP) was inversely associated with risk of glioma (OR 0.61, 95 % CI 0.50-0.74), and there was an inverse trend with longer duration of OCP use (p for trend <0.0001). Use of hormone replacement therapy (HRT) was also inversely associated with risk of glioma (OR 0.55, 95 % CI 0.44-0.68), and there was an inverse trend with longer duration of use (p for trend <0.0001). Compared to those reporting neither OCP use nor HRT use, those who reported using both were less likely to have a diagnosis of glioma (OR 0.34, 95 % CI 0.24-0.48). CONCLUSIONS: Female reproductive hormones may decrease the risk for glioma. The association appears to be strongest with greater length of use and use of both HRT and OCP.


Assuntos
Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/metabolismo , Anticoncepcionais Orais Hormonais/administração & dosagem , Glioma/epidemiologia , Glioma/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Terapia de Reposição Hormonal/estatística & dados numéricos , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
14.
Cancer Causes Control ; 25(5): 633-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24532025

RESUMO

PURPOSE: Higher pathologic grade, suboptimal debulking surgery, and late-stage are markers of more aggressive and advanced ovarian cancer. Neighborhood socioeconomic status (SES) has been associated with more aggressive and advanced tumors for other cancer sites, and this may also be true for ovarian cancer. METHODS: We examined the association between neighborhood SES and ovarian cancer tumor characteristics using data on 581 women diagnosed with epithelial ovarian cancer in Cook County, Illinois. Two complementary measures (concentrated disadvantage and concentrated affluence) were used to estimate neighborhood SES. Prevalence differences and 95 % confidence intervals were estimated in logistic regression models adjusted for age and race. RESULTS: Greater disadvantage was associated with higher grade tumors (p = 0.03) and suboptimal debulking (p = 0.05) and marginally associated with later tumor stage (p = 0.20). Greater affluence was inversely associated with stage at diagnosis (p = 0.004) and suboptimal debulking (p = 0.03) and (marginally) with tumor grade (p = 0.21). CONCLUSION: Our findings suggest that lower SES, estimated by neighborhood SES, is associated with ovarian cancer tumor characteristics indicative of more advanced and aggressive disease.


Assuntos
Neoplasias Epiteliais e Glandulares/economia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/economia , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Carcinoma Epitelial do Ovário , Feminino , Humanos , Illinois/epidemiologia , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Epiteliais e Glandulares/epidemiologia , Neoplasias Ovarianas/epidemiologia , Características de Residência/classificação , Fatores Socioeconômicos , Adulto Jovem
15.
BMC Cancer ; 14: 707, 2014 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-25253394

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) has a higher incidence in blacks than in whites. Physical activity may influence the risk of renal cell cancer, but the evidence is inconsistent. No previous study has investigated this relationship in the black population. METHODS: We examined the association between self-reported physical activity at different ages and risk of RCC in a population based case-control study of 1217 cases (361 black, 856 white) and 1235 controls (523 black, 712 white) frequency-matched on age, race, and gender. Multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression. RESULTS: Among whites, increased risks of RCC were observed among participants reporting low levels of transportation-related activity in their 20's (OR <1 hr/wk vs >7 hr/wk (95% CI): 1.42 (1.10, 1.83)) and leisure time activity in their 50's (OR <1 hr/wk vs >7 hr/wk (95% CI): 1.49 (1.00, 2.20)). We found no association between physical activity and RCC risk among blacks. CONCLUSION: Our results suggest that physical activity may be inversely associated with RCC risk in whites, but there was no evidence of such an association in blacks. As this is the first study evaluating the effect of physical activity on RCC risk among blacks, further investigations are needed to clarify the relationship in this population.


Assuntos
Negro ou Afro-Americano , Carcinoma de Células Renais/epidemiologia , Neoplasias Renais/epidemiologia , Atividade Motora , População Branca , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Fatores de Risco , Adulto Jovem
16.
FASEB J ; 27(8): 3209-16, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23640055

RESUMO

Thyroid hormone induces tumor cell and blood vessel cell proliferation via a cell surface receptor on heterodimeric integrin αvß3. We investigated the role of thyroid hormone-induced internalization of nuclear integrin αv monomer. Physiological concentration of thyroxine (free T4, 10(-10) M), but not 3,5,3'-triiodo-l-thyronine (T3), induced cellular internalization and nuclear translocation of integrin αv monomer in human non-small-cell lung cancer (H522) and ovarian carcinoma (OVCAR-3) cells. T4 did not complex with integrin αv monomer during its internalization. The αv monomer was phosphorylated by activated ERK1/2 when it heterodimerized with integrin ß3 in vitro. Nuclear αv complexed with transcriptional coactivator proteins, p300 and STAT1, and with corepressor proteins, NCoR and SMRT. Nuclear αv monomer in T4-exposed cells, but not integrin ß3, bound to promoters of specific genes that have important roles in cancer cells, including estrogen receptor-α, cyclooxygenase-2, hypoxia-inducible factor-1α, and thyroid hormone receptor ß1 in chromatin immunoprecipitation assay. In summary, monomeric αv is a novel coactivator regulated from the cell surface by thyroid hormone for the expression of genes involved in tumorigenesis and angiogenesis. This study also offers a mechanism for modulation of gene expression by thyroid hormone that is adjunctive to the nuclear hormone receptor (TR)-T3 pathway.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Integrina alfa5/metabolismo , Regiões Promotoras Genéticas/genética , Hormônios Tireóideos/farmacologia , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Endocitose/efeitos dos fármacos , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Humanos , Immunoblotting , Integrina alfa5/química , Integrina alfaVbeta3/química , Integrina alfaVbeta3/metabolismo , Integrina beta3/química , Integrina beta3/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patologia , Fosforilação/efeitos dos fármacos , Ligação Proteica , Multimerização Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT1/metabolismo , Tiroxina/farmacologia , Tri-Iodotironina/farmacologia , Fatores de Transcrição de p300-CBP/metabolismo
17.
Gynecol Oncol ; 135(2): 285-91, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25173584

RESUMO

BACKGROUND: Less than half of women with ovarian cancer and blacks specifically receive therapy adherent to National Comprehensive Cancer Network (NCCN) guidelines. The purpose is to assess the effect of neighborhood-level socioeconomic status (SES) on black-white treatment differences in a population-based analysis in a highly-segregated community. METHODS: Illinois State Cancer Registry data for invasive epithelial ovarian cancer cases diagnosed in Cook County, IL in non-Hispanic white (NHW) or black (NHB) women from 1998 to 2009 was analyzed. As few women receive NCCN-adherent care, variables were constructed to assess extent of treatment, including receipt of: 1) debulking surgery; 2) any surgery; 3) multi-agent chemotherapy; and 4) any chemotherapy. Two measures (concentrated affluence and disadvantage) were used to estimate neighborhood-level SES. Multivariable logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (95% CI), with generalized linear mixed models to account for hierarchical data. RESULTS: 2766 (81.0%) NHW and 647 (19.0%) NHB women were diagnosed. Adjusting for covariates, NHB were less likely to receive debulking surgery (OR: 0.39; 95% CI: 0.30-0.50), any surgery (OR: 0.38; 95%CI: 0.29-0.49), multi-agent chemotherapy (OR: 0.56; 95% CI: 0.45-0.71) and any chemotherapy (OR: 0.58; 95% CI: 0.45-0.74). Concentrated affluence but not disadvantage was significant in final models for multi-agent and any chemotherapy, but not debulking or any surgery. CONCLUSIONS: Results identify black-white differences consistent across treatments that persist despite adjustment for neighborhood-level SES. IMPACT: Results advance inequality awareness beyond "ideal" NCCN-adherent care, indicating inequality exists in delivery of even the most basic oncologic care.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Negro ou Afro-Americano/estatística & dados numéricos , Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Ovariectomia/estatística & dados numéricos , Características de Residência , Classe Social , População Branca/estatística & dados numéricos , Idoso , Carcinoma Epitelial do Ovário , Chicago , Métodos Epidemiológicos , Feminino , Fidelidade a Diretrizes , Humanos , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Exenteração Pélvica/estatística & dados numéricos , Guias de Prática Clínica como Assunto
18.
Occup Environ Med ; 71(12): 855-64, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24683012

RESUMO

OBJECTIVES: Growing evidence suggests that gender-blind assessment of exposure may introduce exposure misclassification, but few studies have characterised gender differences across occupations and industries. We pooled control responses to job-specific, industry-specific and exposure-specific questionnaires (modules) that asked detailed questions about work activities from three US population-based case-control studies to examine gender differences in work tasks and their frequencies. METHODS: We calculated the ratio of female-to-male controls that completed each module. For four job modules (assembly worker, machinist, health professional, janitor/cleaner) and for subgroups of jobs that completed those modules, we evaluated gender differences in task prevalence and frequency using χ(2) and Mann-Whitney U tests, respectively. RESULTS: The 1360 female and 2245 male controls reported 6033 and 12 083 jobs, respectively. Gender differences in female:male module completion ratios were observed for 39 of 45 modules completed by ≥20 controls. Gender differences in task prevalence varied in direction and magnitude. For example, female janitors were significantly more likely to polish furniture (79% vs 44%), while male janitors were more likely to strip floors (73% vs 50%). Women usually reported more time spent on tasks than men. For example, the median hours per week spent degreasing for production workers in product manufacturing industries was 6.3 for women and 3.0 for men. CONCLUSIONS: Observed gender differences may reflect actual differences in tasks performed or differences in recall, reporting or perception, all of which contribute to exposure misclassification and impact relative risk estimates. Our findings reinforce the need to capture subject-specific information on work tasks.


Assuntos
Indústrias , Exposição Ocupacional/análise , Ocupações , Fatores Sexuais , Trabalho , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Identidade de Gênero , Setor de Assistência à Saúde , Zeladoria , Humanos , Masculino , Indústria Manufatureira , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Inquéritos e Questionários , Adulto Jovem
19.
Support Care Cancer ; 22(5): 1349-62, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24382676

RESUMO

PURPOSE: Results from several studies suggest that there is value in evaluating the association between nonclinical characteristics of patients and quality of life (QoL), but few studies have focused on brain cancer. The primary goal of this feasibility study was to explore the relationship between clinical factors and nonclinical factors and QoL in brain cancer patients. METHODS: Participants in this cross-sectional study were drawn from two hospital sites. Eligible patients were 18-75 years old with a pathologically confirmed diagnosis of a brain cancer histology and stable disease after treatment. Data were obtained from medical chart review and a self-administered survey consisting of main study variables and two QoL standardized measures. Independent sample t test was used to determine differences between patient factors and QoL measures. RESULTS: The sample population was comprised of 26 patients with a median age at survey of 57.5 years (range 33-72). Quality of life was adversely associated with younger age, having underage children and living alone. Patients' meaning of QoL differed by gender, however most patients viewed it as affecting multiple aspects of their lives. CONCLUSIONS: Nonclinical characteristics were significantly associated with QoL more often than clinical characteristics. Identifying these factors may help improve the quality of care for these patients. This effort demonstrates the relevancy and feasibility of conducting a larger scale study to confirm or refute these findings.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/psicologia , Glioma/fisiopatologia , Glioma/psicologia , Adulto , Fatores Etários , Idoso , Neoplasias Encefálicas/patologia , Estudos Transversais , Estudos de Viabilidade , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Qualidade de Vida , Inquéritos e Questionários
20.
J Clin Endocrinol Metab ; 109(2): e870-e872, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-37624230

RESUMO

The prevalence of youth-onset type 2 diabetes is growing worldwide and current first-line treatment with metformin and intensive behavior and lifestyle changes are suboptimal in over 50% of youth within 2 years of diagnosis. This perspective article is a call to action for reevaluation of existing strategies and critical appraisal of metformin as first-line therapy in youth-onset type 2 diabetes. Increased attention should be given to novel therapeutics approved in youth, including glucagon-like 1 receptor agonists, sodium glucose cotransporter-2, and sociocultural interventions that will promote diabetes self-management.


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Humanos , Adolescente , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Metformina/uso terapêutico , Comportamentos Relacionados com a Saúde , Estilo de Vida
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