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1.
Artigo em Inglês | MEDLINE | ID: mdl-33619025

RESUMO

BACKGROUND: Androgen receptor signaling is crucial to prostate cancer aggressiveness. Members of the solute carrier family of the organic anion transporting peptides (SLCOs) are potential regulators of androgen availability in prostate tissue. It remains unknown whether genetic variations in SLCOs contribute to the differences in prostate cancer aggressiveness in African Americans (AAs) and European Americans (EAs). METHODS: Single nucleotide polymorphisms (SNPs) in 11 SLCO members were selected with addition of 139 potentially functional SNPs and 128 ancestry informative markers. A total of 1045 SNPs were genotyped and analyzed in 993 AAs and 1057 EAs from the North Carolina-Louisiana Prostate Cancer Project. Expression and cellular localization of SLCOs were examined using quantitative RT-PCR, immunohistochemistry, and in situ RNA hybridization in independent sets of prostate cancer cases. RESULTS: Significant associations with prostate cancer characteristics were found for SNPs in SLCO2A1 and SLCO5A1. The associations differed by race (P for interaction <0.05). SNPs in SLCO2A1 were associated with reduced tumor aggressiveness and low Gleason score in AAs; whereas, SNPs in SLCO5A1 were associated with high clinical stage in EAs. In prostate tissue, SLCO2A1 and SLCO5A1 were the most expressed SLCOs at the mRNA level and were expressed predominantly in prostate endothelial and epithelial cells at the protein level, respectively. CONCLUSIONS: SLCO2A1 and SLCO5A1 play important but different roles in prostate cancer aggressiveness in AAs versus EAs. IMPACT: The finding calls for consideration of racial differences in biomarker studies of prostate cancer and for investigations on functions of SLCO2A1 and SLCO5A1 in prostate cancer.

2.
Int J Cancer ; 148(1): 99-105, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32930425

RESUMO

Polygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46) showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify single nucleotide polymorphisms (SNPs) that might improve performance in this population. Anonymized genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Ten iterations of a 10-fold cross-validation search were conducted to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African was compared using the same cross-validated approach. Three SNPs (rs76229939, rs74421890 and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located on chromosome 8q24. PHS46+African showed substantial improvements in all performance metrics measured, including a 75% increase in the relative hazard of those in the upper 20% compared to the bottom 20% (2.47-4.34) and a 20% reduction in the relative hazard of those in the bottom 20% compared to the middle 40% (0.65-0.53). In conclusion, we identified three SNPs that substantially improved the association of PHS46 with age at diagnosis of prostate cancer in men with African genetic ancestry to levels comparable to Europeans.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33198142

RESUMO

High-level exposure to arsenic, a known carcinogen and endocrine disruptor, is associated with prostate cancer (PCa) mortality. Whether low-level exposure is associated with PCa aggressiveness remains unknown. We examined the association between urinary arsenic and PCa aggressiveness among men in North Carolina. This cross-sectional study included 463 African-American and 491 European-American men with newly diagnosed, histologically confirmed prostate adenocarcinoma. PCa aggressiveness was defined as low aggressive (Gleason score < 7, stage = cT1-cT2, and PSA < 10 ng/mL) versus intermediate/high aggressive (all other cases). Total arsenic and arsenical species (inorganic arsenic (iAsIII + iAsV), arsenobetaine, monomethyl arsenic, and dimethyl arsenic)) and specific gravity were measured in spot urine samples obtained an average of 23.7 weeks after diagnosis. Multivariable logistic regression was used to estimate the covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for PCa aggressiveness in association with arsenic tertiles/quantiles overall and by race. The highest (vs. lowest) tertile of total arsenic was associated with PCa aggressiveness ORs of 1.77 (95% CI = 1.05-2.98) among European-American men, and 0.94 (95% CI = 0.57-1.56) among African-American men (PInteraction = 0.04). In contrast, total arsenic and arsenical species were not associated with PCa aggressiveness in unstratified models. Low-level arsenic exposure may be associated with PCa aggressiveness among European-Americans, but not among African-Americans.

4.
Biomolecules ; 10(10)2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33007922

RESUMO

Prostate cancer (PCa) is the most common male cancer and the second leading cause of cancer death in United States men. Controversy continues over the effectiveness of prostate-specific antigen (PSA) for distinguishing aggressive from indolent PCa. There is a critical need for more specific and sensitive biomarkers to detect and distinguish low- versus high-risk PCa cases. Discovery metabolomics were performed utilizing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) on plasma samples from 159 men with treatment naïve prostate cancer participating in the North Carolina-Louisiana PCa Project to determine if there were metabolites associated with aggressive PCa. Thirty-five identifiable plasma small molecules were associated with PCa aggressiveness, 15 of which were sphingolipids; nine common molecules were present in both African-American and European-American men. The molecules most associated with PCa aggressiveness were glycosphingolipids; levels of trihexosylceramide and tetrahexosylceramide were most closely associated with high-aggressive PCa. The Cancer Genome Atlas was queried to determine gene alterations within glycosphingolipid metabolism that are associated with PCa and other cancers. Genes that encode enzymes associated with the metabolism of glycosphingolipids were altered in 12% of PCa and >30% of lung, uterine, and ovarian cancers. These data suggest that the identified plasma (glyco)sphingolipids should be further validated for their association with aggressive PCa, suggesting that specific sphingolipids may be included in a diagnostic signature for PCa.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32960377

RESUMO

PURPOSE: Circulating anti-Müllerian hormone (AMH) levels are positively associated with time to menopause and breast cancer risk. We examined breast cancer associations with single nucleotide polymorphisms (SNPs) in the AMH gene or its receptor genes, ACVR1 and AMHR2, among African American women. METHODS: In the AMBER consortium, we tested 65 candidate SNPs, and 1130 total variants, in or near AMH, ACVR1, and AMHR2 and breast cancer risk. Overall, 3649 cases and 4230 controls contributed to analyses. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were calculated using multivariable logistic regression. RESULTS: After correction for multiple comparisons (false-discovery rate of 5%), there were no statistically significant associations with breast cancer risk. Without correction for multiple testing, four candidate SNPs in ACVR1 and one near AMH were associated with breast cancer risk. In ACVR1, rs13395576[C] was associated with lower breast cancer risk overall (OR 0.84; 95% CI 0.72, 0.97) and for ER+ disease (OR 0.75; CI 0.62, 0.89) (p < 0.05). Rs1220110[A] and rs1220134[T] each had ORs of 0.89-0.90 for postmenopausal and ER+ breast cancer (p ≤ 0.03). Conversely, rs1682130[T] was associated with higher risk of ER+ breast cancer (OR 1.17; 95% CI 1.04, 1.32). Near AMH, rs6510652[T] had ORs of 0.85-0.90 for breast cancer overall and after menopause (p ≤ 0.02). CONCLUSIONS: The present results, from a large study of African American women, provide limited support for an association between AMH-related polymorphisms and breast cancer risk and require replication in other studies.

6.
Eur Urol ; 78(3): 316-320, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32409115

RESUMO

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13-7.22) and 33.41 (95% CI = 10.86-102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17-25%) for TA heterozygotes and 38% (95% CI = 13-65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. PATIENT SUMMARY: We found that rs72725854, an African ancestry-specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening.

7.
Prostate ; 80(8): 609-618, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32168400

RESUMO

BACKGROUND: Using a functional analysis of prostate cancer cells, we found a CD24-dependent inactivation of mutant p53, but the clinical significance of this observation remained uncertain. Here, we validated these results with samples of human prostate cancer and explored the role of a CD24-p53 axis in racial disparities of prostate cancer. METHODS: Samples of formalin-fixed, paraffin-embedded prostate cancer from 141 European Americans (EAs) and 147 African Americans (AAs) in two independent sample cohorts were assessed for protein expression of CD24, mutant p53, mouse double minute 2 human homolog (MDM2), and cyclin dependent kinase inhibitor 2A (ARF) using immunohistochemical analyses. All samples were analyzed for TP53R175H and TP53R273H . RESULTS: CD24, mutant p53, MDM2, and ARF proteins were expressed in 55%, 24%, 39%, and 68% of prostate cancer samples, respectively. CD24 and mutant p53 were present more frequently in late-stage and metastatic prostate cancer. The presence of CD24 was associated with a greater than fourfold risk of metastasis, which included lymph node and distant metastases. H score analysis showed positive correlations of CD24 expression with mutant p53 (r = .308, P < .001) and MDM2 (r = .227, P = .004). There was a negative correlation for CD24 with ARF (r = -.280, P < .001). A racial disparity was evident for CD24 (AAs/EAs: 64% vs 47%; P = .004) but not for mutant p53 (AA/EA: 28% vs 21%; P = .152). In 32 CD24+ /mutant p53+ cases, a TP53R273H mutation was found in five cases, but no TP53R175H mutation was found. CONCLUSION: The CD24-p53 axis may contribute to aggressive and metastatic prostate cancers, especially those of AAs. This observation enhances understanding of the pathogenesis of prostate cancer and its associated racial disparities.


Assuntos
Afro-Americanos/genética , Antígeno CD24/genética , Neoplasias da Próstata/genética , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Antígeno CD24/biossíntese , Antígeno CD24/metabolismo , Grupo com Ancestrais do Continente Europeu/genética , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Metástase Neoplásica , Estadiamento de Neoplasias , Inclusão em Parafina , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transdução de Sinais , Fixação de Tecidos , Proteína Supressora de Tumor p53/biossíntese , Proteína Supressora de Tumor p53/metabolismo
8.
Int J Cancer ; 147(3): 876-886, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31837003

RESUMO

Laboratory studies have observed chemopreventive effects of black and green tea on breast cancer development, but few epidemiologic studies have identified such effects. We investigated the association between tea consumption and breast cancer risk using data from 45,744 U.S. and Puerto Rican women participating in the Sister Study. Frequency and serving size of black and green tea consumption were measured at cohort enrollment. Breast cancer diagnoses were reported during follow-up and confirmed by medical record review. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We further investigated potential variation according to estrogen receptor (ER) status, menopausal status and body mass index (BMI). Overall, 81.6 and 56.0% of women drank black or green tea, respectively. A total of 2,809 breast cancer cases were identified in the cohort. The multivariable model suggested an inverse association between black (≥5 vs. 0 cups/week: HR = 0.88, 95% CI 0.78, 1.00, p-trend = 0.08) and green tea (≥5 vs. 0 cups/week: HR = 0.82, 95% CI 0.70, 0.95, p-trend < 0.01) consumption and breast cancer risk. We did not observe differences by ER characteristics, menopausal status or BMI. In conclusion, our study suggests drinking at least five cups of green or black tea per week may be associated with decreased breast cancer risk.

9.
Cancer ; 125(19): 3418-3427, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31246284

RESUMO

BACKGROUND: The early diagnosis and treatment of depression are cancer care priorities. These priorities are critical for prostate cancer survivors because men rarely seek mental health care. However, little is known about the epidemiology of depression in this patient population. The goal of this study was to describe the prevalence and predictors of probable depression in prostate cancer survivors. METHODS: The data were from a population-based cohort of North Carolinian prostate cancer survivors who were enrolled from 2004 to 2007 in the North Carolina-Louisiana Prostate Cancer Project (n = 1031) and were prospectively followed annually from 2008 to 2011 in the Health Care Access and Prostate Cancer Treatment in North Carolina study (n = 805). Generalized estimating equations were used to evaluate an indicator of probable depression (Short Form 12 mental composite score ≤48.9; measured at enrollment and during the annual follow-up) as a function of individual-level characteristics within the longitudinal data set. RESULTS: The prevalence of probable depression fell from 38% in the year of the cancer diagnosis to 20% 6 to 7 years later. Risk factors for probable depression throughout the study were African American race, unemployment, low annual income, younger age, recency of cancer diagnosis, past depression, comorbidities, treatment decisional regret, and nonadherence to exercise recommendations. CONCLUSIONS: Depression is a major challenge for prostate cancer survivors, particularly in the first 5 years after the cancer diagnosis. To the authors' knowledge, this is the first study to demonstrate an association between treatment decisional regret and probable depression.


Assuntos
Sobreviventes de Câncer/psicologia , Depressão/epidemiologia , Neoplasias da Próstata/psicologia , Qualidade de Vida/psicologia , Adulto , Afro-Americanos/psicologia , Afro-Americanos/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Sobreviventes de Câncer/estatística & dados numéricos , Tomada de Decisões , Depressão/diagnóstico , Depressão/etiologia , Depressão/psicologia , Emoções , Grupo com Ancestrais do Continente Europeu/psicologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Seguimentos , Humanos , Louisiana/epidemiologia , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Cooperação do Paciente/psicologia , Prevalência , Probabilidade , Estudos Prospectivos , Próstata , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Fatores de Risco , Desemprego/psicologia , Desemprego/estatística & dados numéricos
10.
Prostate ; 79(10): 1117-1124, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31077420

RESUMO

BACKGROUND: African-American (AA) men tend to present with more aggressive prostate cancer (Gleason score >7) than European-American (EA) men. Vitamin D and its metabolites are implicated in prostate cancer biology with vitamin D deficiency, indicated by its metabolite levels in serum or plasma, usually observed in AA men. OBJECTIVE: To determine if 1, 25-dihydroxy vitamin D3 [1,25(OH)2 D] plasma levels in AA and EA prostate cancer patients alter the risk of having aggressive prostate cancer. DESIGN: Research subjects from the North Carolina-Louisiana Prostate Cancer Project (AA n = 435 and EA n = 532) were included. Plasma metabolites 1,25(OH)2 D and 25-hydroxyvitamin D3 [25(OH)D] were measured using liquid chromatography with tandem mass spectrophotometry. Research subjects were classified into low (Gleason sum < 7, stage T1-T2, and Prostate-specific antigen (PSA) < 9 ng/mL) or high (Gleason sum > 8 or Gleason sum = 7 with 4 + 3, or PSA > 20 ng/mL, or Gleason sum = 7 and stage T3-T4) aggressive disease. RESULTS: Research subjects in the second and third tertiles of plasma levels of 1, 25(OH)2 D had lower odds of high aggressive prostate cancer (AA [ORT2vsT1 : 0.66, 95%CI: 0.39-1.12; ORT3vsT1 : 0.83, 95%CI: 0.49-1.41] and EA [ORT2vsT1 : 0.68, 95%CI: 0.41-1.11; ORT3vsT1 : 0.67, 95%CI: 0.40-1.11]) compared with the first tertile, though confidence intervals included the null. Greater 1,25(OH)2 D/25(OH)D molar ratios were associated with lower odds of high aggressive prostate cancer more evidently in AA (ORQ4vsQ1 : 0.45, CI: 0.24-0.82) than in EA (ORQ4vsQ1 : 0.64, CI: 0.35-1.17) research subjects. CONCLUSIONS: The 1,25(OH)2 D/25(OH)D molar ratio was associated with decreased risk of high aggressive prostate cancer in AA men, and possibly in EA men. Further studies analyzing vitamin D polymorphisms, vitamin D binding protein levels, and prostatic levels of these metabolites may be useful. These studies may provide a better understanding of the vitamin D pathway and its biological role underlying health disparities in prostate cancer.


Assuntos
Calcitriol/sangue , Invasividade Neoplásica/patologia , Próstata/patologia , Neoplasias da Próstata/sangue , Vitamina D/análogos & derivados , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/patologia , Fatores de Risco , Vitamina D/sangue
11.
Cancer Med ; 8(8): 3648-3658, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31106980

RESUMO

BACKGROUND: Appropriate depression care is a cancer-care priority. However, many cancer survivors live with undiagnosed and untreated depression. Prostate cancer survivors may be particularly vulnerable, but little is known about their access to depression care. The goal of this study was to describe patterns and predictors of clinical diagnosis and treatment of depression in prostate cancer survivors. METHODS: Generalized estimating equations were used to evaluate indicators of self-reported clinical diagnosis and treatment depression as a function of individual-level characteristics within a longitudinal dataset. The data were from a population-based cohort of North Carolinian prostate cancer survivors who were enrolled from 2004 to 2007 on the North Carolina-Louisiana Prostate Cancer Project (N = 1,031), and prospectively followed annually from 2008 to 2011 on the Health Care Access and Prostate Cancer Treatment in North Carolina (N = 805). RESULTS: The average rate of self-reported clinical diagnosis of depression was 44% (95% CI: 39%-49%), which declined from 60% to 40% between prostate cancer diagnosis and 5-7 years later. Factors associated with lower odds of self-reported clinical diagnosis of depression include African-American race, employment, age at enrollment, low education, infrequent primary care visits, and living with a prostate cancer diagnosis for more than 2 years. The average rate of self-reported depression treatment was 62% (95% CI: 55%-69%). Factors associated with lower odds of self-reported depression treatment included employment and living with a prostate cancer diagnosis for 2 or more years. CONCLUSION: Prostate cancer survivors experience barriers when in need of depression care.


Assuntos
Sobreviventes de Câncer/psicologia , Depressão/epidemiologia , Depressão/etiologia , Padrões de Prática Médica , Neoplasias da Próstata/complicações , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Depressão/diagnóstico , Depressão/terapia , Gerenciamento Clínico , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Prognóstico , Vigilância em Saúde Pública , Autorrelato , Inquéritos e Questionários
12.
Support Care Cancer ; 27(7): 2693-2698, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30484012

RESUMO

PURPOSE: In older women, breast cancer and its treatment can have profound impact on their physical, mental, and social health, especially in frail patients. This study evaluated the association between frailty and long-term health-related quality of life (HRQOL) in older women undergoing breast cancer treatment. METHODS: Using the Carolina Senior Registry (CSR), participants with breast cancer were contacted to complete a follow-up HRQOL questionnaire (median 4 years). Baseline Geriatric Assessment (GA) variables were used to calculate the Carolina Frailty Index (CFI) and categorize participants as robust, pre-frail, or frail. Outcomes included HRQOL domains of physical function, social roles, fatigue, depression, anxiety, pain, and sleep disturbance assessed using PROMIS® instruments. Regression modeling compared outcomes between frailty groups using adjusted mean differences (AMD). RESULTS: Of 190 eligible patients, 63 completed follow-up HRQOL survey. Mean age was 70 years (range 65-86) and 91% were white. Based on the CFI, 49 (78%) patients were robust, 11 (18%) pre-frail, and 3 (5%) frail. After controlling for age and cancer stage, patients identified as pre-frail/frail reported worse physical function (AMD - 9.2, p < 0.001) and social roles (AMD - 7.2, p = 0.002) and more fatigue (AMD 7.6, p = 0.008), depression (AMD 5.6, p = 0.004), and sleep disturbance (AMD 6.9, p = 0.008) compared to robust patients at follow-up. CONCLUSIONS: Frailty in older women with breast cancer was associated with worse long-term HRQOL outcomes. Further research is needed to develop interventions for frail patients at-risk for reduced HRQOL.


Assuntos
Neoplasias da Mama/fisiopatologia , Neoplasias da Mama/psicologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Ansiedade/epidemiologia , Ansiedade/fisiopatologia , Ansiedade/psicologia , Neoplasias da Mama/epidemiologia , Depressão/epidemiologia , Depressão/fisiopatologia , Depressão/psicologia , Fadiga/epidemiologia , Fadiga/fisiopatologia , Fadiga/psicologia , Feminino , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/epidemiologia , Fragilidade/fisiopatologia , Fragilidade/psicologia , Avaliação Geriátrica , Humanos , Masculino , North Carolina/epidemiologia , Qualidade de Vida , Sistema de Registros , Inquéritos e Questionários
13.
Cancer Chemother Pharmacol ; 83(1): 61-70, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30327876

RESUMO

PURPOSE: Obesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer. METHODS: Hormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured. A separate pharmacology study was performed that evaluated the relationship between serum hormone concentrations, MPS function, and PK disposition of PLD in refractory ovarian cancer patients. RESULTS: Univariate analysis revealed a significant relationship between serum estradiol and body mass index (OR 8.64, 95% CI 2.67-28.0, p < 0.001). Estrone and testosterone concentrations were positively correlated with MPS function (ρ = 0.57 and 0.53, p = 0.14 and 0.18, respectively) and inversely correlated with PLD PK exposure (ρ = - 0.75 and - 0.76, respectively, p = 0.02 for both). CONCLUSIONS: Higher MPS function resulting in reduced PLD exposure is a potential mechanism for reduced efficacy of PLD and other nanoparticles observed in obese patients with cancer. PK simulations suggest higher doses of PLD are required in obese patients to achieve similar exposures as standard dosing in normal weight patients.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/análogos & derivados , Neoplasias do Endométrio/patologia , Sistema Fagocitário Mononuclear/fisiopatologia , Nanopartículas/administração & dosagem , Obesidade/fisiopatologia , Neoplasias Ovarianas/patologia , Antibióticos Antineoplásicos/química , Estudos de Casos e Controles , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Nanopartículas/química , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Prognóstico
14.
Ann Epidemiol ; 29: 16-22.e1, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30268488

RESUMO

BACKGROUND: Several foods and nutrients have been linked to the development of prostate cancer, but the association between healthy dietary patterns and prostate cancer aggressiveness is less studied. The aim of this study was to evaluate the relationship between the Mediterranean diet (MED) and Dietary Approaches to Stop Hypertension (DASH) diet scores and prostate cancer aggressiveness by race. METHODS: Data from the population-based, case-only North Carolina-Louisiana Prostate Cancer Project (PCaP) were used to examine the association between diet quality, measured by MED and DASH scores, and prostate cancer aggressiveness in 1899 African American (AA) and European American (EA) research subjects. Dietary intake was assessed using a modified National Cancer Institute Diet History Questionnaire. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for high versus low-intermediate aggressive prostate cancer. RESULTS: Higher MED scores were inversely associated with high aggressive prostate cancer overall (OR: 0.66; 95% CI: 0.46, 0.95 for high versus low scores); results were similar for AA and EA men. A weaker inverse association between DASH scores and prostate cancer aggressiveness was found (OR: 0.76; 95% CI: 0.55, 1.06). CONCLUSIONS: Higher diet quality, as represented by a Mediterranean-style diet or DASH diet, may reduce the odds of high aggressive prostate cancer.


Assuntos
Afro-Americanos , Dieta Mediterrânea , Abordagens Dietéticas para Conter a Hipertensão , Grupo com Ancestrais do Continente Europeu , Invasividade Neoplásica/patologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Estudos Transversais , Humanos , Incidência , Louisiana/epidemiologia , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Vigilância da População , Neoplasias da Próstata/etnologia
16.
J Oncol Pract ; : JOP1800120, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355027

RESUMO

PURPOSE:: Because of the escalating cost of cancer care coupled with high insurance deductibles, premiums, and uninsured populations, patients with cancer are affected by treatment-related financial harm, known as financial toxicity. The purpose of this study was to describe individuals reporting financial toxicity and to identify rates of and reasons for affordability-related treatment noncompliance. METHODS:: From May 2010 to November 2015, adult patients (age ≥ 18 years) with cancer were identified from a Health Registry/Cancer Survivorship Cohort. Financial toxicity was defined as agreement with the phrase "You have to pay for more medical care than you can afford" from the Patient Satisfaction Questionnaire-18. Logistic regression and Fisher exact tests were used to compare groups. RESULTS:: Of 1,988 participants, 524 (26%) reported financial toxicity. Patients reporting financial toxicity were more likely age 65 years or younger, female, nonwhite, non-English speaking, not married, less educated, and to have received a diagnosis more recently (all P < .001). Participants with financial toxicity were more likely to report noncompliance with medication, owing to inability to afford prescription drugs (relative risk [RR], 3.55; 95% CI, 2.53 to 4.98), and reported forgoing mental health care (RR, 3.89; 95% CI, 2.04 to 7.45), doctor's visits (RR, 2.98; 95% CI, 1.97 to 4.51), and medical tests (RR, 2.54; 95% CI, 1.49 to 4.34). The most endorsed reasons for delayed care were not having insurance coverage and being unable to afford household expenses. CONCLUSION:: More than 25% of adults with cancer reported financial toxicity that was associated with an increased risk for medical noncompliance. Financial toxicity remains a major issue in cancer care, and efforts are needed to ensure patients experiencing high levels of financial toxicity are able to access recommended care.

17.
Am J Hum Genet ; 103(3): 319-327, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30193136

RESUMO

The Clinical Sequencing Evidence-Generating Research (CSER) consortium, now in its second funding cycle, is investigating the effectiveness of integrating genomic (exome or genome) sequencing into the clinical care of diverse and medically underserved individuals in a variety of healthcare settings and disease states. The consortium comprises a coordinating center, six funded extramural clinical projects, and an ongoing National Human Genome Research Institute (NHGRI) intramural project. Collectively, these projects aim to enroll and sequence over 6,100 participants in four years. At least 60% of participants will be of non-European ancestry or from underserved settings, with the goal of diversifying the populations that are providing an evidence base for genomic medicine. Five of the six clinical projects are enrolling pediatric patients with various phenotypes. One of these five projects is also enrolling couples whose fetus has a structural anomaly, and the sixth project is enrolling adults at risk for hereditary cancer. The ongoing NHGRI intramural project has enrolled primarily healthy adults. Goals of the consortium include assessing the clinical utility of genomic sequencing, exploring medical follow up and cascade testing of relatives, and evaluating patient-provider-laboratory level interactions that influence the use of this technology. The findings from the CSER consortium will offer patients, healthcare systems, and policymakers a clearer understanding of the opportunities and challenges of providing genomic medicine in diverse populations and settings, and contribute evidence toward developing best practices for the delivery of clinically useful and cost-effective genomic sequencing in diverse healthcare settings.


Assuntos
Genoma Humano/genética , Adulto , Análise Custo-Benefício/métodos , Assistência à Saúde/métodos , Europa (Continente) , Exoma/genética , Genômica/métodos , Humanos , National Human Genome Research Institute (U.S.) , Fenótipo , Estados Unidos , Sequenciamento Completo do Genoma/métodos
18.
Cancer Causes Control ; 29(11): 1143-1150, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30267174

RESUMO

PURPOSE: Metformin has been associated with a reduced incidence of prostate cancer and improved prostate cancer outcomes. However, whether race modifies the association between metformin use and prostate cancer aggressiveness remains uncertain. The association between metformin use and prostate cancer aggressiveness was examined separately in Black Americans (Blacks) and White Americans (Whites). METHODS: The study population consisted of 305 Black and 195 White research participants with incident prostate cancer and self-reported diabetes from the North Carolina-Louisiana Prostate Cancer Project. High-aggressive prostate cancer was defined using a composite measure of Gleason sum, prostate-specific antigen, and clinical stage. Multivariable logistic regression was used to assess the association between metformin use and high-aggressive prostate cancer at diagnosis, separately among Whites and Blacks, with adjustment for age, screening history, site, education, insurance, and body mass index. RESULTS: Metformin use was associated positively with high-aggressive prostate cancer in Blacks (OR 2.01; 95% CI 1.05, 3.83). By contrast, a weak inverse association between metformin use and high-aggressive prostate cancer was found in Whites (OR 0.80, 95% CI 0.34, 1.85). CONCLUSIONS: The association between metformin use and prostate cancer aggressiveness may be modified by race.


Assuntos
Afro-Americanos/etnologia , Diabetes Mellitus/tratamento farmacológico , Grupo com Ancestrais do Continente Europeu/etnologia , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/patologia , Adulto , Idoso , Índice de Massa Corporal , Complicações do Diabetes/etnologia , Humanos , Incidência , Louisiana/epidemiologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , North Carolina/epidemiologia , Antígeno Prostático Específico , Neoplasias da Próstata/complicações , Fatores Raciais , Autorrelato , Estados Unidos/epidemiologia
19.
Breast Cancer Res ; 20(1): 45, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29871690

RESUMO

BACKGROUND: MicroRNAs (miRNAs) regulate gene expression and influence cancer. Primary transcripts of miRNAs (pri-miRNAs) are poorly annotated and little is known about the role of germline variation in miRNA genes and breast cancer (BC). We sought to identify germline miRNA variants associated with BC risk and tumor subtype among African-American (AA) women. METHODS: Under the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium, genotyping and imputed data from four studies on BC in AA women were combined into a final dataset containing 224,188 miRNA gene single nucleotide polymorphisms (SNPs) for 8350 women: 3663 cases and 4687 controls. The primary miRNA sequence was identified for 566 miRNA genes expressed in Encyclopedia of DNA Elements (ENCODE) Tier 1 cell types and human pancreatic islets. Association analysis was conducted using logistic regression for BC status overall and by tumor subtype. RESULTS: A novel BC signal was localized to an 8.6-kb region of 17q25.3 by four SNPs (rs9913477, rs1428882938, rs28585511, and rs7502931) and remained statistically significant after multiple test correction (odds ratio (OR) = 1.44, 95% confidence interval (CI) = 1.26-1.65; p = 3.15 × 10-7; false discovery rate (FDR) = 0.03). These SNPs reside in a genomic location that includes both the predicted primary transcript of the noncoding miRNA gene MIR3065 and the first intron of the gene for brain-specific angiogenesis inhibitor 1-associated protein 2 (BAIAP2). Furthermore, miRNA-associated SNPs on chromosomes 1p32.3, 5q32, and 3p25.1 were the strongest signals for hormone receptor, luminal versus basal-like, and HER2 enrichment status, respectively. A second phase of genotyping (1397 BC cases, 2418 controls) that included two SNPs in the 8.6-kb region was used for validation and meta-analysis. While neither rs4969239 nor rs9913477 was validated, when meta-analyzed with the original dataset their association with BC remained directionally consistent (OR = 1.29, 95% CI = 1.16-1.44 (p = 4.18 × 10-6) and OR = 1.33, 95% CI = 1.17-1.51 (p = 1.6 × 10-5), respectively). CONCLUSION: Germline genetic variation indicates that MIR3065 may play an important role in BC development and heterogeneity among AA women. Further investigation to determine the potential functional effects of these SNPs is warranted. This study contributes to our understanding of BC risk in AA women and highlights the complexity in evaluating variation in gene-dense regions of the human genome.


Assuntos
Neoplasias da Mama/genética , Estudos de Associação Genética , Predisposição Genética para Doença , MicroRNAs/genética , Afro-Americanos/genética , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Genoma Humano/genética , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor ErbB-2/genética
20.
BMC Med Res Methodol ; 18(1): 60, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29925318

RESUMO

BACKGROUND: Attrition occurs when a participant fails to respond to one or more study waves. The accumulation of attrition over several waves can lower the sample size and power and create a final sample that could differ in characteristics than those who drop out. The main reason to conduct a longitudinal study is to analyze repeated measures; research subjects who drop out cannot be replaced easily. Our group recently investigated factors affecting nonparticipation (refusal) in the first wave of a population-based study of prostate cancer. In this study we assess factors affecting attrition in the second wave of the same study. We compare factors affecting nonparticipation in the second wave to the ones affecting nonparticipation in the first wave. METHODS: Information available on participants in the first wave was used to model attrition. Different sources of attrition were investigated separately. The overall and race-stratified factors affecting attrition were assessed. Kaplan-Meier survival curve estimates were calculated to assess the impact of follow-up time on participation. RESULTS: High cancer aggressiveness was the main predictor of attrition due to death or frailty. Higher Charlson Comorbidity Index increased the odds of attrition due to death or frailty only in African Americans (AAs). Young age at diagnosis for AAs and low income for European Americans (EAs) were predictors for attrition due to lost to follow-up. High cancer aggressiveness for AAs, low income for EAs, and lower patient provider communication scores for EAs were predictors for attrition due to refusal. These predictors of nonparticipation were not the same as those in wave 1. For short follow-up time, the participation probability of EAs was higher than that of AAs. CONCLUSIONS: Predictors of attrition can vary depending on the attrition source. Examining overall attrition (combining all sources of attrition under one category) instead of distinguishing among its different sources should be avoided. The factors affecting attrition in one wave can be different in a later wave and should be studied separately.


Assuntos
Modelos Logísticos , Participação do Paciente/estatística & dados numéricos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Adulto , Afro-Americanos/estatística & dados numéricos , Idoso , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Participação do Paciente/psicologia , Neoplasias da Próstata/etnologia , Fatores de Risco , Estados Unidos
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