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1.
Artigo em Inglês | MEDLINE | ID: mdl-33772705

RESUMO

PURPOSE: We examined gut microbiome (GM) profiles in relation to mammographic breast density (BD) and body mass index (BMI) in healthy postmenopausal women. METHODS: Eligible women were postmenopausal, had a BMI ≤ 35 kg/m2, and had not recently taken oral/IV antibiotics. All women provided a fecal sample and information on breast cancer risk factors. Mammographic BD was classified with the American College of Radiology's BI-RADS BD classification system. Bacterial DNA was isolated from fecal samples and the V1-V2 hypervariable regions of 16S rRNA were sequenced on the Illumina MiSeq platform. We examined associations of GM with indices of within-sample (alpha) diversity and the ratio of the two main phyla (Firmicutes and Bacteroidetes; F/B ratio) with BD and BMI. RESULTS: Among 69 women with BD data, 39 had low BD (BI-RADS I/II) and 30 had high BD (BI-RADS III/IV). BMI was inversely associated with BD (mean BMI = 23.8 and 28.0 in women with high and low BD, respectively, p = 1.07 × 10-5). Similar levels of GM diversity were found across weight groups according to Shannon (p = 0.83); Inverse Simpson (p = 0.97); and Chao1 (p = 0.31) indices. F/B ratio and microbiota diversity were suggestively greater in women with high vs. low BD (p = 0.35, 0.14, 0.15, and 0.17 for F/B ratio, Shannon, Inverse Simpson and Chao1, respectively). CONCLUSION: Suggestive differences observed in women with high and low BD with respect to GM alpha diversity and prevalence of specific GM taxa need to be confirmed in larger studies.

2.
Cancer Causes Control ; 32(4): 347-355, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33484419

RESUMO

PURPOSE: Evidence is mixed on whether cholesterol plays a role in the pathogenesis of glioma. We explored the associations between circulating lipids and glioma risk in three prospective cohorts. METHODS: Using prospective data from the UK Biobank, we examined the associations of total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglycerides (TG) with glioma risk in multivariable (MV)-adjusted Cox proportional hazards models. Within the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS), we carried out a matched, nested case-control study to examine these same associations. RESULTS: In the UK Biobank, 490 gliomas accrued over 2,358,964 person-years. TC was not significantly associated with glioma risk (MV HR = 1.20, 95% CI 0.89-1.61 for highest quartile vs. lowest, p-trend = 0.24). In 4-year lagged analyses (n = 229), higher TC was associated with significantly higher risk of glioma in men (MV HR = 2.26, 95% CI 1.32-3.89, p-trend = 0.002) but not women (MV HR = 1.28, 95% CI 0.61-2.68, p-trend = 0.72); similar findings emerged for HDL-C and, to a lesser extent, LDL-C. In the NHS/HPFS, no significant associations were found between cholesterol and glioma risk. No significant associations were identified for TG. CONCLUSION: In the UK Biobank, higher prediagnostic TC and HDL-C levels were associated with higher risk of glioma in 4-year lagged analyses, but not in non-lagged analyses, in men only. These findings merit further investigation, given that there are few risk factors and no reliable biomarkers of risk identified for glioma.

3.
Cancer Epidemiol Biomarkers Prev ; 30(4): 623-642, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33500318

RESUMO

BACKGROUND: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. METHODS: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. RESULTS: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (P adj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking. CONCLUSIONS: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. IMPACT: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

4.
Int J Cancer ; 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427315

RESUMO

Toxoplasma gondii (T gondii) is a common parasite that shows affinity to neural tissue and may lead to the formation of cysts in the brain. Previous epidemiologic studies have suggested an association between glioma and increased prevalence of T gondii infection, but prospective studies are lacking. Therefore, we examined the association between prediagnostic T gondii antibodies and risk of glioma in two prospective cohorts using a nested case-control study design. Cases and matched controls were selected from the American Cancer Society's Cancer Prevention Study-II Nutrition Cohort (CPSII-NC) (n = 37 cases and 74 controls) and the Norwegian Cancer Registry's Janus Serum Bank (Janus) (n = 323 cases and 323 controls). Blood samples collected prior to diagnosis were analyzed for antibodies to two T gondii surface antigens (p22 and sag-1), with individuals considered seropositive if antibodies to either antigen were detected. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (95% CI) for each cohort. In both cohorts, a suggestive increase in glioma risk was observed among those infected with T gondii (OR: 2.70; 95% CI: 0.96-7.62 for CPSII-NC; OR: 1.32, 95% CI: 0.85-2.07 for Janus), particularly among participants with high antibody titers specific to the sag-1 antigen (CPSII-NC OR: 3.35, 95% CI: 0.99-11.38; Janus OR: 1.79, 95% CI: 1.02-3.14). Our findings provide the first prospective evidence of an association between T gondii infection and risk of glioma. Further studies with larger case numbers are needed to confirm a potential etiologic role for T gondii in glioma.

5.
J Med Imaging (Bellingham) ; 7(5): 055501, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33102623

RESUMO

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively ( p < 0.00007 ). The DL method achieved a mean Dice coefficient of 0.87 on the test cases. Conclusions: This was the first objective comparison of automated and human segmentation using a blinded controlled assessment study. Our DL system learned to outperform its "human teachers" and produced output that was better, on average, than its training data.

6.
Cancer Prev Res (Phila) ; 13(11): 901-910, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32753376

RESUMO

The etiology of triple-negative breast cancers (TNBC) is poorly understood. As many TNBCs develop prior to the initiation of breast cancer screening or at younger ages when the sensitivity of mammography is comparatively low, understanding the etiology of TNBCs is critical for discovering novel prevention approaches for these tumors. Furthermore, the higher incidence rate of estrogen receptor-negative breast cancers, and specifically, of TNBCs, among young African American women (AAW) versus white women is a source of racial disparities in breast cancer mortality. Whereas immune responses to TNBCs have received considerable attention in relation to prognosis and treatment, the concept that dysregulated immune responses may predispose to the development of TNBCs has received limited attention. We present evidence that dysregulated immune responses are critical in the pathogenesis of TNBCs, based on the molecular biology of the cancers and the mechanisms proposed to mediate TNBC risk factors. Furthermore, proposed risk factors for TNBC, especially childbearing without breastfeeding, high parity, and obesity, are more prevalent among AAW than white women. Limited data suggest genetic differences in immune responses by race, which favor a stronger Thr type 2 (Th2) immune response among AAW than white women. Th2 responses contribute to wound-healing processes, which are implicated in the pathogenesis of TNBCs. Accordingly, we review data on the link between immune responses and TNBC risk and consider whether the prevalence of risk factors that result in dysregulated immunity is higher among AAW than white women.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32769047

RESUMO

In order to undertake an epidemiologic study relating levels of parent estrogens (estrone and estradiol) and estrogen metabolites (EMs) to other breast cancer risk factors, we have optimized methods for EM quantification with ultra high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). A two-step approach was adopted; the first step comprised method development and evaluation of the method performance. The second step consisted of applying this method to quantify estrogens in postmenopausal women and determine if the observed patterns are consistent with the existing literature and prior knowledge of estrogen metabolism. First, 1-methylimidazole-2-sulfonyl chloride (MIS) was used to derivatize endogenous estrogens and estrogen metabolites in urine from study participants. Since C18 reversed phase columns have not been able to separate all the structurally related EMs, we used a C18-pentafluorophenyl (PFP) column. The parent estrogens and EMs were baseline resolved with distinct retention times on this C18-PFP column using a 30 min gradient. This method was used to quantify the parent estrogens and 13 EMs in urine samples collected in an initial pilot study involving males as well as pre- and peri-menopausal females to assess a range of EM levels in urine samples and enable comparison to the previous literature for assay evaluation. Detection limits ranged from 1 - 20 pg/mL depending on the EM. We evaluated matrix effects and interference as well as the intra- and inter-batch reproducibility including hydrolysis, extraction, derivatization and LC-MS analysis using charcoal-stripped human urine as a matrix. Methods were then applied to the measurement of estrogens in urine samples from 169 postmenopausal women enrolled in an epidemiological study to examine relationships between breast cancer risk, the intestinal microbiome, and urinary EMs. The results from our cohort are comparable to previous reports on urinary EMs in postmenopausal women and enabled thorough evaluation of the method.

8.
BMC Cancer ; 20(1): 447, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32429869

RESUMO

BACKGROUND: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. METHODS: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). RESULTS: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR = 1.027, p = 0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR = 1.011, p < 0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p = 0.010 t-test), but tumor size was not correlated with female overall survival (p = 0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p = 0.004, F p = 0.001, t-test). CONCLUSION: Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

9.
Eur J Nutr ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32388734

RESUMO

PURPOSE: Reduced cognitive function associated with aging has gained increasing attention as the US population ages. Magnesium plays a critical role in vitamin D biosynthesis and metabolism; and deficiencies in magnesium and vitamin D show associations with poor cognition. However, no study has examined their interaction. This study aimed to evaluate the associations of magnesium intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, indicating vitamin D status, with cognition, and interaction between these nutrients in older adults. METHODS: Based on the National Health and Nutrition Survey (NHANES) 2011-2014, the study included 2466 participants aged ≥ 60 years who completed the Digit Symbol Substitution Test (DSST) and had data available on serum 25(OH)D and magnesium intake. Cognitive impairment was defined as a DSST score lower than the lowest quartile. Serum 25(OH)D concentrations were measured by HPLC-tandem mass spectrometry. RESULTS: Higher total magnesium intake was independently associated with higher DSST scores (highest quartile vs lowest: ß = 4.34, 95% CI 1.14-7.54). The association of total magnesium intake with high DSST score was primarily observed among women, non-Hispanic whites, physically active participants and those with sufficient vitamin D status, although the interactions were not significant. The odds of cognitive impairment was reduced with increasing intake of total magnesium (p trend < 0.01) and higher level of serum 25(OH)D (p trend = 0.05). CONCLUSIONS: Findings suggest that high magnesium intake alone may improve cognitive function in older adults, and the association may be stronger among subjects with sufficient vitamin D status. Further studies are needed to confirm these findings.

10.
Eur J Cancer ; 129: 123-131, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32151942

RESUMO

BACKGROUND: Coffee and tea have been hypothesised to reduce the risk of some cancers; however, their impact on glioma is less well studied. METHODS: We examined associations between self-reported intake of tea and coffee in relation to glioma risk in the UK Biobank. We identified 487 incident glioma cases among 379,259 participants. Hazard ratios (HR) and 95% confidence intervals (CI) for glioma according to caffeinated beverage consumption were calculated using Cox proportional hazards regression with adjustment for age, gender, race and education; daily cups of tea or coffee were included in models considering the other beverage. RESULTS: Consuming 4 or more cups of tea was associated with reduced risk of glioma when compared to no tea consumption (HR = 0.69; 95% CI, 0.51-0.94). A significant inverse association was observed for glioblastoma (HR = 0.93 per 1 cup/d increment; 95% CI, 0.89-0.98) and among males for all gliomas combined (HR = 0.95 per 1 cup/d increment; 95% CI, 0.90-1.00). A suggestive inverse association was also observed with greater consumption of coffee (HR = 0.71; 95% CI, 0.49-1.05 for >4 versus 0 cups/d). Results were not materially changed with further adjustment for smoking, alcohol and body mass index. Associations were similar in 2-year and 3-year lagged analyses. CONCLUSIONS: In this prospective study, we found a significant inverse association between tea consumption and the risk of developing glioma, and a suggestive inverse association for the consumption of coffee. Further investigation on the possible preventive role of caffeine in glioma is warranted.


Assuntos
Neoplasias Encefálicas/epidemiologia , Café , Glioma/epidemiologia , Inquéritos Nutricionais/estatística & dados numéricos , Chá , Bancos de Espécimes Biológicos/estatística & dados numéricos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/prevenção & controle , Comportamento Alimentar , Feminino , Seguimentos , Glioma/patologia , Glioma/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Fatores de Risco , Autorrelato/estatística & dados numéricos , Fatores Sexuais , Reino Unido/epidemiologia
11.
Breast Cancer Res Treat ; 180(1): 1-19, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897901

RESUMO

PURPOSE: Epidemiological evidence on the risk factors for uterine/endometrial cancer in breast cancer (BCa) survivors is limited and inconsistent. Therefore, we critically reviewed and summarized available evidence related to the risk factors for uterine/endometrial cancer in BCa survivors. METHODS: We conducted a literature search through PubMed, Web of Science Core Collection/Cited Reference Search, as well as through manual searches of the bibliographies of the articles identified in electronic searches. We included in this review studies that were published up to November 30, 2018 that were accessible in full-text format and were published in English. RESULTS: Of the 27 eligible studies, 96% had > 700 participants, 74% were prospective cohorts, 70% originated outside of the US, 44% reported as having pre-/postmenopausal women, and 26% reported having racially heterogeneous populations. Risk factors positively associated with uterine/endometrial cancer risk among BCa survivors included age at BCa diagnosis > 50 years, African American race, greater BMI/weight gain, and Tamoxifen treatment. For other lifestyle, reproductive and clinical factors, associations were either not significant (parity) or inconsistent (HRT use, menopausal status, smoking status) or had limited evidence (alcohol intake, family history of cancer, age at first birth, oral contraceptive use, age at menopause, comorbidities). CONCLUSION: We identified several methodological concerns and limitations across epidemiological studies on potential risk factors for uterine/endometrial cancer in BCa survivors, including lack of details on uterine/endometrial cancer case ascertainment, varying and imprecise definitions of important covariates, insufficient adjustment for potential confounders, and small numbers of uterine/endometrial cancer cases in the overall as well as stratified analyses. Based on the available evidence, older age and higher body weight measures appear to be a shared risk factor for uterine/endometrial cancer in the general population as well as in BCa survivors. In addition, there is suggestive evidence that African American BCa survivors have a higher risk of uterine/endometrial cancer as compared to their White counterparts. There is also evidence that Tamoxifen contributes to uterine/endometrial cancer in BCa survivors. Given limitations of existing studies, more thorough investigation of these associations is warranted to identify additional preventive strategies needed for BCa survivors to reduce uterine/endometrial cancer risk and improve overall survival.


Assuntos
Neoplasias da Mama/epidemiologia , Sobreviventes de Câncer , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias Uterinas/epidemiologia , Neoplasias Uterinas/etiologia , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Feminino , Humanos , Vigilância em Saúde Pública , Medição de Risco , Fatores de Risco
12.
Int J Cancer ; 146(3): 739-748, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30963577

RESUMO

Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with ≥40% AA (AFR≥0.4 ), and ≥15% NAA (AMR≥0.15 ), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 × 10-4 ; 11p11.12, p = 7.0 × 10-4 ) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR≥0.4 . In addition, we identified a peak at rs1620291 (p = 4.36 × 10-6 ) in 7q21.3. Among AMR≥0.15 , we found an association between increased EA in one region (12q24.21, p = 8.38 × 10-4 ), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 × 10-4 ). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies.


Assuntos
Afro-Americanos/genética , Predisposição Genética para Doença/genética , Glioma/etiologia , Glioma/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Estudos de Associação Genética/métodos , Loci Gênicos/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Hispano-Americanos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Risco
13.
Sci Rep ; 9(1): 19673, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31873162

RESUMO

In cancer patients, a high pre-treatment neutrophil-to-lymphocyte ratio (NLR) is associated with poorer survival outcomes. Significant variation in the magnitude of this association has been observed between studies, but sources of this variation are poorly understood. Here, we explore differences in the prognostic potential of NLR between patient subgroups stratified by demographic and clinical characteristics using a retrospective cohort of 5,363 patients treated at Moffitt Cancer Center (Tampa, FL). We identify patients for whom NLR has maximum prognostic potential via adjusted hazard ratios (HRs) calculated using multivariable Cox proportional hazards models and area under the curve analysis. NLR demonstrates stronger associations (HRs > 2) with survival among African-American patients, patients receiving radiation therapy, stage IV patients, and melanoma patients when compared with the overall study population (HR = 1.58). Sensitivity and specificity of NLR as a prognostic marker are also higher in these patient subgroups, and increase further with combinations of multiple "high-risk" demographic or clinical characteristics. In summary, NLR may have greater prognostic value in patients with certain demographic and clinical features. Future prospective studies could validate this hypothesis, after further characterization of populations in which NLR has maximum prognostic potential and the identification of meaningful thresholds for risk stratification.


Assuntos
Linfócitos , Neoplasias/sangue , Neutrófilos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Inflamação/sangue , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Neutrófilos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Estudos Retrospectivos
14.
Eur J Epidemiol ; 34(11): 997-1011, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31559554

RESUMO

Background Statins have previously been shown to have protective effects for other cancers, but no prospective studies of statin use and glioma have been conducted. Methods We evaluated the association between statin use and risk of glioma in the female Nurses' Health Study (NHS, n = 114,419) and Nurses' Health Study II (NHSII, n = 115,813) and the male Health Professionals Follow-up Study (HPFS, n = 50,223). Glioma cases were confirmed by medical record review. Age and multivariable-adjusted hazard ratios of glioma by statin use were estimated using Cox proportional hazards models. Results In 4,430,700 person-years of follow-up, we confirmed 483 incident cases of glioma. Compared with never-users, ever statin use was associated with borderline increased risk of glioma in the combined cohorts (age-adjusted HR = 1.23, 95% CI 0.99-1.54), as was longer duration of statin use (HR = 1.48, 95% CI 1.08-2.03 comparing > 8 years of use to never use, p-trend = 0.01). We also observed a significant inverse association between hyperlipidemia and glioma in multivariable models (HR = 0.74, 95% CI 0.59-0.93 in combined cohorts), which was attenuated in lagged analyses. Compared to never use, in multivariable-adjusted models, ever statin use (HR = 1.43, 95% CI 1.10-1.86) and statin use duration (HR = 1.72, 95% CI 1.21-2.45, for > 8 years of use, p-trend = 0.003) were each significantly associated with increased glioma risk. Conclusion In contrast to case-control studies reporting inverse associations, we found borderline increased risk of glioma with statin use. Results were strengthened after adjustment for cardiovascular risk factors due to an unexpected inverse association between hyperlipidemia and glioma risk. Further studies of statin use, hyperlipidemia, and glioma risk are warranted.


Assuntos
Glioma/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , Adulto , Idoso , Índice de Massa Corporal , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hiperlipidemias/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fumar/epidemiologia , Estados Unidos/epidemiologia
15.
Ann Epidemiol ; 38: 11-21.e6, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31481293

RESUMO

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation with established prognostic value in patients with cancer. Although high NLR is associated with poorer clinical outcomes, factors that influence the magnitude of NLR independently of disease are poorly understood. METHODS: We identified 48,023 adults who participated in the National Health and Nutrition Examination Survey (1999-2016). Demographic, socioeconomic, and lifestyle factors associated with the magnitude of NLR after adjusting for comorbidities including heart disease, cancer, diabetes, and hypertension, and medications including aspirin, were identified. Effect modification by comorbidity status and demographics was explored. RESULTS: Female gender, age less than 60 years, and non-Hispanic black race/ethnicity were associated with lower NLR. Marital statuses of widowed, separated, or never married demonstrated increased NLR as compared with those who were currently married. Never-smoking and moderate alcohol consumption were associated with lower NLR. Participation in physical activity was associated with decreased NLR after adjustment for potential confounders, primarily among non-Hispanic whites. CONCLUSIONS: Multiple demographic and lifestyle factors are independently associated with NLR. Sex, age, race, marital status, body mass index, physical activity, smoking history, and alcohol consumption should all be routinely collected and adjusted for to improve the accuracy of assessment of the prognostic power of NLR.


Assuntos
Inflamação/sangue , Estilo de Vida , Linfócitos , Neutrófilos , Fatores Socioeconômicos , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Biomarcadores , Índice de Massa Corporal , Estudos Transversais , Exercício Físico , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fumar
16.
Sci Rep ; 9(1): 10861, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350461

RESUMO

Methylmercury (MeHg) is an environmental neurotoxin with human exposure mainly from dietary intake of contaminated fish. Exposure to MeHg has been implicated in neurological damage, but research on its role in cancers, specifically glioma, is limited. In a glioma case-control study, we examined associations between toenail mercury (Hg) and glioma risk. We also examined genetic polymorphisms in 13 genes related to MeHg metabolism for association with glioma risk; genetic associations were also studied in the UK Biobank cohort. Median toenail Hg in cases and controls, respectively, was 0.066 µg/g and 0.069 µg/g (interquartile range (IQR): 0.032-0.161 and 0.031-0.150 µg/g). Toenail Hg was not found to be significantly associated with glioma risk (Odds Ratio: 1.02; 95% Confidence Interval: 0.91, 1.14; p = 0.70 in analysis for ordinal trend with increasing quartile of toenail MeHg). No genetic variant was statistically significant in both of the studies; one variant, rs11859163 (MMP2) had a combined p-value of 0.02 though it was no longer significant after adjustment for multiple testing (Bonferroni corrected p = 1). This study does not support the hypothesis that exposure to MeHg plays a role in the development of glioma at levels of exposure found in this study population.


Assuntos
Neoplasias Encefálicas/epidemiologia , Glioma/epidemiologia , Metaloproteinase 2 da Matriz/genética , Mercúrio/análise , Compostos de Metilmercúrio/metabolismo , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Exposição Dietética , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Compostos de Metilmercúrio/análise , Pessoa de Meia-Idade , Unhas/química , Estudos Prospectivos , Fatores de Risco , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
17.
Am J Clin Oncol ; 42(8): 655-661, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31343422

RESUMO

Although glioblastoma (GBM) is a fatal primary brain cancer with short median survival of 15 months, a small number of patients survive >5 years after diagnosis; they are known as extreme survivors (ES). Because of their rarity, very little is known about what differentiates these outliers from other patients with GBM. For the purpose of identifying unknown drivers of extreme survivorship in GBM, the ENDURES consortium (ENvironmental Dynamics Underlying Responsive Extreme Survivors of GBM) was developed. This consortium is a multicenter collaborative network of investigators focused on the integration of multiple types of clinical data and the creation of patient-specific models of tumor growth informed by radiographic and histologic parameters. Leveraging our combined resources, the goals of the ENDURES consortium are 2-fold: (1) to build a curated, searchable, multilayered repository housing clinical and outcome data on a large cohort of ES patients with GBM; and (2) to leverage the ENDURES repository for new insights into tumor behavior and novel targets for prolonging survival for all patients with GBM. In this article, the authors review the available literature and discuss what is already known about ES. The authors then describe the creation of their consortium and some preliminary results.


Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Sistema de Registros , Idoso , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/patologia , Humanos , Gestão da Informação , Comunicação Interdisciplinar , Colaboração Intersetorial , Masculino , Pessoa de Meia-Idade , Sistema de Registros/normas , Taxa de Sobrevida
18.
J Palliat Med ; 22(10): 1202-1207, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31081711

RESUMO

Background: Glioma is a devastating primary tumor of the central nervous system with difficult-to-manage symptoms. Cannabis products have been postulated to potentially benefit glioma patients. Recent state legalization allowed investigators an opportunity to study glioma patients' adoption of medical marijuana (MM). Objective: Our goals were to: (1) determine the prevalence of marijuana use, both through physician recommendation and self-medication, and (2) evaluate its perceived risks and benefits in glioma patients. Design: Self-report data were collected and descriptive analyses were conducted. Setting/Subjects: Participants were adult, English-speaking patients undergoing treatment for primary non-recurrent malignant glioma in neuro-oncology clinics at an NCI-designated Comprehensive Cancer Center. Measurements: The survey on MM was adapted from previous research and included questions on knowledge and attitudes toward MM; use, frequency, type, and sourcing of MM; and reasons for use of MM and perceived symptom relief among users. Results: A total of 73 patients were surveyed. The majority of participants were aware that MM was legal in the state, and most reported learning of this through the media. Over 70% of participants reported having considered using MM, and a third reported using marijuana products after their diagnosis. Most received recommendations from friends/family rather than a medical provider, and only half of the users had obtained a physician's recommendation. Users generally reported benefits. Conclusions: With the increasing national conversation that accompanies legalization, glioma patients are pursuing marijuana for the treatment for their symptoms. More research and education is needed to bring health care providers into the conversation.


Assuntos
Neoplasias Encefálicas/terapia , Glioma/terapia , Maconha Medicinal/uso terapêutico , Cuidados Paliativos , Adulto , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer , Feminino , Florida , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Padrões de Prática Médica/estatística & dados numéricos , Automedicação , Autorrelato , Inquéritos e Questionários
19.
Tomography ; 5(1): 135-144, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30854451

RESUMO

Standard-of-care multiparameter magnetic resonance imaging (MRI) scans of the brain were used to objectively subdivide glioblastoma multiforme (GBM) tumors into regions that correspond to variations in blood flow, interstitial edema, and cellular density. We hypothesized that the distribution of these distinct tumor ecological "habitats" at the time of presentation will impact the course of the disease. We retrospectively analyzed initial MRI scans in 2 groups of patients diagnosed with GBM, a long-term survival group comprising subjects who survived >36 month postdiagnosis, and a short-term survival group comprising subjects who survived ≤19 month postdiagnosis. The single-institution discovery cohort contained 22 subjects in each group, while the multi-institution validation cohort contained 15 subjects per group. MRI voxel intensities were calibrated, and tumor voxels clustered on contrast-enhanced T1-weighted and fluid-attenuated inversion-recovery (FLAIR) images into 6 distinct "habitats" based on low- to medium- to high-contrast enhancement and low-high signal on FLAIR scans. Habitat 6 (high signal on calibrated contrast-enhanced T1-weighted and FLAIR sequences) comprised a significantly higher volume fraction of tumors in the long-term survival group (discovery cohort, 35% ± 6.5%; validation cohort, 34% ± 4.8%) compared with tumors in the short-term survival group (discovery cohort, 17% ± 4.5%, P < .03; validation cohort, 16 ± 4.0%, P < .007). Of the 6 distinct MRI-defined habitats, the fractional tumor volume of habitat 6 at diagnosis was significantly predictive of long- or short-term survival. We discuss a possible mechanistic basis for this association and implications for habitat-driven adaptive therapy of GBM.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioblastoma/diagnóstico por imagem , Adulto , Idoso , Neoplasias Encefálicas/patologia , Meios de Contraste , Feminino , Glioblastoma/patologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Adulto Jovem
20.
Semin Cancer Biol ; 56: 135-148, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-29294371

RESUMO

Gliomas are a highly heterogeneous tumor, refractory to treatment and the most frequently diagnosed primary brain tumor. Although the current WHO grading system (2016) demonstrates promise towards identifying novel treatment modalities and better prediction of prognosis over time, to date, existing targeted and mono therapy approaches have failed to elicit a robust impact on disease progression and patient survival. It is possible that tumor heterogeneity as well as specifically targeted agents fail because redundant molecular pathways in the tumor make it refractory to such approaches. Additionally, the underlying metabolic pathology, which is significantly altered during neoplastic transformation and tumor progression, is unaccounted for. With several molecular and metabolic pathways implicated in the carcinogenesis of CNS tumors, including glioma, we postulate that a systemic, broad spectrum approach to produce robust targeting of relevant and multiple molecular and metabolic regulation of growth and survival pathways, critical to the modulation of hallmarks of carcinogenesis, without clinically limiting toxicity, may provide a more sustained impact on clinical outcomes compared to the modalities of treatment evaluated to date. The objective of this review is to examine the emerging hallmark of reprogramming energy metabolism of the tumor cells and the tumor microenvironment during carcinogenesis, and to provide a rationale for exploiting this hallmark and its biological capabilities as a target for secondary chemoprevention and treatment of glioma. This review will primarily focus on interventions to induce ketosis to target the glycolytic phenotype of many cancers, with specific application to secondary chemoprevention of low grade glioma- to halt the progression of lower grade tumors to more aggressive subtypes, as evidenced by reduction in validated intermediate endpoints of disease progression including clinical symptoms.


Assuntos
Antineoplásicos/uso terapêutico , Metabolismo Energético/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Animais , Antineoplásicos/farmacologia , Transformação Celular Neoplásica , Dieta Cetogênica , Suplementos Nutricionais , Gerenciamento Clínico , Progressão da Doença , Glioma/tratamento farmacológico , Glioma/etiologia , Glioma/metabolismo , Glioma/patologia , Glucose/metabolismo , Glicólise , Humanos , Cetose , Terapia de Alvo Molecular , Neoplasias/etiologia , Neoplasias/patologia , Estresse Oxidativo , Resultado do Tratamento
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