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1.
Anticancer Res ; 40(1): 27-34, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892550

RESUMO

BACKGROUND/AIM: Even though prostate cancer (PCa) has good prognosis, there is a discrepancy in the risk among ethnic groups, with high morbidity in African American men. Single nucleotide polymorphisms (SNPs) in interleukin 10 (IL-10) have been associated with inflammation and cancer risk. We investigated the association of five SNPs in the IL-10 promoter with clinical features such as Gleason score and smoking. MATERIALS AND METHODS: A total of 413 DNA samples were obtained from a nested case-control study of African American males who were genotyped for 5 SNPs utilizing pyrosequencing. Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. RESULTS: rs12122923 and rs1800871 were associated with PCa risk. Smoking was also found to increase the risk of PCa by 1.6-fold. rs1800893 was found to be associated with lower grades for prostate cancer. CONCLUSION: IL-10 promoter polymorphisms might be a risk factor for PCa development in smoking subjects and PCa progression.


Assuntos
Afro-Americanos/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias da Próstata/etiologia , Fumar/efeitos adversos , Idoso , Alelos , Biomarcadores , Estudos de Casos e Controles , Suscetibilidade a Doenças , Genótipo , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/patologia , Medição de Risco , Fatores de Risco
2.
Genet Med ; 21(12): 2676-2680, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31160752

RESUMO

PURPOSE: Minorities are often underrepresented in clinical cancer research yet the frequency of reporting of race in genomic sequencing studies of cancer is unknown. This scoping review determines the rate at which race is reported as a demographic variable, the factors associated with reporting of race, and the participation rates of minority populations. METHODS: PubMed was systematically searched from 1 January 2010 through 15 November 2018 and 11,014 studies were assessed for eligibility. Publications reporting genome or exome sequencing data for patients with one of the ten most common cancers in the United States were included. RESULTS: A total of 231 publications containing sequencing data from 15,721 unique patients met inclusion criteria. Race was reported in 37% of studies compared with 84% of studies reporting age and 85% reporting gender. Reporting of race was associated with cohort size, sequencing method, familial cancer, cancers with disparities, and reporting of age and gender. Minority populations were significantly underpowered to detect recurrent pathogenic variants in most cancers. CONCLUSION: Race is underreported as a demographic variable in genomic sequencing studies of cancer. Substantially increased efforts are needed to sequence patients from underrepresented populations to reduce health disparities in patients of non-European ancestry.

3.
J Community Genet ; 10(4): 471-480, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30877487

RESUMO

This study evaluated factors associated with willingness to provide biospecimens for cancer genetic research among African American cancer survivors. A total of 200 African American adults diagnosed with breast, colon, and/or prostate cancers completed a self-administered survey. Family history information, beliefs about cancer research, cancer genetics and disparities knowledge, willingness to provide a biospecimen, and demographics were obtained. Chi-square, independent samples t tests, and logistic regression analyses were performed. Overall, 79% of this sample was willing to provide a biospecimen for cancer genetics research. Independent associations of willingness to provide a biospecimen existed among demographics (males (p = 0.041)), those who believed in the importance of genetic causes of cancer (p < 0.001), individuals who believe it is important to participate in genetics research (p < 0.001), and those who indicated they would participate in genetics research to help future generations (p = 0.026). Overall, 12.5-56% of participants demonstrated some level of genetics and cancer disparities. This study identified factors that may be incorporated into future research interventions to engage the African American cancer population in cancer genetics biobanking research.

4.
Int J Part Ther ; 5(1): 103-113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30505881

RESUMO

Radiogenomics is the study of genomic factors that are associated with response to radiation therapy. In recent years, progress has been made toward identifying genetic risk factors linked with late radiation-induced adverse effects. These advances have been underpinned by the establishment of an international Radiogenomics Consortium with collaborative studies that expand cohort sizes to increase statistical power and efforts to improve methodologic approaches for radiogenomic research. Published studies have predominantly reported the results of research involving patients treated with photons using external beam radiation therapy. These studies demonstrate our ability to pool international cohorts to identify common single nucleotide polymorphisms associated with risk for developing normal tissue toxicities. Progress has also been achieved toward the discovery of genetic variants associated with radiation therapy-related subsequent malignancies. With the increasing use of charged particle therapy (CPT), there is a need to establish cohorts for patients treated with these advanced technology forms of radiation therapy and to create biorepositories with linked clinical data. While some genetic variants are likely to impact toxicity and second malignancy risks for both photons and charged particles, it is plausible that others may be specific to the radiation modality due to differences in their biological effects, including the complexity of DNA damage produced. In recognition that the formation of patient cohorts treated with CPT for radiogenomic studies is a high priority, efforts are underway to establish collaborations involving institutions treating cancer patients with protons and/or carbon ions as well as consortia, including the Proton Collaborative Group, the Particle Therapy Cooperative Group, and the Pediatric Proton Consortium Registry. These important radiogenomic CPT initiatives need to be expanded internationally to build on experience gained from the Radiogenomics Consortium and epidemiologists investigating normal tissue toxicities and second cancer risk.

6.
Oncotarget ; 9(32): 22693-22702, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29854308

RESUMO

T-cell lymphoma (TCL) is an uncommon and aggressive form of human cancer. Lymphoma is the most common hematopoietic tumor in canines (companion animals), with TCL representing approximately 30% of diagnoses. Collectively, the canine is an appealing model for cancer research given the spontaneous occurrence of cancer, intact immune system, and phytogenetic proximity to humans. We sought to establish mutational congruence of the canine with known human TCL mutations in order to identify potential actionable oncogenic pathways. Following pathologic confirmation, DNA was sequenced in 16 canine TCL (cTCL) cases using a custom Human Cancer Hotspot Panel of 68 genes commonly mutated in human TCL. Sequencing identified 4,527,638 total reads with average length of 229 bases containing 346 unique variants and 1,474 total variants; each sample had an average of 92 variants. Among these, there were 258 germline and 32 somatic variants. Among the 32 somatic variants there were 8 missense variants, 1 splice junction variant and the remaining were intron or synonymous variants. A frequency of 4 somatic mutations per sample were noted with >7 mutations detected in MET, KDR, STK11 and BRAF. Expression of these associated proteins were also detected via Western blot analyses. In addition, Sanger sequencing confirmed three variants of high quality (MYC, MET, and TP53 missense mutation). Taken together, the mutational spectrum and protein analyses showed mutations in signaling pathways similar to human TCL and also identified novel mutations that may serve as drug targets as well as potential biomarkers.

7.
Ann Diagn Pathol ; 34: 170-174, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29715580

RESUMO

OBJECTIVES: Proteins p27 and c-Myc are both key players in the cell cycle. While p27, a tumor suppressor, inhibits progression from G1 to S phase, c-Myc, a proto-oncogene, plays a key role in cell cycle regulation and apoptosis. The objective of our study was to determine the association between expression of c-Myc and the loss of p27 by immunohistochemistry (IHC) in the four major subtypes of breast cancer (BC) (Luminal A, Luminal B, HER2, and Triple Negative) and with other clinicopathological factors in a population of 202 African-American (AA) women. MATERIALS AND METHODS: Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 AA women. Five micrometer sections were stained with a mouse monoclonal antibody against p27 and a rabbit monoclonal antibody against c-Myc. The sections were evaluated for intensity of nuclear reactivity (1-3) and percentage of reactive cells; an H-score was derived from the product of these measurements. RESULTS: Loss of p27 expression and c-Myc overexpression showed statistical significance with ER negative (p < 0.0001), PR negative (p < 0.0001), triple negative (TN) (p < 0.0001), grade 3 (p = 0.038), and overall survival (p = 0.047). There was no statistical significant association between c-Myc expression/p27 loss and luminal A/B and Her2 overexpressing subtypes. CONCLUSION: In our study, a statistically significant association between c-Myc expression and p27 loss and the triple negative breast cancers (TNBC) was found in AA women. A recent study found that constitutive c-Myc expression is associated with inactivation of the axin 1 tumor suppressor gene. p27 inhibits cyclin dependent kinase2/cyclin A/E complex formation. Axin 1 and CDK inhibitors may represent possible therapeutic targets for TNBC.


Assuntos
Carcinoma Ductal de Mama/metabolismo , Ciclinas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Anticorpos Monoclonais , Carcinoma Ductal de Mama/patologia , Ciclo Celular , Feminino , Humanos , Camundongos , Pessoa de Meia-Idade , Coelhos , Análise Serial de Tecidos , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
8.
Cancer Genomics Proteomics ; 15(3): 185-191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29695400

RESUMO

BACKGROUND/AIM: Prostate cancer is the most common malignancy in US males. African American men have higher incidence and mortality rates than European Americans. Five single nucleotide polymorphisms are associated with PCa. We hypothesized haplotypes inferred from these SNPs are also associated with PCa. PATIENTS AND METHODS: We genotyped SNPs in a case-control admixture mapping study. SNP haplotypes inferred for 157 PCa cases and 150 controls were used in the regression analysis. RESULTS: We found an association between "GTCCC", "ATTCT", and "ACCCC" haplotypes and PCa after ancestry adjustment (OR=3.62, 95%CI=1.42-9.21, p=0.0070; OR=7.89, 95%CI=2.36-26.31, p=0.0008; OR=4.34, 95%CI=1.75-10.78, p=0.0016). The rs615382 variant disrupts the recombination signal binding protein with immunoglobulin kappa J binding site in Rac GTPase activating protein 1 (RACGAP1). CONCLUSION: Disruption of notch 1 mediated-repression of RACGAP1 may contribute to PCa in African Americans.


Assuntos
Afro-Americanos/genética , Mapeamento Cromossômico/métodos , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/genética , Receptor Notch1/genética , Adenocarcinoma/genética , Adenocarcinoma/patologia , Idoso , Estudos de Casos e Controles , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Próstata/patologia
9.
Pathol Res Pract ; 214(5): 673-678, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29653745

RESUMO

INTRODUCTION: PTEN is a tumor suppressor gene that inhibits cell proliferation by inhibiting the phosphoinositide 3-kinase (PI3 K) signaling pathway. The significance of PTEN mutations resulting in variable PTEN expression and their impact on prognosis of breast cancer is not well established. The objective of our study was to correlate the immunohistochemical expression of PTEN in the four major subtypes of breast carcinoma (Luminal A, Luminal B, HER2 positive, and Triple Negative) in a population of 202 African-American (AA) females with other clinicopathological factors. MATERIALS AND METHODS: Tissue microarrays (TMAs) were constructed from FFPE tumor blocks from primary ductal breast carcinomas in 202 African-American females. Five micrometer sections were stained with a mouse monoclonal antibody against PTEN. The sections were evaluated for the intensity of cytoplasmic and nuclear reactivity. Bivariate analysis was done via χ2 analysis and survivability data was calculated via the generation of Kaplan-Meier curves (SPSS v19). RESULTS: Loss of PTEN expression was associated with ER negative (p = 0.021), PR negative (p = 0.024) and triple negative (p = 0.0024) breast ductal cancers. It was marginally associated with distant metastasis (p = 0.074). There was no association between PTEN loss and recurrence-free survival or overall survival. CONCLUSION: In our study, a statistically significant association between PTEN loss and the triple negative breast cancers (TNBC) was found in AA women. PTEN inhibits PI3 K resulting in decreased activation of downstream effector, mammalian target of rapamycin (mTOR). Loss of PTEN results in cell proliferation through activation of mTOR. Targeted therapy with mTOR inhibitors might be useful in the treatment of TNBC.


Assuntos
Carcinoma Ductal de Mama/patologia , PTEN Fosfo-Hidrolase/genética , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Afro-Americanos , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
10.
J Health Care Poor Underserved ; 29(1): 509-529, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29503315

RESUMO

The aim of this study was to determine the impact of race and socioeconomic status on breast tumor clinicopathological features and survival outcomes. This study used breast cancer data from the Washington D.C. Cancer Registry (2000- 2010). Logistic regression and survival analysis assessed the association between race, socioeconomic (SES) variables, clinicopathological variables, recurrence-free survival and overall survival. African American (AA) breast cancer patients had an increased risk for stage III, ER-, and PR-breast cancer compared with White and Hispanic breast cancer patients. Additionally, D.C. geographical areas of lower socioeconomic status had higher incidences of stage III and stage IV breast cancer. A nested analysis demonstrated that AAs with higher median incomes compared with AAs with lower incomes revealed no differences for clinicopathological variables, nor were differences found between overall and recurrence-free survival. This study suggests that the biology of breast cancer in AAs could be driving breast cancer disparities.


Assuntos
Afro-Americanos/estatística & dados numéricos , Neoplasias da Mama/etnologia , Neoplasias da Mama/terapia , Classe Social , Idoso , Neoplasias da Mama/patologia , District of Columbia/epidemiologia , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Hispano-Americanos/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Sistema de Registros , Análise de Sobrevida , Resultado do Tratamento
11.
BMC Cancer ; 18(1): 274, 2018 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-29523126

RESUMO

BACKGROUND: MYC overexpression is associated with poor prognosis in breast tumors (BCa). The objective of this study was to determine the prevalence of MYC amplification and associated markers in BCa tumors from African American (AA) women and determine the associations between MYC amplification and clinico-pathological characteristics. METHODS: We analyzed 70 cases of well characterized archival breast ductal carcinoma specimens from AA women for MYC oncogene amplification. Utilizing immune histochemical analysis estrogen receptor (ER), progesterone receptor (PR), and (HER2/neu), were assessed. Cases were Luminal A (ER or PR+, Ki-67 < 14%), Luminal B (ER or PR+, Ki-67 = > 14% or ER or PR+ HER2+), HER2 (ER-, PR-, HER2+), and Triple Negative (ER-, PR-, HER2-) with basal-like phenotype. The relationship between MYC amplification and prognostic clinico-pathological characteristics was determined using chi square and logistic regression modeling. RESULTS: Sixty-five (97%) of the tumors showed MYC gene amplification (MYC: CEP8 > 1). Statistically significant associations were found between MYC amplification and HER2-amplified BCa, and Luminal B subtypes of BCa (p < 0.0001), stage (p < 0.001), metastasis (p < 0.001), and positive lymph node status (p = 0.039). MYC amplification was associated with HER2 status (p = 0.01) and tumor size (p = 0.01). High MYC amplification was seen in grade III carcinomas (MYC: CEP8 = 2.42), pre-menopausal women (MYC: CEP8 = 2.49), PR-negative status (MYC: CEP8 = 2.42), and ER-positive status (MYC: CEP8 = 2.4). CONCLUSIONS: HER2 positive BCas in AA women are likely to exhibit MYC amplification. High amplification ratios suggest that MYC drives HER2 amplification, especially in HER2 positive, Luminal B, and subtypes of BCa.


Assuntos
Afro-Americanos/genética , Neoplasias da Mama/genética , Amplificação de Genes , Proteínas Proto-Oncogênicas c-myc/genética , Receptor ErbB-2/genética , Receptores Estrogênicos/genética , Receptores de Progesterona/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/metabolismo , Estudos Retrospectivos
12.
Med Acupunct ; 29(5): 313-321, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-29067142

RESUMO

Objective: The hot flash is a common vasomotor disorder that causes distress in menopausal women and that can be debilitating in men with prostate cancer who are treated with androgen deprivation therapy (ADT). The utility of auricular electroacupuncture (AEA) was tested exclusively for a small cohort of men with ADT-induced vasomotor symptoms while the men underwent a course of curative radiotherapy. Materials and Methods: Prior to and during radiotherapy treatment, men with vasomotor symptoms were given repeated questionnaires regarding severity and frequency of hot flashes, quality of life (QoL), and sleep over a 6-week span of an AEA protocol. Each subject's heart rate variability (HRV) was obtained repeatedly every week in an ambulatory setting with a BlueCardio device (BlueCardio, Miami, FL). The AEA intervention was given with a Neurova device (Nunka Corporation, CM Wellness Clinic, Pompano Beach, FL) that used three needles at Master points Sympathetic, Shen Men, and Point Zero, which were located precisely with a bipolar point finder. Intermittent microcurrent stimulation was given every other week for 96 hours, using a cyclic programmed output of 2 hours on and 2 hours off. Results: Of 10 men completing the 6-week protocol, all responded with significantly lower frequency, duration, and severity of vasomotor symptoms; QoL and sleep scores improved significantly. The HRV analysis showed significantly lower low-frequency/high-frequency power ratios in each individual, compared to baseline, that were consistent with the subjective responses. Conclusions: Vasomotor disturbance, caused by gender hormone withdrawal-either naturally or in patients treated with ADT, as in this study-is a well-defined neurophysiologic condition. This disorder is a constellation of findings that reflect autonomic disturbances of excessive sympathetic and reduced parasympathetic activity. AEA intervention with the Neurova device is simple to administer, is well-tolerated, and appears to be effective for restoring autonomic balance. Further evaluation of AEA for vasomotor disturbances could provide more insight into the mechanisms of AEA neuromodulation and potentially lead to approaches for treating not only these symptoms but also other neurologic conditions with components of autonomic disturbances.

13.
In Vivo ; 31(4): 661-668, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28652435

RESUMO

BACKGROUND/AIMS: Breast cancer (BCa) prognostication is a vital element for providing effective treatment for patients with BCa. Studies suggest that ethnicity plays a greater role in the incidence and poor prognosis of BCa in younger women than in their older counterparts. Therefore, the goal of this study was to assess the association between age and ethnicity on the overall final prognosis. MATERIALS AND METHODS: Nottingham Prognostic Index (NPI) was used to analyze BCa prognosis using Howard University Cancer Center Tumor Registry and the National Cancer Institute's Surveillance, Epidemiology, and End Results BCa datasets. Patients were grouped according to their predicted prognosis based on NPI scheme. RESULTS: There was no correlation between the younger patients compared to their older counterparts for any of the prognostic clusters. The significance of ethnicity in poorer prognosis for younger age is not conclusive either. CONCLUSION: An extended prognostic tool/system needs to be evaluated for its usefulness in a clinical practice environment.


Assuntos
Fatores Etários , Neoplasias da Mama/epidemiologia , Grupos Étnicos , Prognóstico , Adulto , Afro-Americanos , Idoso , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
14.
Ethn Dis ; 27(2): 169-178, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28439188

RESUMO

BACKGROUND: Variants of unknown significance (VUSs) have been identified in BRCA1 and BRCA2 and account for the majority of all identified sequence alterations. Notably, VUSs occur disproportionately in people of African descent hampering breast cancer (BCa) management and prevention efforts in the population. Our study sought to identify and characterize mutations associated with increased risk of BCa at young age. METHODS: In our study, the spectrum of mutations in BRCA1 and BRCA2 was enumerated in a cohort of 31 African American women of early age at onset breast cancer, with a family history of breast or cancer in general and/or with triple negative breast cancer. To improve the characterization of the BRCA1 and BRCA2 variants, bioinformatics tools were utilized to predict the potential function of each of the variants. RESULTS: Using next generation sequencing methods and in silico analysis of variants, a total of 197 BRCA1 and 266 BRCA2 variants comprising 77 unique variants were identified in 31 patients. Of the 77 unique variants, one (1.3%) was a pathogenic frameshift mutation (rs80359304; BRCA2 Met591Ile), 13 (16.9%) were possibly pathogenic, 34 (44.2%) were benign, and 29 (37.7%) were VUSs. Genetic epidemiological approaches were used to determine the association with variant, haplotype, and phenotypes, such as age at diagnosis, family history of cancer and family history of breast cancer. There were 5 BRCA1 SNPs associated with age at diagnosis; rs1799966 (P=.045; Log Additive model), rs16942 (P=.033; Log Additive model), rs1799949 (P=.058; Log Additive model), rs373413425 (P=.040 and .023; Dominant and Log Additive models, respectively) and rs3765640 (P=.033 Log Additive model). Additionally, a haplotype composed of all 5 SNPs was found to be significantly associated with younger age at diagnosis using linear regression modeling (P=.023). Specifically, the haplotype containing all the variant alleles was associated with older age at diagnosis (OR= 5.03 95% CI=.91-9.14). CONCLUSIONS: Knowing a patient's BRCA mutation status is important for prevention and treatment decision-making. Improving the characterization of mutations will lead to better management, treatment, and BCa prevention efforts in African Americans who are disproportionately affected with aggressive BCa and may inform future precision medicine genomic-based clinical studies.


Assuntos
Afro-Americanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , DNA de Neoplasias/genética , Mutação , Adulto , Idade de Início , Alelos , Proteína BRCA1/metabolismo , Proteína BRCA2/metabolismo , Neoplasias da Mama/etnologia , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Prevalência , Estados Unidos/epidemiologia , Adulto Jovem
15.
Cancer Med ; 6(3): 501-507, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28145091

RESUMO

Precision medicine tools are currently making their way into the clinic and being utilized to diagnose, prognose, and individualize cancer care. The multi-gene expression-based assay, Oncotype DX® (ODX), is a genomic tumor profiling tool that determines the expression of 21 tumor- associated genes; it helps determine the risk for distant recurrence and whether chemotherapy is an appropriate course of treatment in patients with early stage, estrogen receptor (ER) positive, HER2 negative, and lymph node negative (or 1-3 positive lymph nodes) invasive BCa. The aim of this study was to determine the overall utilization and uptake of the ODX genomic test in a cross-sectional analysis of the Virginia Tumor registry, compare utilization in African Americans (AAs) and Caucasian Americans (CAs), and determine the profile of patients referred for testing. Caucasian (89.7%) patients made up the majority of the ODX testers compared to AAs (10.3%) (P < 0.0001). Those who received ODX testing were less likely to have higher grade and higher stage tumors, and were less likely to be ER negative (RR = 0.21, 95% CI: 0.01-0.31), progesterone receptor (PR) negative (RR = 0.35, 95% CI: 0.27-0.45), HER2 amplified (RR = 0.27, 95% CI: 0.17-0.43), or triple negative (RR = 0.21, 95% CI: 0.14-0.33). Of the patients that were eligible (n = 3924), 10.5% (n = 412) received ODX testing. Specifically, 11.7% of the Caucasian patients and 5.1% of AAs patients received ODX testing (P < 0.001). Our analysis confirmed that the utilization of ODX was low and that AAs were much less likely to receive ODX testing.


Assuntos
Afro-Americanos/genética , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu/genética , Genômica/métodos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medicina de Precisão , Prognóstico , Kit de Reagentes para Diagnóstico , Sistema de Registros
16.
J Immigr Minor Health ; 18(5): 1175-1182, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26201692

RESUMO

The objective of this study was to identify predictors of self-reported family health history of breast cancer in an ethnically diverse population of women participating in a breast cancer screening program. Participants completed a self-administered questionnaire about their demography, health, breast health and family health history of breast cancer. The association between family health history of breast cancer and categorical variables were analyzed using the T test, chi square, and multi-nominal logistic regression. Those who were least likely to report a family history of cancer were African Americans (p = 0.02), and immigrant women from South America (p < 0.001) and Africa (p = 0.04). However, 34.4 % reported having a second-degree maternal relative with breast cancer compared to 6.9 % who reported having a second degree paternal relative with breast cancer. Therefore, there is a need to increase efforts to educate families about the importance of collecting and sharing one's family health history.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias da Mama/genética , Predisposição Genética para Doença/etnologia , Anamnese/métodos , Autorrelato , Adulto , Idoso , Idoso de 80 Anos ou mais , Emigrantes e Imigrantes/psicologia , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Alfabetização em Saúde , Humanos , Modelos Logísticos , Anamnese/normas , Pessoa de Meia-Idade , Fatores Socioeconômicos
17.
Anticancer Res ; 35(7): 3811-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26124326

RESUMO

BACKGROUND/AIM: Several studies reported that patients with benign prostatic hyperplasia (BPH) experienced a 10% increased incidence of prostate cancer (PCa) after the first 5 years of diagnosis. We investigated the association between single nucleotide polymorphisms (SNPs) in the promoter of Serine Protease Inhibitor Kazal Type 1 (SPINK1) and the increased risk of BPH and PCa. MATERIALS AND METHODS: We genotyped three SNPs in a cases-control study, including BPH and PCa cases. Multiple logistic regression models were applied to analyze clinical and genotypic data. RESULTS: We found an inverse association between SNP rs10035432 and BPH under the log-additive (p=0.007) model. No association was found between these SNPs and PCa risk. However, we observed a possible association between rs1432982 and lower-grade PCa (p=0.05) under the recessive model. CONCLUSION: SPINK1 promoter variants are likely to be associated with the risk of BPH.


Assuntos
Proteínas de Transporte/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Hiperplasia Prostática/genética , Neoplasias da Próstata/genética , Estudos de Casos e Controles , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/genética , Risco , Inibidor da Tripsina Pancreática de Kazal
18.
Anticancer Res ; 35(5): 2565-70, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25964531

RESUMO

BACKGROUND/AIM: Prostate cancer (PCa) shows disproportionately higher incidence and disease-associated mortality in African Americans. The human crystallin beta B2 (CRYBB2) gene has been reported as one tumor signature gene differentially expressed between African American and European American cancer patients. We investigated the role of CRYBB2 genetic variants in PCa in African Americans. MATERIALS AND METHODS: Subjects comprised of 233 PCa cases and 294 controls. Nine haplotype-tagged single nucleotide polymorphisms (SNPs) in and around the CRYBB2 gene were genotyped by pyrosequencing. Association analyses were performed for PCa with adjustment for age and prostate-specific antigen (PSA), under an additive genetic model. RESULTS: Out of the nine SNPs examined, rs9608380 was found to be nominally associated with PCa (odds ratio (OR)=2.619 (95% confidence interval (CI)=1.156-5.935), p=0.021). rs9306412 was in strong linkage disequilibrium with rs9608380 that showed an association p-value of 0.077. Using ENCODE data, we found rs9608380 mapped to a region annotated with regulatory motifs, such as DNase hypersensitive sites and histone modifications. CONCLUSION: This is the first study to analyze the association between genetic variations in the CRYBB2 gene with PCa. rs9608380, associated with PCa, is a potentially functional variant.


Assuntos
Neoplasias da Próstata/genética , Cadeia B de beta-Cristalina/genética , Adulto , Idoso , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Antígeno Prostático Específico/genética , Neoplasias da Próstata/patologia , Fatores de Risco
19.
Biopreserv Biobank ; 13(2): 98-106, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25825819

RESUMO

PURPOSE: This study examined acceptability of two biobank consent models and evaluated the impact of beliefs about privacy and genetic safeguards on acceptance. METHODS: U.S. adults surveyed online in English and Spanish were randomly assigned to one of two scenarios examining acceptance of broad consent (n=1528), or narrow consent (n=1533). RESULTS: Overall, willingness to provide broad (76%) and narrow (74%) consents were similar. African Americans were as likely as white non-Hispanics to accept narrow consent (72% vs. 77%, p=0.35) but significantly less likely to accept broad consent (69% vs. 81%, p=0.004). Education, insurance, and blood donation history were also related to acceptance. Adjusting for beliefs about privacy and policy protections (Genetic Information Nondiscrimination Act, GINA), the effects of the variables were reduced. Respondents who drew comfort from GINA were more likely to support both consent (both p<0.001); those who believed it is impossible to maintain privacy were less likely to find both broad (p=0.04) and narrow models acceptable (p=0.02). CONCLUSIONS: Choice of consent model matters when engaging diverse populations in biobank research. Beliefs underlying concerns about privacy and genetic protections should be considered when constructing biobank protocols.


Assuntos
Bancos de Espécimes Biológicos/ética , Consentimento Livre e Esclarecido/psicologia , Privacidade/psicologia , Adulto , Afro-Americanos/psicologia , Idoso , Idoso de 80 Anos ou mais , Bancos de Espécimes Biológicos/legislação & jurisprudência , Grupo com Ancestrais do Continente Europeu/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Privacidade/legislação & jurisprudência , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
20.
Anticancer Res ; 35(3): 1549-58, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25750310

RESUMO

BACKGROUND/AIM: Several studies have revealed an association between single nucleotide polymorphisms (SNPs) in the VDR gene and prostate cancer (PCa) risk in European and Asian populations. To investigate whether VDR SNPs are associated with PCa risk in African-American (AA) men, nine VDR SNPs were analyzed in a case-control study. MATERIALS AND METHODS: Multiple and binary logistic regression models were applied to analyze the clinical and genotypic data. RESULTS: rs731236 and rs7975232 were significantly associated with PCa risk (p<0.05). In the analysis of clinical phenotypes, rs731236, rs1544410 and rs3782905 were strongly associated with high PSA level (p<0.05), whereas rs1544410 and rs2239185 showed a statistically significant association with high Gleason score (p<0.05). Haplotype analysis revealed several VDR haplotypes associated with PCa risk. Additionally, a trend existed, where as the number of risk alleles increased in the haplotype, the greater was the association with risk (p-trend=0.01). CONCLUSION: These results suggest that the VDR SNPs may be associated with PCa risk and other clinical phenotypes of PCa in AA men.


Assuntos
Afro-Americanos/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/genética , Receptores de Calcitriol/genética , Idoso , Estudos de Casos e Controles , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Risco
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