MYC amplification in subtypes of breast cancers in African American women

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 \u3c 14%), Luminal B (ER or PR+, Ki-67 = \u3e 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 \u3e 1). Statistically significant associations were found between MYC amplification and HER2-amplified BCa, and Luminal B subtypes of BCa (p \u3c 0.0001), stage (p \u3c 0.001), metastasis (p \u3c 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

Breast cancer prognosis for young patients

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\u27s 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

DHPLC elution patterns of vdr PCR products can predict prostate cancer susceptibility in african american men

Background/Aim: Denaturing high-performance liquid chromatography (DHPLC) is a technique that is used to detect mutations. The aim of the present study was to determine whether DHPLC elution patterns of vitamin D receptor (VDR) gene PCR products can serve as indicators of susceptibility to prostate cancer (PCa) risk. Materials and Methods: DNA samples of PCa cases and controls were screened for mutations and/or polymorphisms in coding exons of VDR gene using DHPLC analysis. Logistic regression, phi-coefficient (φ), and Backward Wald models were used to analyze the data. Results: Similar elution patterns of exons 1, 6, 7 and 9 along with higher prevalence of heteroduplex DNA were observed in PCa samples than in controls. Exons 4 and 8 had highly significant protective effects (p\u3c0.05). Whereas, exons 5, 7, and 9 were perfectly positively correlated with PCa risk (φ=1), thus presenting candidate exons significantly associated with susceptibility to PCa. Conclusion: DHPLC elution patterns of the selected exons could be useful to predict susceptibility to develop PCa

Use of tanning potential as a predictor for prostate cancer risk in African-American men

Background/Aim: Vitamin D deficiency in African-Americans is common due to the high melanin content of the skin that reduces the absorption of UV radiation. To determine if there is a correlation between UV exposure, tanning potential and vitamin D with prostate cancer (PC) risk, we conducted a case-control study of 183 African-American men aged 40 years and older residing in the Washington, DC area. Patients and Methods: PC status was described as a binary variable as the presence or absence of cancer and the environmental factors as continuous variables. We used a logistic regression model describing PC as the response, while age, tanning potential, sunlight and vitamin D were treated as the predictors. Results: Men aged 60 years and older had a seven-fold increased risk for developing PC compared to those aged 50 years and less (p\u3c0.003). Tanning potential was a significant (p=0.05) risk factor for PC, while sunlight exposure and vitamin D were not. Tanning potential was also significant (p=0.044) when adjusted for vitamin D and age. However, tanning potential was only marginally significant when adjusted for sunlight exposure (p=0.064) Conclusion: The findings of this study indicate that tanning potential may be a predictor for PC risk in African-American men

A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer

Background: To investigate the global expression profile of miRNAs, their impact on cellular signaling pathways, and their association with poor prognostic parameters in African-American (AA) patients with triple negative breast cancer (TNBC). Methods: Twenty-five samples of AA TNBC patients were profiled for global miRNA expression and stratified considering three clinical-pathological parameters: tumor size, lymph node (LN), and recurrence (REC) status. Differential miRNA expression analysis was performed for each parameter, and their discriminatory power was determined by Receiver Operating Characteristic (ROC) curve analysis. KMplotter was assessed to determine the association of the miRNAs with survival, and functional enrichment analysis to determine the main affected pathways and miRNA/mRNA target interactions. Results: A panel of eight, 23 and 27 miRNAs were associated with tumor size, LN, and REC status, respectively. Combined ROC analysis of two (miR-2117, and miR-378c), seven (let-7f-5p, miR-1255b-5p, miR-1268b, miR-200c-3p, miR-520d, miR-527, and miR-518a-5p), and three (miR-1200, miR-1249-3p, and miR-1271-3p) miRNAs showed a robust discriminatory power based on tumor size (AUC = 0.917), LN (AUC = 0.945) and REC (AUC = 0.981) status, respectively. Enrichment pathway analysis revealed their involvement in proteoglycans and glycan and cancer-associated pathways. Eight miRNAs with deregulated expressions in patients with large tumor size, positive LN metastasis, and recurrence were significantly associated with lower survival rates. Finally, the construction of miRNA/mRNA networks based in experimentally validated mRNA targets, revealed nodes of critical cancer genes, such as AKT1, BCL2, CDKN1A, EZR and PTEN. Conclusions: Altogether, our data indicate that miRNA deregulated expression is a relevant biological factor that can be associated with the poor prognosis in TNBC of AA patients, by conferring to their TNBC cells aggressive phenotypes that are reflected in the clinical characteristics evaluated in this study

Vitamin D receptor genetic polymorphisms are associated with PSA level, gleason score and prostate cancer risk in african-american men

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\u3c0.05). In the analysis of clinical phenotypes, rs731236, rs1544410 and rs3782905 were strongly associated with high PSA level (p\u3c0.05), whereas rs1544410 and rs2239185 showed a statistically significant association with high Gleason score (p\u3c0.05). 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 (ptrend= 0.01). Conclusion: These results suggest that the VDR SNPs may be associated with PCa risk and other clinical pheno types of PCa in AA men

Estrogen Receptor/Progesterone Receptor-Negative Breast Cancers of Young African-American Women Have a Higher Frequency of Methylation of Multiple Genes than Those of Caucasian Women

Purpose: To provide a molecular rationale for negative prognostic factors more prevalent in African-American (AA) than Caucasian (Cau) women, we investigated the frequency of promoter hypermethylation in invasive ductal breast cancers in the two races. Experimental Design: HIN-1, Twist, Cyclin D2, RAR-β, and RASSF1A were analyzed in DNA from 67 AA and 44 Can invasive ductal breast cancers, stratified by age and estrogen receptor/progesterone receptor (ER/PR) status, by methylation-specific PCR. Hierarchical multiple logistic regression analysis was applied to determine estimated probabilities of methylation. Expression of HIN-1 mRNA was analyzed by in situ hybridization and quantitative reverse transcribed PCR. Results: Significant differences between races were observed in the ER-/PR-, age \u3c 50 subgroup; AA tumors had higher frequency of methylation (P \u3c 0.001) in four of five genes as compared with Cau and also a higher prevalence (80 versus 0%; P \u3c 0.005) of three or more methylated genes per tumor. No differences in gene methylation patterns were observed across the two races for ER+/PR+ tumors in all ages and ER-/PR- tumors in age \u3e 50. ER+/PR+ status was associated with higher frequency of methylation in Cau tumors of all ages but only with the age \u3e 50 subgroup in AA. Frequent Cyclin D2 methylation was significantly associated (P = 0.01) with shorter survival time. Conclusion: ER-/PR-, age \u3c 50 tumors in AA women, have a significantly higher frequency of hypermethylation than in those of Cau women. Comparative studies, such as these, could provide a molecular basis for differences in tumor progression and pathology seen in the two races

Kernel-Based Microfluidic Constriction Assay for Tumor Sample Identification

A high-throughput multiconstriction microfluidic channels device can distinguish human breast cancer cell lines (MDA-MB-231, HCC-1806, MCF-7) from immortalized breast cells (MCF-10A) with a confidence level of ∼81–85% at a rate of 50–70 cells/min based on velocity increment differences through multiconstriction channels aligned in series. The results are likely related to the deformability differences between nonmalignant and malignant breast cells. The data were analyzed by the methods/algorithms of Ridge, nonnegative garrote on kernel machine (NGK), and Lasso using high-dimensional variables, including the cell sizes, velocities, and velocity increments. In kernel learning based methods, the prediction values of 10-fold cross-validations are used to represent the difference between two groups of data, where a value of 100% indicates the two groups are completely distinct and identifiable. The prediction value is used to represent the difference between two groups using the established algorithm classifier from high-dimensional variables. These methods were applied to heterogeneous cell populations prepared using primary tumor and adjacent normal tissue obtained from two patients. Primary breast cancer cells were distinguished from patient-matched adjacent normal cells with a prediction ratio of 70.07%–75.96% by the NGK method. Thus, this high-throughput multiconstriction microfluidic device together with the kernel learning method can be used to perturb and analyze the biomechanical status of cells obtained from small primary tumor biopsy samples. The resultant biomechanical velocity signatures identify malignancy and provide a new marker for evaluation in risk assessment

Kernel-Based Microfluidic Constriction Assay for Tumor Sample Identification

A high-throughput multiconstriction microfluidic channels device can distinguish human breast cancer cell lines (MDA-MB-231, HCC-1806, MCF-7) from immortalized breast cells (MCF-10A) with a confidence level of ∼81–85% at a rate of 50–70 cells/min based on velocity increment differences through multiconstriction channels aligned in series. The results are likely related to the deformability differences between nonmalignant and malignant breast cells. The data were analyzed by the methods/algorithms of Ridge, nonnegative garrote on kernel machine (NGK), and Lasso using high-dimensional variables, including the cell sizes, velocities, and velocity increments. In kernel learning based methods, the prediction values of 10-fold cross-validations are used to represent the difference between two groups of data, where a value of 100% indicates the two groups are completely distinct and identifiable. The prediction value is used to represent the difference between two groups using the established algorithm classifier from high-dimensional variables. These methods were applied to heterogeneous cell populations prepared using primary tumor and adjacent normal tissue obtained from two patients. Primary breast cancer cells were distinguished from patient-matched adjacent normal cells with a prediction ratio of 70.07%–75.96% by the NGK method. Thus, this high-throughput multiconstriction microfluidic device together with the kernel learning method can be used to perturb and analyze the biomechanical status of cells obtained from small primary tumor biopsy samples. The resultant biomechanical velocity signatures identify malignancy and provide a new marker for evaluation in risk assessment