Women of sub-Saharan African descent have disproportionately higher incidence of Triple Negative Breast Cancer (TNBC), and TNBC-specific mortality. Population comparative studies show racial differences in TNBC biology, including higher prevalence of basal-like and Quadruple-Negative subtypes in African Americans (AA). However, previous investigations relied on self-reported race (SRR) of primarily United States (US) populations. Due to heterogenous genetic admixture, and biological consequences of social determinants, the true association of African ancestry with TNBC biology is unclear. To address this, we conducted RNAseq on an international cohort of AAs, west and east Africans with TNBC. Using comprehensive genetic ancestry estimation in this African-enriched cohort, we found expression of 613 genes associated with African ancestry and 2000+ associated with regional African ancestry. A subset of African-associated genes also showed differences in normal breast tissue. Pathway enrichment and deconvolution of tumor cellular composition revealed tumor-associated immunological profiles are distinct in patients of African descent.

Background: Our objective was to assess racial differences in the 5-year relative survival rates (RSRs) of Cervical Cancer (CerCancer) by stage at diagnosis, between Black and White women, living in Alabama, USA. Methods: Data for 3484 Blacks and 21,059 Whites diagnosed with CerCancer were extracted from the 2004 to 2013 Surveillance, Epidemiology, and End Results (SEER) database. We incorporated age groups, CerCancer stages, county, and year of diagnosis to compare the RSR between Blacks and Whites, using SEER*Stat software. Results: In urban, Black Belt (BB) and other rural counties, Whites diagnosed with localized stage of CerCancer always had better chances of survival because their RSRs were always more than 77%, compared to Blacks. Only exception was in Blacks living in other rural counties, who had a significantly higher RSR of 83.8% (95% Cl, 74.2-90.1). Which was the same as in Whites (83.8% (95% CI 74.5-89.9) living in BBC. Although, in other rural counties, Whites had a slightly lower RSR of 83.7% (95% CI 79.9-86.8%), their RSR was better compared to Blacks and Whites living in BB and other rural counties who had slightly higher RSRs of 83.8%. This was due to statistical precision, which depended on their larger sample size and a lower variability therefore, more reliability resulting in a tighter confidence interval with a smaller margin of error. In all the three county groups, Whites 15-44 years old diagnosed with localized stage of CerCancer had a higher RSR of 93.6% (95% CI 91.4-95.2%) for those living in urban and BB counties, and 94.6% (95% CI 93.6-95.4) for those living in other rural counties. The only exception was in Blacks 65-74 years old living in other rural counties who had the highest RSR of 96.9% (95% Cl, 82.9-99.5). However, Whites were considered to have a better RSR. This was also due to the statistical precision as mentioned above. Conclusion: There were significant racial differences in the RSRs of CerCancer. Overall, Black women experienced the worst RSRs compared to their White counterparts.

Large-scale efforts to identify breast cancer (BC) risk alleles have historically taken place among women of European ancestry. Recently, there are new efforts to verify if these alleles increase risk in African American (AA) women as well. We investigated the effect of previously reported AA breast cancer and triple-negative breast cancer (TNBC) risk alleles in our African-enriched International Center for the Study of Breast Cancer Subtypes (ICSBCS) cohort. Using case–control, case-series and race-nested approaches, we report that the Duffy-null allele (rs2814778) is associated with TNBC risk (OR = 3.814, p = 0.001), specifically among AA individuals, after adjusting for self-indicated race and west African ancestry (OR = 3.368, p = 0.007). We have also validated the protective effect of the minor allele of the ANKLE1 missense variant rs2363956 among AA for TNBC (OR = 0.420, p = 0.005). Our results suggest that an ancestry-specific Duffy-null allele and differential prevalence of a polymorphic gene variant of ANKLE1 may play a role in TNBC breast cancer outcomes. These findings present opportunities for therapeutic potential and future studies to address race-specific differences in TNBC risk and disease outcome.

Background: Docetaxel (DOC), or Taxotere, is an anthracycline antibiotic used to treat multiple types of cancer. It is a first-line chemotherapy treatment for patients with metastasized, hormone-resistant prostate cancer (PCa) or for patients with high-risk, localized PCa that could benefit from early chemotherapy treatment. Previously, we showed that stearidonic acid (SDA), an omega-3 fatty acid, enhances the cytotoxicity of doxorubicin (DOX) in human PCa cells. This observation suggests that PCa therapies using SDA and chemotherapeutic drugs in combination offer attractive possibilities for developing treatments that ameliorate toxic side effects of some commonly used chemotherapy drugs.Objectives: We used androgen-resistant PC3 and DU 145 cells derived from human prostate cancer to quantify the effects of combined SDA and DOC on proliferation/viability and on the production of pro-apoptotic caspases 9 and 3. We also compared the effects of SDA with those of BAY, a pharmacological inhibitor of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), in androgen-sensitive LNCaP cells. Finally, we qualitatively and quantitatively assessed the drug combination on androgen receptor (AR) and peroxisome proliferator-activated receptor gamma (PPARγ) expression in LNCaP and PC3 cells, respectively.Methods: The half maximal inhibitory concentration (IC50) and combination indices of SDA and DOC in PC3 and DU 145 cells were determined using the MTT cell viability assay. To quantify the effects of SDA and BAY on NF-ĸB activity, we used luciferase reporter assays in LNCaP cells that were stably transduced with lentiviral vectors carrying NF-ĸB response element sequence upstream of the luciferase gene sequence. AR and PPARγ expression were assessed by western blotting and immunocytochemistry. We considered caspase 9 and 3 cleavage to be apoptosis markers and determined the drug combination effect on the extent of that cleavage by western blot analysis.Results: The cytotoxic effects of DOC were synergistically enhanced by SDA when the two were added to DU145 and PC3 cell cultures. Combination index (CI) analyses based on the Chou-Talalay method and mass action law showed synergistic interaction with CI <1. SDA suppressed TNFα-induced NF-κB activity similarly to BAY. The SDA/DOC combination down regulated testosterone (T)-induced AR and troglitazone-induced PPARγ protein expression when compared to using the drugs singly. Similarly, the SDA/DOC combination induced caspase 9 and 3 production and cleavage suggesting apoptosis induction. Like our DOX studies, this work provides proof-of-concept for using SDA and DOC in combination to reduce the dose, and therefore the toxicity, of DOC and possibly increasing the survival benefit in DOC clinical translation studies.