BRCA1 gene polymorphism and finger dermatoglyphic patterns in Ghanaian breast cancer patients: a quantitative cross-sectional approach.

Introduction: breast cancer development is linked to mutant single nucleotide polymorphism of breast cancer type 1 (BRCA1) gene usually harboured within exon 11. It has also been linked to finger dermatoglyphics where certain patterns have been associated with breast cancer. This study suggests a possible relationship between finger dermatoglyphic patterns and single nucleotide polymorphism of BRCA1 gene. Methods: in a quantitative cross-sectional approach, finger dermatoglyphic patterns were obtained using the ink method from 70 female breast cancer patients and 70 age-matched apparently healthy females. Approximately 5 ml of venous blood was obtained from each participant from which DNA was extracted from the white blood cells collected after centrifugation. DNA was amplified and sequenced and the data aligned with the wildtype template of BRCA1 gene. Fingerprint patterns were analyzed with Chi-square. Mean frequency of fingerprint patterns was analyzed with independent student's t-test. Differences in data set with p<0.05 were statistically significant. Results: luminal B was the predominant breast cancer molecular subtype among the patients. The predominant fingerprint pattern among breast cancer participants was the loop. Six or more loops had higher frequency among breast cancer females. The predominant BRCA1 gene variant locations were c.34311, c.34320, and c.34321 with c.34311A>C being the predominant variant. Higher percentage frequency of six or more loops in relation to c.34311A>C was observed in apparently healthy females compared to breast cancer females. Conclusion: the study reports for the very first time in Ghana, BRCA1 gene variants and finger dermatoglyphics among breast cancer patients. Although the results are preliminary and inconclusive it creates an avenue for extended studies.

Reduced Serum Circulation of Cell-Free DNA Following Chemotherapy in Breast Cancer Patients.

Breast cancer is the most common malignancy in women, with alarming mortalities. Neoadjuvant treatments employ chemotherapy to shrink tumours to a well-defined size for a better surgical outcome. The current means of assessing effectiveness of chemotherapy management are imprecise. We previously showed that breast cancer patients have higher serum circulating cell-free DNA concentrations. cfDNA is degraded cellular DNA fragments released into the bloodstream. We further report on the utility of cfDNA in assessing the response to chemotherapy and its potential as a monitoring biomarker. A total of 32 newly diagnosed and treatment-naive female breast cancer patients and 32 healthy females as controls were included. Anthropometric, demographic and clinicopathological information of participants were recorded. Each participant donated 5 mL of venous blood from which sera were separated. Blood sampling was carried out before the commencement of chemotherapy (timepoint 1) and after the third cycle of chemotherapy (timepoint 2). qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) was determined. ALU 115 and 247 levels were elevated in cancer patients but were significantly decreased after the third cycle of chemotherapy (T2) compared to T1. DNA integrity increased after the third cycle. Serum cfDNA may provide a relatively inexpensive and minimally invasive procedure to evaluate the response to chemotherapy in breast cancer.

Influence of Lifestyle and Environmental Factors on Semen Quality in Ghanaian Men.

INTRODUCTION: Male infertility is known to contribute about half of all infertility cases. In Ghana, the prevalence of male infertility is higher (15.8%) than in females (11.8%). Sperm quality is associated with the likelihood of pregnancy and known to be the cause of male fertility problems 90% of the time. Exposure to certain environmental factors reduces semen quality in men. The study examined the effects of environmental and lifestyle factors on semen quality in Ghanaian men. MATERIALS AND METHODS: This was a cross-sectional study involving 80 apparent healthy adult males in their reproductive age. Participants were males referred to the laboratory (Immunology Unit of the Korle-Bu Teaching Hospital) for semen analysis test and/or culture and sensitivity. Participants were made to fill out a questionnaire which entailed selected environmental factors (accidents or trauma, exposure to chemicals, radiation, and heat) and lifestyle habits (including alcohol consumption, smoking, and whether participants sat more or less than 4 hours per day). Semen samples were then collected by masturbation into sterile containers and analysed in accordance with WHO guidance for semen analysis within 60 minutes after ejaculation and collection. RESULTS: About 69% of participants had semen pH within the normal range compared to 15% whose pH were lower than 7.2. There was a significantly high number of immotile sperm cells (p value = 0.017) in participants who sat for more than 4 hours as compared to those that sat for less than 4 hours in a day. Active sperm motility and viability showed significant increase (p value = 0.002 and 0.009, respectively) in participants who kept their cell phones in their side pockets. Smoking produced a twofold decrease in sperm count as smokers had a significantly lower sperm count (12.28 ± 10.95 × 106/ml) compared to the smoke-free (23.85 ± 22.14 × 106/ml). For exposure to STDs, no significant differences were recorded among study groups concerning semen quality. CONCLUSION: Sperm quality in Ghanaian men is associated with lifestyle habits. Smoking and sitting for long hours influenced sperm motility and count, respectively. Knowledge of the factors that influence sperm quality in this geographical region can contribute to informed decisions on effective management of infertility in Ghanaian men.

Prospecting for Breast Cancer Blood Biomarkers: Death-Associated Protein Kinase 1 (DAPK1) as a Potential Candidate.

BACKGROUND: Breast cancer is the commonest malignancy in women worldwide. It is estimated to affect approximately 1.5 million women annually and responsible for the greatest number of cancer-related mortalities among women. In 2018, breast cancer mortalities stood at 627,000 women representing approximately 15% of all cancer deaths among women. In Ghana, breast cancer is the second leading cause of cancer deaths, with an incidence of 2,900 cases annually; one of eight women with the disease die. This gives impetus to the fight for improved early detection, treatment, and/management. In this light, we investigated the potential of death-associated protein kinase 1 (DAPK1) as a biomarker for breast cancer. As a tumour suppressor, its expression is activated by several carcinogens to influence cellular pathways that result in apoptosis, autophagy, immune response, and proliferation. AIM: To investigate DAPK1 as a blood biomarker for breast cancer. METHODS: Blood samples of participants diagnosed with breast cancer and healthy controls were collected and processed to obtain serum. Information on age, treatment, diagnosis, and pathology numbers was retrieved from folders. Pathology numbers were used to retrieve breast tissue blocks of patients at the Department of Pathology of the KBTH. Tissue blocks were sectioned and immunohistochemically stained with anti-DAPK1 and counterstained with hematoxylin to determine the DAPK1 expression levels. DAKP1 levels in blood sera were quantified using a commercial anti-DAPK1 ELISA kit. Case and control group means were compared using one-way ANOVA and Chi-square test. Statistical significance was set at p ≤ 0.05. Results and Discussion. DAPK1 levels were higher in sera and breast tissues of breast cancer patients than controls. The augmented DAPK1 expression can be interpreted as a stress response survival mechanism to remediate ongoing deleterious events in the cells orchestrated by carcinogenesis. In the presence of abundant DAPK1, the proliferative power of cells (both cancerous and noncancerous) is increased. This may explain why high DAPK1 expression strongly associates with aggressive breast cancer phenotypes like the ER-negative breast cancers, especially the triple-negative breast cancers (TNBC) which are the most aggressive, fast-growing, and highly metastatic. CONCLUSION: DAPK1 is highly expressed in sera and breast tissues of breast cancer patients than nonbreast cancer participants. The elevated expression of DAKP1 in circulation rather than in breast tissues makes it a candidate for use as a blood biomarker and potential use as therapeutic target in drug development.

Circulating cell-free DNA integrity as a diagnostic and prognostic marker for breast and prostate cancers.

BACKGROUND: Cancer incidence and its related mortality is rising and is currently the second leading cause of death globally. In Africa, breast and prostate cancer in females and males, respectively, are the worst globally. However, biomarkers for their early detection and prognosis are not well developed. This study sought to investigate circulating cell-free DNA (ccfDNA) integrity and its potential utility as diagnostic and/or prognostic biomarker. Circulating cell-free DNA (ccfDNA) is degraded DNA fragments released into the blood plasma. In healthy individuals, the source of ccfDNA is solely apoptosis, producing evenly sized shorter DNA fragments. In cancer patients, however, necrosis produces uneven longer cell-free DNA fragments in addition to the shorter fragments originating from apoptosis. DNA integrity, expressed as the ratio of longer fragments to total DNA, may be clinically useful for the detection of breast and prostate cancer progression. METHODS: Sixty-four (64) females, consisting of 32 breast cancer patients and 32 controls, and 61 males (31 prostate cancer patients and 30 controls) were included in the study. Each participant donated 5 ml peripheral blood from which sera were separated. Real-time qPCR was performed on the sera to quantify ALU 115 and 247 levels, and DNA integrity (ALU247/ALU115) determined. RESULTS & CONCLUSION: ALU species 115 and 247 levels in serum were elevated in breast and prostate cancer patients compared to their counterpart healthy controls. DNA integrity was higher in prostate cancer patients than in the control, but in breast cancer patients was lower compared to their controls. In prostate but not in breast cancers, DNA integrity increased with disease severity and higher staging.

Safety and effectiveness of antimalarial therapy in sickle cell disease: a systematic review and network meta-analysis.

BACKGROUND: About 80% of all reported sickle cell disease (SCD) cases in children anually are recorded in Africa. Although malaria is considered a major cause of death in SCD children, there is limited data on the safety and effectiveness of the available antimalarial drugs used for prophylaxis. Also, previous systematic reviews have not provided quantitative measures of preventive effectiveness. The purpose of this research was to conduct a systematic review and meta-analysis of the available literature to determine the safety and effectiveness of antimalarial chemoprophylaxis used in SCD patients. METHODS: We searched in PubMed, Medline, CINAHL, POPLine and Cochrane library, for the period spanning January 1990 to April 2018. We considered randomized or quasi-randomized controlled trials comparing any antimalarial chemoprophylaxis to, 1) other antimalarial chemoprophylaxis, 2) placebo or 3) no intervention, in SCD patients. Studies comparing at least two treatment arms, for a minimum duration of three months, with no restriction on the number of patients per arm were reviewed. The data were extracted and expressed as odds ratios. Direct pairwise comparisons were performed using fixed effect models and the heterogeneity assessed using the I-square. RESULTS: Six qualified studies that highlighted the importance of antimalarial chemoprophylaxis in SCD children were identified. In total, seven different interventions (Chloroquine, Mefloquine, Mefloquine artesunate, Proguanil, Pyrimethamine, Sulfadoxine-pyrimethamine, Sulfadoxine-pyrimethamine amodiaquine) were evaluated in 912 children with SCD. Overall, the meta-analysis showed that antimalarial chemoprophylaxis provided protection against parasitemia and clinical malaria episodes in children with SCD. Nevertheless, the risk of hospitalization (OR = 0.72, 95% CI = 0.267-1.959; I2 = 0.0%), blood transfusion (OR = 0.83, 95% CI = 0.542-1.280; I2 = 29.733%), vaso-occlusive crisis (OR = 19, 95% CI = 1.713-2.792; I2 = 93.637%), and mortality (OR = 0.511, 95% CI = 0.189-1.384; I2 = 0.0%) did not differ between the intervention and placebo groups. CONCLUSION: The data shows that antimalarial prophylaxis reduces the incidence of clinical malaria in children with SCD. However, there was no difference between the occurrence of adverse events in children who received placebo and those who received prophylaxis. This creates an urgent need to assess the efficacy of new antimalarial drug regimens as potential prophylactic agents in SCD patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42016052514).

Higher serum concentrations of vimentin and DAKP1 are associated with aggressive breast tumour phenotypes in Ghanaian women.

BACKGROUND: Breast cancer, the most commonly diagnosed cancer among women and leading cause of cancer-related deaths worldwide, exhibits aggressive behavior in indigenous African women evidenced by high histologic grade tumours with low hormone receptor positivity. Aggressive breast cancers grow quickly, easily metastasize and recur and often have unfavourable outcomes. The current study investigated candidate genes that may regulate tumour aggression in Ghanaian women. We hypothesize that increased expression and function of certain genes other than the widely-held view attributing breast cancer aggression in African populations to their younger population age may be responsible for the aggressive nature of tumours. METHODS: Employing ELISA, we assayed for vimentin and death-associated protein kinase 1 (DAPK1) from thawed archived (stored at -80 °C) serum samples obtained from 40 clinically confirmed Ghanaian breast cancer patients and 40 apparently healthy controls. Patients' clinical records and tumour parameters matching the samples were retrieved from the database of the hospital. ANOVA was used to compare means of serum protein concentration among groups while Chi-square analysis was used for the categorical data sets with p-value ≤0.05 considered significant. Multiple logistic regression analysis was conducted to determine the association between protein concentration and tumour parameters. RESULTS: Of the 80 samples, 27 (33.8%) and 53 (66.2%) were from young (<35 years) and old (≥35 years), respectively. Vimentin and DAPK1 concentration were higher in patients than controls with higher levels in "young" age group than "old" age group. Vimentin concentration was highest in grade 3 tumours followed by grade 2 and 1 but that for DAPK1 was not significant. For vimentin, tumour area strongly correlated with tumour grade (r = 0.696, p < 0.05) but weakly correlated with tumour stage (r = 0.420, p < 0.05). Patient's age correlated with DAPK1 concentration (r = 0.393, p < 0.05). DAPK1 serum levels weakly correlated with cancer duration (r = 0.098, p = 0.27) and tumour size (r = 0.40, p < 0.05). CONCLUSION: Serum concentration of Vimentin and DAPK1 are elevated in Ghanaian breast cancer patients. This may be partly responsible for aggressive nature of the disease among the population. Vimentin and DAPK1 should be explored further as potential breast cancer biomarkers in Africans.

Overexpression of JAKMIP1 associates with Wnt/ß-catenin pathway activation and promotes cancer cell proliferation in vitro.

JAKMIP1 is a member of the recently characterized JAKMIP1 family of proteins. It has been suggested that JAKMIP1 may play a role in various cell programs, such as cytoskeleton rearrangement, cell polarization, intracellular transport or even cell signaling activities. We examined its protein expression in tumor and followed it with a model that captures its impact on activities of some tumor-linked signaling pathways as well as how its upregulation affects cell proliferation. Here, we demonstrate that JAKMIP1 is highly expressed in tumor samples than in normal tissues. Additionally, higher expression of this protein may activate Wnt signaling activity, potentiate beta-catenin accumulation and enhance proliferation of cancer cells.