Breast cancer in East Africa: Prevalence and spectrum of germline SNV/indel and CNVs in BRCA1 and BRCA2 genes among breast cancer patients in Tanzania.

BACKGROUND: Growing prevalence and aggressiveness of breast cancer (BC) among East African women strongly indicate that the genetic risk factor implicated in the etiology of the disease may have a key role. Germline pathogenic variants in BRCA1 and BRCA2 (BRCA1/2) are known to increase the lifetime risk of BC. This study investigated the prevalence and spectrum of germline single nucleotide variant/insertion and deletion (SNV/indel), and copy number variations (CNVs) in BRCA1/2 among Tanzanian BC patients, and evaluated the associations of identified variants with patient's socio-demographic and histopathological characteristics. METHODS: One hundred BC patients were examined for BRCA1/2 variants using next-generation sequencing (NGS). Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) assay were performed for the confirmation of SNV/indel and CNVs, respectively. RESULTS: Six germline SNV/indel pathogenic variants were detected from six unrelated patients. Five of these variants were identified in BRCA1, and one in BRCA2. We also identified, in one patient, one variant of uncertain clinical significance (VUS). CNV was not detected in any of the BC patients. Furthermore, we found that in our cohort, BRCA1/2 variant carriers were triple-negative BC patients (p = 0.019). CONCLUSIONS: Our study provides first insight into BC genetic landscape by the use of NGS in the under-represented East African Tanzanian populations. Our findings support the importance of genetic risk factors in BC etiology in Tanzania and showed a relatively high overall prevalence (6%) of germline BRCA1/2 pathogenic variants in BC patients. Therefore, our results indicate that BRCA1/2 pathogenic variants may well contribute to BC incidence in Tanzania. Thus, the identification of frequent variants in BRCA1/2 genes will enable implementation of rapid, inexpensive population-specific BRCA1/2 genetic testing, particularly for triple-negative BC patients known for their high prevalence in Tanzania. This will, in turn, greatly contributes to provide effective therapeutic strategies.

The interplay between XPG-Asp1104His polymorphism and reproductive risk factors elevates risk of breast cancer in Tanzanian women: A multiple interaction analysis.

BACKGROUND: Reproductive history and genetics are well-known risk factors of breast cancer (BC). Little is known about how these factors interact to effect BC. This study investigated the association of ten polymorphisms in DNA repair genes with BC susceptibility in the Tanzanian samples and further analyzed the association between reproductive risk factors and disease risk METHODS: A hospital-based case-control study in 263 histopathological confirmed BC patients and 250 age-matched cancer-free controls was carried out. Allelic, genotypic, and haplotype association analyses were executed. Also, multifactor dimensionality reduction (MDR), and interaction dendrogram approaches were performed. RESULTS: The frequency of genotypic and allelic variants of XRCC1-Arg399Gln (rs25487), XRCC2-Arg188His (rs3218536), XRCC3-Thr241Met (rs861539), XPG-Asp1104His (rs17655), and MSH2-Gly322Asp (rs4987188) were significantly different between the groups (p < 0.05). Moreover, XRCC1-Arg399Gln (rs25487), XRCC3-Thr241Met (rs861539), and XPG-Asp1104His (rs17655) were associated with the increased risk of BC in co-dominant, dominant, recessive, and additive genetic-inheritance models (p < 0.05). XRCC1-Arg/Gln genotype indicated a 3.1-fold increased risk of BC in pre-menopausal patients (p = 0.001) while XPG-His/His genotype showed a 1.2-fold increased risk in younger BC patients (<40 years) (p = 0.028). Asp/His+His/His genotypes indicated a 1.3-fold increased risk of BC in PR+ patients and a 1.1-fold decreased risk of BC in luminal-A patients (p = 0.014, p = 0.020, respectively). MDR analysis revealed a positive interaction between BC and the XPG-Asp1104His (rs17655) together with family history of cancer in the first-degree relatives. Dendrogram analysis indicated that the XPG-Asp1104His (rs17655) and family history of cancer in first-degree relatives were significantly synergistic and might be associated with an elevated risk of BC in Tanzania. CONCLUSIONS: The XPG-Asp1104His (rs17655) might exert both independent and interactive effects on BC development in the Tanzanian women.

The distribution of reproductive risk factors disclosed the heterogeneity of receptor-defined breast cancer subtypes among Tanzanian women.

BACKGROUND: Recent epidemiological studies suggest that reproductive factors are associated with breast cancer (BC) molecular subtypes. However, these associations have not been thoroughly studied in the African populations. The present study aimed to investigate the prevalence of BC molecular subtypes and assess their association with reproductive factors in Tanzanian BC patients. METHODS: This hospital-based case-only cross-sectional study consisted of 263 histologically confirmed BC patients in Tanzania. Clinico-pathological data, socio-demographic characteristics, anthropometric measurements, and reproductive risk factors were examined using the Chi-square test and one-way ANOVA. The association among reproductive factors and BC molecular subtypes was analyzed using multinomial logistic regression. The heterogeneity of the associations was assessed using the Wald test. RESULTS: We found evident subtype heterogeneity for reproductive factors. We observed that post-menopausal status was more prevalent in luminal-A subtype, while compared to luminal-A subtype, luminal-B and HER-2 enriched subtypes were less likely to be found in post-menopausal women (OR: 0.21, 95%CI 0.10-0.41, p = 0.001; OR: 0.39, 95%CI 0.17-0.89, p = 0.026, respectively). Also, the luminal-B subtype was more likely to be diagnosed in patients aged ≤ 40 years than the luminal-A subtype (OR: 2.80, 95%CI 1.46-5.32, p = 0.002). Women who had their first full-term pregnancy at < 30 years were more likely to be of luminal-B (OR: 2.71, 95%CI 1.18-4.17, p = 0.018), and triple-negative (OR: 2.28, 95%CI 1.02-4.07, p = 0.044) subtypes relative to luminal-A subtype. Furthermore, we observed that breastfeeding might have reduced odds of developing luminal-A, luminal-B and triple-negative subtypes. Women who never breastfed were more likely to be diagnosed with luminal-B and triple-negative subtypes when compared to luminal-A subtype (OR: 0.46, 95%CI 0.22-0.95, p = 0.035; OR: 0.41, 95%CI 0.20-0.85, p = 0.017, respectively). . CONCLUSION: Our results are the first data reporting reproductive factors heterogeneity among BC molecular subtypes in Tanzania. Our findings suggest that breast-feeding may reduce the likelihood of developing luminal-A, luminal-B, and triple-negative subtypes. Meanwhile, the first full-term pregnancy after 30 years of age could increase the chance of developing luminal-A subtype, a highly prevalent subtype in Tanzania. More interventions to promote modifiable risk factors across multiple levels may most successfully reduce BC incidence in Africa.

Asthma and COVID-19: Emphasis on Adequate Asthma Control.

Asthmatics are at an increased risk of developing exacerbations after being infected by respiratory viruses such as influenza virus, parainfluenza virus, and human and severe acute respiratory syndrome coronaviruses (SARS-CoV). Asthma, especially when poorly controlled, is an independent risk factor for developing pneumonia. A subset of asthmatics can have significant defects in their innate, humoral, and cell-mediated immunity arms, which may explain the increased susceptibility to infections. Adequate asthma control is associated with a significant decrease in episodes of exacerbation. Because of their wide availability and potency to promote adequate asthma control, glucocorticoids, especially inhaled ones, are the cornerstone of asthma management. The current COVID-19 pandemic affects millions of people worldwide and possesses mortality several times that of seasonal influenza; therefore, it is necessary to revisit this subject. The pathogenesis of SARS-CoV-2, the virus that causes COVID-19, can potentiate the development of acute asthmatic exacerbation with the potential to worsen the state of chronic airway inflammation. The relationship is evident from several studies that show asthmatics experiencing a more adverse clinical course of SARS-CoV-2 infection than nonasthmatics. Recent studies show that dexamethasone, a potent glucocorticoid, and other inhaled corticosteroids significantly reduce morbidity and mortality among hospitalized COVID-19 patients. Hence, while we are waiting for more studies with higher level of evidence that further narrate the association between COVID-19 and asthma, we advise clinicians to try to achieve adequate disease control in asthmatics as it may reduce incidences and severity of exacerbations especially from SARS-CoV-2 infection.

Draft Genome Sequence of Limnospira sp. Strain BM01, Isolated from a Hypersaline Lake of the Momela Ecosystem in Tanzania.

The genus Limnospira includes cyanobacterial species used for industrial production of dietary supplements and nutraceutical agents. The metagenome-assembled genome of Limnospira sp. strain BM01 from Big Momela Lake, Tanzania, was 6,228,312 bp long with a GC content of 44.8% and carried 4,921 proteins and 52 RNA genes, including 6 rRNA genes.

Factors associated with risk of preterm delivery in Tanzania: A case-control study at Muhimbili National Hospital.

OBJECTIVE: To determine factors associated with risk of preterm delivery among pregnant women delivering at Muhimbili National Hospital in Tanzania. METHODS: A 1:1 case-control study was conducted to assess maternal sociodemographic, lifestyle, and current and previous obstetric factors associated with risk of preterm delivery. Mothers of preterm infants were regarded as cases and those of term infants were controls. Chi-square test and logistic regression were used to assess association between the factors and risk of preterm delivery. RESULTS: A total of 222 case-control pairs were studied. Maternal type of employment (P = 0.039), previous preterm delivery (P = 0.002), previous spontaneous abortion (P = 0.004), uterine scar (P < 0.001), parity (P = 0.034), number of prenatal care visits (P = 0.032), premature rupture of membranes (PROM) (P < 0.001), placenta previa (P = 0.002), bleeding during second trimester (P = 0.004), pre-eclampsia (P < 0.001), and maternal anemia (P = 0.033) were associated with risk of preterm delivery. The main risk factors associated with preterm delivery included previous preterm delivery (odds ratio [OR] 13.23, 95% confidence interval [CI] 1.72-101.95), placenta previa (OR 12.63, 95% CI 1.63-97.98), and PROM (OR 8.77, 95% CI 1.33-4.60). CONCLUSION: Close monitoring of pregnant women who present any of the risk factors is important to prevent or reduce the risk of preterm delivery in Tanzania.

Molecular approach to confirm traditional identification of Radopholus similis sampled in Tanzania.

Banana (Musa spp. L.) is an important staple food and cash crop for about 30% of the population in Tanzania; however, the burrowing plant-parasitic nematode Radopholus similis causes black head disease and toppling in banana plants, which results in yield losses. We collected and identified 80 specimens of R. similis from four agro-ecological zones in Tanzania using morphological characters. We then used universal and specific R. similis primers to amplify the small subunit, internal transcribed spacer and large subunit of ribosomal DNA regions of these specimens. The amplicons were subsequently sequenced and analyzed using Bayesian inference. We identified two major clades, one that comprised all R. similis sequences derived from this study and another that included R. similis and Radopholus spp. sequences obtained from GenBank, indicating the separation of this species from congeneric sequences. Our findings provide a useful, simple and rapid method for identifying burrowing nematodes. This outcome could contribute to the development of permanent, integrated pest management strategies for the control of R. similis in banana and other crops in order to reduce associated yield losses in Tanzania. To our knowledge, this is the first study of nematodes to use combined morphological and molecular methods for the identification of R. similis in Tanzania.Banana (Musa spp. L.) is an important staple food and cash crop for about 30% of the population in Tanzania; however, the burrowing plant-parasitic nematode Radopholus similis causes black head disease and toppling in banana plants, which results in yield losses. We collected and identified 80 specimens of R. similis from four agro-ecological zones in Tanzania using morphological characters. We then used universal and specific R. similis primers to amplify the small subunit, internal transcribed spacer and large subunit of ribosomal DNA regions of these specimens. The amplicons were subsequently sequenced and analyzed using Bayesian inference. We identified two major clades, one that comprised all R. similis sequences derived from this study and another that included R. similis and Radopholus spp. sequences obtained from GenBank, indicating the separation of this species from congeneric sequences. Our findings provide a useful, simple and rapid method for identifying burrowing nematodes. This outcome could contribute to the development of permanent, integrated pest management strategies for the control of R. similis in banana and other crops in order to reduce associated yield losses in Tanzania. To our knowledge, this is the first study of nematodes to use combined morphological and molecular methods for the identification of R. similis in Tanzania.

Polymorphisms of the Chicken Mx Gene Promoter and Association with Chicken Embryos' Susceptibility to Virulent Newcastle Disease Virus Challenge.

Newcastle disease is a devastating viral disease of chicken in low- and middle-income countries where the backyard production system is predominant. Marker-assisted selection of chickens that are resistant to Newcastle disease virus (NDV) is the promising strategy that needs to be explored. The aim of the present study was to investigate polymorphisms of the promoter region of the chicken Mx gene and association with Kuroiler, Sasso, and local Tanzanian chicken embryos' survival variability to virulent NDV infection. Chicken embryos were initially challenged with a minimum lethal dose of virulent NDV suspension and then were followed over time to gather information on their survival variability. Using the survival data, high and less susceptible cohorts were established, and a total of 88 DNA samples from high and less susceptible groups were genotypes by sequencing. Five single-nucleotide polymorphisms (SNPs), which were previously reported, were detected. Interestingly, for the first time, the findings demonstrated the association of the promoter region of chicken myxovirus-resistance (Mx) gene polymorphisms with chicken embryos' susceptibility to the virulent NDV challenge. At the genotypic level, the SNP4 G > A mutation that was located within the IFN-stimulating response element was associated (LR: 6.97, P=0.03) with chicken embryos' susceptibility to the virulent NDV challenge. An allele G frequency was higher in the less susceptible cohort, whereas an allele A frequency was higher in the high susceptible cohort. At the haplotype level, the haplotype group ACGC was associated (OR: 9.8, 95% CI: 1.06-79.43, P=0.042) with the same trait and had a resistant effect. In conclusion, the results have demonstrated the association of chicken Mx gene promoter polymorphisms and chicken embryos' survival variability to the virulent NDV challenge, and the information is useful for breeding programs designed to develop chicken genotypes that are resistant to Newcastle disease virus.

Gene expression regulation in the plant growth promoting Bacillus atrophaeus UCMB-5137 stimulated by maize root exudates.

Despite successful use of Plant Growth Promoting Rhizobacteria (PGPR) in agriculture, little is known about specific mechanisms of gene regulation facilitating the effective communication between bacteria and plants during plant colonization. Active PGPR strain Bacillus atrophaeus UCMB-5137 was studied in this research. RNA sequencing profiles were generated in experiments where root exudate stimulations were used to mimic interactions between bacteria and plants. It was found that the gene regulation in B. atrophaeus UCMB-5137 in response to the root exudate stimuli differed from the reported gene regulation at similar conditions in B. amyloliquefaciens FZB42, which was considered as a paradigm PGPR. This difference was explained by hypersensitivity of UCMB-5137 to the root exudate stimuli impelling it to a sessile root colonization behavior through the CcpA-CodY-AbrB regulation. It was found that the transcriptional factor DegU also could play an important role in gene regulations during plant colonization. A significant stress caused by the root exudates on in vitro cultivated B. atrophaeus UCMB-5137 was noticed and discussed. Multiple cases of conflicted gene regulations showed scantiness of our knowledge on the regulatory network in Bacillus. Some of these conflicted regulations could be explained by interference of non-coding RNA (ncRNA). Search through differential expressed intergenic regions revealed 49 putative loci of ncRNA regulated by the root exudate stimuli. Possible target mRNA were predicted and a general regulatory network of B. atrophaeus UCMB-5137 genome was designed.