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 conserved poly(ADP-ribosyl)ation (PAR) pathway consists of three genetic components that are potential targets to modulate the plant’s energy homeostasis upon stress with the aim to improve yield stability in crops and help secure food supply. We studied the role of the PAR pathway component ADP-ribose/NADH pyrophosphohydrolase (AtNUDX7) in yield and mild drought stress by using a transgenic approach in Arabidopsis thaliana and maize (Zea mays). Arabidopsis AtNUDX7 cDNA was overexpressed in Arabidopsis and maize by means of the constitutive Cauliflower Mosaic Virus 35S promoter and the strong constitutive Brachypodium distachyon pBdEF1α promoter, respectively. Overexpression of AtNUDX7 in Arabidopsis improved seed parameters that were measured by a novel, automated method, accelerated flowering and reduced inflorescence height. This combination of beneficial traits suggested that AtNUDX7 overexpression in Arabidopsis might enhance the ADP-ribose recycling step and maintain energy levels by supplying an ATP source in the poly(ADP-ribosyl)ation energy homeostasis pathway. Arabidopsis and maize lines with high, medium and low overexpression levels of the AtNUDX7 gene were analysed in automated platforms and the inhibition of several growth parameters was determined under mild drought stress conditions. The data showed that the constitutive overexpression of the Arabidopsis AtNUDX7 gene in Arabidopsis and maize at varying levels did not improve tolerance to mild drought stress, but knocking down AtNUDX7 expression did, however at the expense of general growth under normal conditions.
This book contains the abstracts of the papers/posters presented at the Tanzania Health Summit 2020 (THS-2020) Organized by the Ministry of Health Community Development, Gender, Elderly and Children (MoHCDGEC); President Office Regional Administration and Local Government (PORALG); Ministry of Health, Social Welfare, Elderly, Gender, and Children Zanzibar; Association of Private Health Facilities in Tanzania (APHFTA); National Muslim Council of Tanzania (BAKWATA); Christian Social Services Commission (CSSC); & Tindwa Medical and Health Services (TMHS) held on 25–26 November 2020. The Tanzania Health Summit is the annual largest healthcare platform in Tanzania that attracts more than 1000 participants, national and international experts, from policymakers, health researchers, public health professionals, health insurers, medical doctors, nurses, pharmacists, private health investors, supply chain experts, and the civil society. During the three-day summit, stakeholders and decision-makers from every field in healthcare work together to find solutions to the country’s and regional health challenges and set the agenda for a healthier future.
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.
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