Evaluation Of Single Nucleotide Polymorphisms Research Articles

Evaluation of Single Nucleotide Polymorphisms (SNPs) Associated with Genetic Resistance to Bovine Paratuberculosis in Marchigiana Beef Cattle, an Italian Native Breed.

Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of paratuberculosis (PTB), a widespread chronic enteritis of ruminants. The progression of the infection depends on the containment action of innate and cell-mediated immunity (CMI), and it is related to environmental and genetic factors. In particular, PTB susceptibility seems to be associated with specific genes coding for immune regulators involved in the cell-mediated response during the infection. The aim of this preliminary study was to verify, in Italian beef cattle, an association between MAP infectious status and the presence of single nucleotide polymorphisms (SNPs) in candidate genes. To the best of our knowledge, this is the first investigation conducted on a native beef cattle breed, known as Marchigiana, reared in Central Italy. The present research, based on a longitudinal study, aimed to identify and correlate phenotypic and genetic profiles characteristic of the subjects potentially able to contrast or contain PTB. In a MAP-infected herd, ELISA, IFN-γ tests, qPCR, and cultures were performed at a follow-up, occurring within a period ranging from three to six years, to evaluate the individual state of infection. Animals testing positive for at least one test were considered infected. DNA samples of 112 bovines, with known MAP statuses, were analyzed to verify an association with SNPs in the genes encoding gamma-interferon (BoIFNG), interleukin receptor 10 (IL10RA), interleukin receptor 12 (IL12RB2), and toll-like receptors (TLR1, TLR2, TLR4). Regarding statistical analysis, the differences among target genes and pairs of alleles in the analyzed groups of animals, were evaluated at a significance level of p < 0.05. For IL10RA and for IL12RB2 genes, relevant differences in genotypic frequencies among the considered cattle groups were observed. For all candidate genes studied in this investigation, SNP genotypes already associated with PTB resistance were found more frequently in our population, suggesting potential resistance traits in the Marchigiana breed.

Evaluation of Single-Nucleotide Polymorphisms in Human Serum Albumin Associated with Alzheimer's Disease

Human serum albumin (HSA) is a natural buffer for amyloid в peptide (Аβ), which is a key factor in the development of Alzheimer's disease (AD). An increase in HSA affinity to Аβ can be achieved via HSA saturation with low-molecular-weight ligands, such as serotonin or specific fatty acids. The conducted analysis of the genomic data of exomes (WES) associated with AD (ADSP database) revealed the presence of a single-nucleotide polymorphism of the HSA gene at the binding sites of ibuprofen, arachidonic and oleic acids. Research into the properties of the revealed genetic variants of HSA should be carried out to determine those variants that are susceptible to the modulatory action of HSA ligands, thus increasing its affinity to Aβ.

Evaluation of Single Nucleotide Polymorphism and Genetic Diversity at the Myostatin gene Locus in Indigenous and Locally Adapted Exotic Turkey breeds in Nigeria

This research was carried out to characterize single nucleotide polymorphism at the myostatin gene locus in indigenous and Nigerian locally adapted exotic turkeys. A total of 220-day-old poults comprising 120 local and 100 locally adapted exotic turkeys were sourced from reputable hatchery and were managed for 20 weeks under intensive management system. Blood samples were collected from 70 turkeys each form the two breeds via the brachial vein into Ethylene Diamine Tetra Acetic Acid (EDTA) bottles for DNA extraction and amplification of target regions using commercially available kits when the birds were 8 weeks. Genomic regions containing exon 1 and 2 of MSTN gene including their surrounding introns were sequenced and analyzed using BioEdit, Codon Code Aligner, DnaSP and MEGA software. Codon-based test was also performed to estimate the ratio of non-synonymous substitutions (dN) to synonymous substitutions (dS). Results from our study showed that both local and exotic turkey breeds had one non-synonymous single nucleotide polymorphism (SNP) (248 G&gt;A) in exon 1 while SNP variant 333 G&gt;A was detected only in exon 2 of exotic turkey. In intron 1, a total of 3 SNPs in local turkey and 2 SNPs in exotic turkey were detected. Intron 2 also revealed 4 and 3 SNPs in local and exotic turkeys respectively. Genetic diversity indices showed that local turkey had higher haplotype diversity at intron 1 (75 %) and intron 2 (84 %) while haplotype diversity of 20 % was estimated at exon 2 in exotic turkey. Our Codon-based test of selection showed dN/dS ratio of &lt;1 (purifying selection) at G248A SNP loci, suggested a possible role of this non-synonymous SNP variant on growth performance. We recommend a population-based study to investigate the effect of this non-synonymous SNP G248A on growth and morpho-structural traits for breed improvement and conservation of our locally adapted turkey populations.

Mitigation of nontuberculous mycobacteria in hospital water: challenges for infection prevention.

The purpose of this review is to summarize recent literature on nontuberculous mycobacteria in water of healthcare systems. Despite improvement in identification techniques and emergence of infection prevention and control programs, nontuberculous mycobacteria remain present in hospital water systems, causing outbreaks and pseudo-outbreaks in healthcare settings. Waterborne outbreaks and pseudo-outbreaks of nontuberculous mycobacteria continue to affect hospitals. Improvements in methods of identification and investigation, including MALDI-TOF and whole genome sequencing with evaluation of single nucleotide polymorphisms, have been used successfully in outbreak and pseudo-outbreak investigations. Recent studies have shown control of outbreaks in immunocompromised patients through the use of sterile water for consumption, as well as control of pseudo-outbreaks by using sterile water for procedures. Construction activities have been implicated in outbreaks and pseudo-outbreaks of nontuberculous mycobacteria. Water management programs are now required by the Joint Commission, which will likely improve water risk mitigation. Improvement in detection and identification of nontuberculous mycobacteria has led to increasing recognition of waterborne outbreaks and pseudo-outbreaks. Water management programs are of vital importance in infection prevention.

Evaluation of single nucleotide polymorphisms identified through the use of SNP assay in Romanian and Chinese Holstein and Simmental cattle breeds.

Simmental and Holstein cattle, being among the most widely distributed breeds worldwide, have been subjected to continuous selection for distinct purposes. In the current study, we evaluated the levels of SNPs identified through the use of SNP assay in Romanian Holstein and Romanian Simmental cattle, which then were compared to the data from Chinese Holstein and Chinese Simmental cattle. In total, 282 animals were genotyped: Romanian Holstein (n=30), Romanian Simmental (n=22), Chinese Holstein (n=96) and Chinese Simmental cattle (n=136), using 39,724 common SNPs to analyze minor allele frequency, genetic variability and level of SNPs. Among studied breeds, the average percentage of polymorphic markers was 90.84%, with the highest value in Chinese Simmental (91.37%) and lowest in Romanian Simmental cattle (90.31%). The average HO ranged from 0.426 in Romanian Holstein to 0.416 in Romanian Simmental, and from 0.425 in Chinese Holstein to 0.422 in Chinese Simmental. The distribution of SNPs was homogenous across the breeds, except the Romanian Simmental which displayed the lowest percentage of polymorphic markers (24,66 and 32,48%) from higher MAF category (0.3 to <0.4 and 0.4 to <0.5) and the highest percentage (3.82 and 12.00%) for SNPs from low and intermediate MAF categories (0.05 to <0.1 and 0.1 to <0.2). In the current study, the SNP assay was successfully used to analyze the level of SNP sites of Romanian cattle breeds, however, a higher number of samples and production data are needed for future applications of the results in genomic selection, genome-wide association studies and genetic diversity analysis.

Population genomic transformations induced by isolation of wild bird avian influenza viruses (Orthomyxoviridae) in embryonated chicken eggs.

Isolation and cultivation of wild-type viruses in model organism cells or tissues is standard practice in virology. Oftentimes, the virus host species is distantly related to the species from which the culture system was developed. Thus, virus culture in these tissues and cells basically constitutes a host jump, which can lead to genomic changes through genetic drift and/or adaptation to the culture system. We directly sequenced 70 avian influenza virus (Orthomyxoviridae) genomes from oropharyngeal/cloacal swabs collected from wild bird species and paired virus isolates propagated from the same samples following isolation in specific-pathogen-free embryonated chicken eggs. The data were analyzed using population genetic approaches including evaluation of single nucleotide polymorphism (SNP) frequencies and divergence with pooled-sequencing analyses, consensus sequence placement in neighbor-joining trees, and haplotype reconstruction and networks. We found that propagation of virus in eggs leads to skewed SNP mutation spectra with some SNPs going to fixation. Both synonymous and nonsynonmous SNP frequencies shifted. We found multiple consensus sequences that differed between the swabs and the isolates, with some sequences from the same sample falling into divergent genetic clusters. Twenty of 23 coinfections detected had different dominant subtypes following virus isolation, thus sequences from both the swab and isolate were needed to obtain full subtype data. Haplotype networks revealed haplotype frequency shifts and the appearance or loss of low-frequency haplotypes following isolation. The results from this study revealed that isolation of wild bird avian influenza viruses in chicken eggs leads to skewed populations that are different than the input populations. Consensus sequence changes from virus isolation can lead to flawed phylogenetic inferences, and subtype detection is biased. These results suggest that for genomic studies of wild bird influenza viruses the biological field should move away from chicken egg isolation towards directly sequencing the virus from host samples.

A comprehensive evaluation of single nucleotide polymorphisms associated with atrophic gastritis risk: A protocol for systematic review and network meta-analysis.

Single nucleotide polymorphisms (SNPs) have been inconsistently associated with atrophic gastritis (AG) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with AG. To identify all associated studies of SNPs and AG published, databases had been searched through January 2020 from the databases of PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, Embase, the Chinese Science and Technology Periodical Database (VIP), Cochrane Library, and Wanfang databases. With the help of network meta-analysis and Thakkinstian algorithm, the best genetic model with the strongest correlation with AG was selected, the final result - matching to the noteworthy correlation - was obtained by referring to the false positive reporting rate (false positive report probability, FPRP). Based on STREGA's stated criteria, the methodological quality of the data we collected was valued. Both Stata 14.0 and GeMTC will be used for a comprehensive review of the system and will be used in our meta-analysis. This study will provide a high-quality evidence to find the SNP most associated with AG susceptibility and the best genetic model. This study will explore which SNP is most associated with AG susceptibility. INPLASY202050016.

A comprehensive evaluation of single nucleotide polymorphisms associated with osteosarcoma risk: A protocol for systematic review and network meta-analysis.

Single nucleotide polymorphisms (SNPs) have been inconsistently associated with osteosarcoma (OS) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with OS. Databases were searched to identify association studies of SNPs and OS published through January 2020 from the databases of PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, and Wan fang databases. Network meta-analysis and Thakkinstian algorithm were used to select the most appropriate genetic model, along with false positive report probability for noteworthy associations. The methodological quality of data was assessed based on the STrengthening the REporting of Genetic Association Studies statement Stata 14.0 will be used for systematic review and meta-analysis. This study will provide a high-quality evidence to find the SNP most associated with OS susceptibility and the best genetic model. This study will explore which SNP is most associated with OS susceptibility. INPLASY202040023.

A comprehensive evaluation of single nucleotide polymorphisms associated with gastric cancer risk: A protocol for systematic review and network meta-analysis.

Single nucleotide polymorphisms (SNPs) have been inconsistently associated with gastric cancer (GC) risk. This meta-analysis aimed to synthesize relevant data on SNPs associated with GC. Databases were searched to identify association studies of SNPs and GC published through January 2020 from the databases of PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, and Wan fang databases. Network meta-analysis and Thakkinstian algorithm were used to select the most appropriate genetic model, along with false positive report probability for noteworthy associations. The methodological quality of data was assessed based on the STrengthening the REporting of Genetic Association Studies statement Stata 14.0 will be used for systematic review and meta-analysis. This study will provide a high-quality evidence to find the SNP most associated with GC susceptibility and the best genetic model. This study will explore which SNP is most associated with GC susceptibility. INPLASY202040132.

Investigation of type 1 diabetes in NOD mice knockout for the osteopontin gene.

Type 1 diabetes onset is preceded by a pre-inflammatory stage leading to insulitis and followed by targeted destruction of the insulin-producing beta cells of the pancreas. Osteopontin (OPN) is a secreted phosphoprotein with cytokine properties, implicated in many physiological and pathological processes, including infection and autoimmunity. We have previously identified up-regulated osteopontin transcripts in the pancreatic lymph nodes of the NOD (Non-Obese Diabetic) mouse at the pre-diabetic stages. Investigating the underlined disease initiating mechanisms may well contribute to the development of novel preventive therapies. Our aim was to construct opn null mice in a NOD autoimmune-prone genetic background and address the pathogenic or protective role of the osteopontin molecule in the early stages of type 1 diabetes. We generated opn null mutant mice in a NOD genetic background by serial backcrossing to the existing C57BL/6 opn knockout strain. The presence of opn wild type or null alleles in the congenic lines was evaluated by PCR amplification. We used NOD opn-null mice to assess the phenotypic evolution of type 1 diabetes. The presence of OPN in the serum was evaluated by ELISA and by immunostaining on the mouse tissues. The primary gene structure of the NOD opn encoding gene and protein sequences were compared to the known alleles of other mouse strains. Evaluation of Single Nucleotide Polymorphisms (SNPs) variation between opn alleles of the opn gene is reported. In the absence of OPN, type 1 diabetes is accelerated, suggesting a protective role of this cytokine on the insulin-producing cells of the pancreatic islets. Conversely, in the presence of the opn gene, an increase of the OPN protein in the serum of young NOD mice indicates that this molecule might be involved in the immune regulatory events taking place at early stages, prior to disease onset. Our data support that OPN acts as a positive regulator of the early islet autoimmune damage, possibly by a shift of the steady-state of T1D pathogenesis. We report that the OPN protein structure of the NOD/ShiLtJ strain corresponds to the a-type allele of the osteopontin gene. Comparative analysis of the single nucleotide polymorphisms between the a-type and b-type alleles indicates that the majority of variations are within the non-coding regions of the gene. The construction of opn null mice in an autoimmune genetic background (NOD.B6.Cg-spp1-/-) provides important tools for the study of the implication of the OPN in type 1 diabetes, offering the possibility to address the significance of this molecule as an early marker of the disease and as a therapeutic agent in preclinical studies.

Evaluation of single nucleotide polymorphisms in 6 candidate genes and carotid intima-media thickness in community-dwelling residents.

Evidence suggests the existence of association between a large panel of modifiable biomarkers representing inflammation, coagulation, paraoxonase, and endothelial activation pathways and carotid atherosclerosis. Thus, this study investigated whether CRP, FGA, FGB, FGG, PON1, and EDNRA gene variants affected plasma hs-CRP, fibrinogen levels, and thickness of carotid intima media thickness (IMT). Nineteen single-nucleotide polymorphisms of CRP, FGA, FGB, FGG, PON1, and EDNRA genes were examined in 480 participants from 160 families. Carotid IMT was measured by ultrasound. Generalized linear models with generalized estimating equation were utilized to consider the dependence of subjects within families. In the recessive model, homozygotes for the minor alleles of rs1800789, rs1800790 and rs4220 SNPs in FGB gene indicated a reduced risk of IMT (Exp. β = 0.89, 0.89, 0.88), which remained significant after adjustment for confounding factors. Significant interaction effects between CRP SNP rs1130864 and rs3093059 and gender for IMT were observed with a significant association in men only. Men carrying minor-minor genotype of CRP SNP rs1130864 and rs3093059 had 0.70- and 0.78-fold lower IMT than men carrying minor-major/major-major genotype. We also observed that the interaction of CRP SNP rs1130864 and rs3093059 with obesity on IMT, hs-CRP and fibrinogen levels. These results support the hypothesis that inflammatory genes are involved in atherosclerosis, most likely via complex gene-gender and gene-obesity interactions.

Two Phages of the Genera Felixounavirus Subjected to 12 Hour Challenge on Salmonella Infantis Showed Distinct Genotypic and Phenotypic Changes.

Salmonella Infantis is considered in recent years an emerging Salmonella serovar, as it has been associated with several outbreaks and multidrug resistance phenotypes. Phages appear as a possible alternative strategy to control Salmonella Infantis (SI). The aims of this work were to characterize two phages of the Felixounavirus genus, isolated using the same strain of SI, and to expose them to interact in challenge assays to identify genetic and phenotypic changes generated from these interactions. These two phages have a shared nucleotide identity of 97% and are differentiated by their host range: one phage has a wide host range (lysing 14 serovars), and the other has a narrow host range (lysing 6 serovars). During the 12 h challenge we compared: (1) optical density of SI, (2) proportion of SI survivors from phage-infected cultures, and (3) phage titer. Isolates obtained through the assays were evaluated by efficiency of plating (EOP) and by host-range characterization. Genomic modifications were characterized by evaluation of single nucleotide polymorphisms (SNPs). The optical density (600 nm) of phage-infected SI decreased, as compared to the uninfected control, by an average of 0.7 for SI infected with the wide-host-range (WHR) phage and by 0.3 for SI infected with the narrow-host-range (NHR) phage. WHR phage reached higher phage titer (7 × 1011 PFU/mL), and a lower proportion of SI survivor was obtained from the challenge assay. In SI that interacted with phages, we identified SNPs in two genes (rfaK and rfaB), which are both involved in lipopolysaccharide (LPS) polymerization. Therefore, mutations that could impact potential phage receptors on the host surface were selected by lytic phage exposure. This work demonstrates that the interaction of Salmonella phages (WHR and NHR) with SI for 12 h in vitro leads to emergence of new phenotypic and genotypic traits in both phage and host. This information is crucial for the rational design of phage-based control strategies.

Evaluation of single nucleotide polymorphism in interleukin 22 (IL-22) gene and its association with chronic hepatitis B infection.

This study aimed to evaluate rs1179251 single nucleotide polymorphism in the IL-22 gene as a host factor and its effect on chronic hepatitis B infection. Interleukin 22 (IL-22) belongs to a group of recently discovered cytokines, and it is produced and secreted by innate lymphoid cells (ILCs) and T helper 22 (Th22) cells. This cytokine plays dual roles as pro-inflammatory and anti-inflammatory effects in various conditions and different tissues of the body. This study was performed based on a case-control format to assess IL-22 rs1179251 single nucleotide polymorphism genotypic and allelic frequencies among 227 hepatitis B chronic patients and 227 healthy controls. The polymerase chain reaction and restriction fragment length polymorphism techniques were employed to determine the polymorphism's genotypes. Genotypes Frequencies in patients' group were determined CC 59.91%, CG 37.89%, and GG 2.20% respectively in comparison to CC 63.44%, CG 31.72% and GG 4.85% in control group. The findings revealed that there was no statistically significant difference in the genotypes (P=0.156) frequencies of IL-22 gene polymorphism (rs1179251) between patients and control groups. No association was found between rs1179251 single nucleotide polymorphism in IL-22 gene and chronic hepatitis B infection. So, in spite of the importance of IL-22 gene in immune responses, the studied polymorphism does not serve a decisive role in susceptibility to hepatitis B virus chronic infection.

Abstract PL04-02: Pharmacogenomics of chemotherapeutic-induced toxicities: Challenges and opportunities

Abstract PL04-02: Pharmacogenomics of chemotherapeutic-induced toxicities: Challenges and opportunities

Cytochrome c oxidase subunit 1 gene as a DNA barcode for discriminating Trypanosoma cruzi DTUs and closely related species

BackgroundThe DNA barcoding system using the cytochrome c oxidase subunit 1 mitochondrial gene (cox1 or COI) is highly efficient for discriminating vertebrate and invertebrate species. In the present study, we examined the suitability of cox1 as a marker for Trypanosoma cruzi identification from other closely related species. Additionally, we combined the sequences of cox1 and the nuclear gene glucose-6-phosphate isomerase (GPI) to evaluate the occurrence of mitochondrial introgression and the presence of hybrid genotypes.MethodsSixty-two isolates of Trypanosoma spp. obtained from five of the six Brazilian biomes (Amazon Forest, Atlantic Forest, Caatinga, Cerrado and Pantanal) were sequenced for cox1 and GPI gene fragments. Phylogenetic trees were reconstructed using neighbor-joining, maximum likelihood, parsimony and Bayesian inference methods. Molecular species delimitation was evaluated through pairwise intraspecific and interspecific distances, Automatic Barcode Gap Discovery, single-rate Poisson Tree Processes and multi-rate Poisson Tree Processes.ResultsBoth cox1 and GPI genes recognized and differentiated T. cruzi, Trypanosoma cruzi marinkellei, Trypanosoma dionisii and Trypanosoma rangeli. Cox1 discriminated Tcbat, TcI, TcII, TcIII and TcIV. Additionally, TcV and TcVI were identified as a single group. Cox1 also demonstrated diversity in the discrete typing units (DTUs) TcI, TcII and TcIII and in T. c. marinkellei and T. rangeli. Cox1 and GPI demonstrated TcI and TcII as the most genetically distant branches, and the position of the other T. cruzi DTUs differed according to the molecular marker. The tree reconstructed with concatenated cox1 and GPI sequences confirmed the separation of the subgenus Trypanosoma (Schizotrypanum) sp. and the T. cruzi DTUs TcI, TcII, TcIII and TcIV. The evaluation of single nucleotide polymorphisms (SNPs) was informative for DTU differentiation using both genes. In the cox1 analysis, one SNP differentiated heterozygous hybrids from TcIV sequences. In the GPI analysis one SNP discriminated Tcbat from TcI, while another SNP distinguished TcI from TcIII.ConclusionsDNA barcoding using the cox1 gene is a reliable tool to distinguish T. cruzi from T. c. marinkellei, T. dionisii and T. rangeli and identify the main T. cruzi genotypes.

Evaluation of Single Nucleotide Polymorphisms of Angiotensin II Type 2 Receptor (AGTR2) Gene and Interleukin 4 (IL-4) gene for the Contribution to the Risk of Preeclampsia in Turkish Population

Amaç: Preeklampsi, tüm gebeliklerin yaklaşık %6-10’ unda görülen ve gebe kadınlara özgü ciddi bir hastalıktır. İmmün ve genetik faktörlerin de katkıda bulunduğu kompleks bir hastalıktır. Bu çalışmada amacımız, AGTR2A1675G ve IL4 -590 (C>T) polimorfizmleri ve preeklampsi arasında bir ilişki olup olmadığını incelemekti. Gereç ve Yöntem: Yüz otuzbir preeklampsili ve 86 normal gebe kadından alınan periferik kandan, genomic DNA izole edildi. AGTR2 ve IL-4 polimorfizmleri polimeraz zincir reaksiyonu kullanılarak genotiplendirildi. Bulgular: AGTR2 geni 1675 polimorfizminin genotip frekansı açısından önemli bir fark bulunamadı fakat allel frekansları açısından önemli bir fark bulunmuştur. IL-4 geni -590 polimorfizmi genotip ve allel frekansları açısından önemli bir fark bulunamamıştır. Sonuç: AGTR2, GG genotipi ve IL-4, TT genotipi preeklampsili kadınlarda normal gebe kadınlara oranla önemli derecede yüksek bulundu. Bu genotipe sahip olma, preeklampsi meydana gelmesi açısından bir risk faktörü olabilir ancak bu bulgular daha fazla örnekte test edilmeye ihtiyaç duymaktadır.

SNP-E: A New Method For Multiple Sequence Alignments Analysis And Accurate Single Nucleotide Polymorphism Evaluation

Identification of single nucleotide polymorphisms (SNPs) and insertion-deletion mutations are important for discovering the connection between the genetic mutations and complex diseases. The objective of this study was to develop a sensitive and accurate computational method for SNP detection among Multiple Sequence Alignments (MSAs) to be run on Microsoft Office SuiteTM and WindowsTM. The SNP-Evaluator, was designed to simulate the process of human eye visual change-identification. Analysis of three 82-Kbp genomic loci derived from Sanger sequencing and the corresponding SNPs from 31 genomes from IlluminaTM sequencing of soybean (Glycine max L. Merr.) demonstrated that the SNP-E was an effective method for medium-scale genomic research.

Promoting Cancer Control in Africa With “Ubuntu”: A Report of the African Organization for Research and Training in Africa (AORTIC) 10th Conference, 2015 in Marrakech, Morocco

The objectives of the African Organization for Research and Training in Cancer (AORTIC), includes bringing products of decades of advances in cancer research to African populations through local and international collaboration. The consistent and huge growth in participation in the conferences and the diversity of the nations is a witness to the success of the organization thus far. The theme for the Tenth AORTIC International Conference on Cancer in Africa in Morocco in 2015 was "Road map to Cancer Control in Africa" and topics of discussion of paramount importance for low- and middle-income African countries included childhood cancers such as BL, cancers of the cervix, breast, and prostate; cancers associated with HIV-infection such as cervical, vulvar, and anal; as well as cancer care challenges associated with palliative care. The role of environmental factors that underlie some epigenetic changes in some of the cancers was emphasized. Oral and poster presentations from various parts of the continent indicate the growth of basic and translational science of cancer in the region, with studies revealing regional diversity in the frequencies of the triple-negative breast cancer, cervical cancer, prostate cancer, HCC, and Burkitt's lymphoma. There was a sign that Africa is trying to keep pace with the paradigm shift and focusing on translational medicine. This was shown by suggestions for application of genome-wide association studies, new generation sequencing, as well as the evaluation of single nucleotide polymorphisms that may be responsible for variable susceptibility in some of the prevalent cancers in people of African descent. J. Cell. Physiol. 232: 2287-2295, 2017. © 2016 Wiley Periodicals, Inc.

Polymorphisms of Genes Encoding Multidrug Resistance Proteins as a Predictive Factor for Second-Line Docetaxel Therapy in Advanced Non-small Cell Lung Cancer

Multidrug resistance (MDR) remains a substantial problem in chemotherapy. The purpose of the study was to investigate potential factors, including MDR genes polymorphisms, that could be used in qualification for second-line docetaxel therapy in non-small cell lung cancer (NSCLC) patients after failure of platinum based chemotherapy. Study group comprised of 58 Caucasian subjects. Evaluation of Single Nucleotide Polymorphisms (SNPs) of ABCC2/MRP2 and ABCB1/MDR1 genes was performed using the High Resolution Melting (HRM) technique. TUBB3 gene expression was evaluated on RNA isolated from tumor tissue. Results with p value of <0.05 were considered significant. Factors associated with reduced risk of disease progression included good performance status (PS), long period between diagnosis and docetaxel treatment, and smoking for <10 pack-years. Disease control occurred more often in patients with G/G genotype of the ABCC2/MRP2 gene. Median overall survival was 4.25 months. Factors such as: good PS, disease control after docetaxel, long period from diagnosis to docetaxel, lack of significant weight loss, and third-line treatment were associated with prolongation of patients survival. Overall survival probability was significantly lower in patients with significant weight loss, poor PS, lack of disease control after docetaxel, and without third-line treatment. Factors that characterized the highest risk of survival shortening were: inability to apply third-line treatment, lack of best response to first-line therapy, poor PS, and C/G or G/G genotypes of ABCC2/MRP2 gene. We concluded that assessed factors had mainly prognostic and not predictive value. Finding reliable molecular predictors for second line docetaxel therapy requires further clinical trials.

D23 - Pharmacogenomic evaluation of single nucleotide polymorphisms associated with oxaliplatin-induced peripheral neuropathy: a preliminary study

D23 - Pharmacogenomic evaluation of single nucleotide polymorphisms associated with oxaliplatin-induced peripheral neuropathy: a preliminary study