Journal of Clinical & Medical Genomics

Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) is correlated to reduced risk of developing cancer through reduction of inflammation, which is an important risk factor for cancer. Several studies have investigated the possible association between polymorphisms in the gene encoding inflammatory cytokines and use of NSAIDs with cancer risk; however, these studies have obtained mixed results. Therefore, we performed a meta-analysis to evaluate the association between genetic polymorphisms of Interleukin (IL) 1B, IL6, IL8, and IL10, and NSAID usage with respect to cancer risk. We conducted a comprehensive search in PubMed through May 2013. Odds Ratios (ORs) with corresponding 95% Confidence Intervals (CIs) were calculated using the fixed-effect or the random-effect model. Comprehensive search of databases revealed eight studies fulfilling the inclusion criteria. For IL6 rs1800795, the minor allele carriers demonstrated a significantly decreased cancer risk compared to those homozygous for the major allele (GG) among NSAID users (OR=0.80, 95% CI=0.68-0.95). For IL8 rs4073, NSAID users had a significantly decreased cancer risk compared to the non-NSAID users (OR=0.71, 95% CI=0.53-0.96) among those homozygous for the major allele (TT). For the IL1B rs1143627 and IL10 rs1800872 SNPs, we did not observe any significant difference. We identified a correlation between the polymorphisms IL6 rs1800795 and IL8 rs4073 and NSAID usage in decreased cancer risk.

Bacterial Artificial Chromosomes (BACs) are large extra-chromosomal plasmids in bacteria that faithfully propagate large pieces of DNA from the chromosomes of organisms. Because they represent tiny contiguous pieces of the chromosome, BACs are ideally suited for expression of genes in their chromosomal contexts. Genes in BACs can be monitored for expression after the DNA is modified with reporter genes and other sequences that allow it to be stably propagated in the new host. Several methods have been developed to alter BAC DNA within its bacterial host. One approach uses Tn10 mini-transposons to introduce exogenous DNA into BACs. The random insertions of Tn10 carrying lox sites have directed mammalian cell-selectable antibiotic resistance genes, enhancer-traps and inverted repeat ends of the vertebrate transposon Tol2 precisely to the ends of genomic DNA inserts in BACs. Reporter gene expression from BAC DNA integrated into zebrafish or mouse chromosomes have resulted from such retrofitting. The methodology has been used extensively to analyze regulation of the Amyloid Precursor Protein (appb) gene in zebrafish. Functional identification of long-range regulatory sequences of appb has provided important clues for regulation of the APP gene in humans.

The detection of a wide range of genomic alterations plays an important role in the diagnostics improving individual therapeutic approaches of cancer patients. Technologies that help to identify therapeutic relevant targets in tumor samples are a major factor on the way to a personalized medicine. The number of predictive and prognostic markers that influence the therapeutic outcome is continuously increasing. Therefore, parallel sequencing also named next generation sequencing (NGS), allowing the simultaneous analysis of numerous cancer related hotspots in many patients starting from a limited amount of DNA, is urgently needed to be established in cancer diagnostics. Different methods of target library preparation are commercially available and offer the opportunity to sequence tumor relevant hotspot mutations in a panel of genes.

In the present study, a multiplex PCR approach, targeting a lung cancer and a leukemia gene panel, each consisting of 20 disease and therapy relevant genes, was investigated. Twelve formalin fixed and paraffin embedded lung tumors and twelve native Chronic Lymphocytic Leukemia (CLL) samples, respectively, were analyzed. Samples were sequenced on the MiSeq sequencer platform.

The results showed a very high quality of each run. In spite of the low DNA input, each multiplex approach allowed a simultaneous analysis of 20 genes, in total covered by around 1,000 amplicons, in up to twelve cancer samples.

Thus, the application of NGS on amplicon targets revealed an excellent performance in detecting a wide range of genetic alterations, combined with a high sensitivity.

The myeloproliferative neoplasms are classified in four major diseases: Chronic Myeloid Leukemia, Polycythemia Vera, Primary Myelofibrosis and Essential Thrombocythemia. The JAK2 V617F mutation is found in 95% of Polycythemia Vera, and 50% of Essential Thrombocythemia and Primary Myelofibrosis patients. It was thought that the JAK2 V617F mutation and BCR-ABL1 translocation were mutually exclusive; but now a few cases have been reported with both alterations. We report a rare case with the presence of JAK2 V617F mutation, secondary to a diagnosis of BCR-ABL positive chronic myeloid leukemia. The patient was initially diagnosed as chronic myeloid leukemia and was BCR-ABL1 positive, so he started to receive Imatinib. He responded well to the therapy for three years, but after this time the patient had a hematological relapse still with no detectable copies of BCR-ABL1. For this reason, we thought of the possible development of another genetic alteration. Because the patient had a very high platelet count, we decided to look for the JAK2 V617F mutation, which result was positive. This case is just one of the few that have been reported worldwide that have a coexistence of these two genetic alterations: the BCR-ABL1 transcript and JAK2 V617F mutation in chronic myeloproliferative syndromes. This is the first case in the Central American population, found in our series of a total of 168 patients with Philadelphia positive chronic myeloid leukemia.

Background: Insulin Resistance (IR) is a condition which precedes the development of type 2 diabetes mellitus (T2DM). Resistin is a hormone secreted by adipocytes. Resistin gene (RETN) polymorphisms has been found to be associated with obesity and insulin resistance. We choose 60 patients have known type 2 diabetes mellitus against 45 healthy subjects to investigate the relationship between RETN +299 gene polymorphisms and insulin resistance, in non-obese patients with T2DM.

Results: The present study revealed statistically significant increase in AA and combined GA+AA genotypes (with ODD Ratio 4.04 and 4.75 respectively), and statistically significant decrease in GG genotype in non-obese T2DM as compared to the control subjects. Also we found statistically significant increase in A allele and serum resistin in T2DM group as compared to the control group. In addition there were statistically significant increase in mean value ± SD of fasting blood glucose, insulin, HOMA-IR, HbA1C%, Resistin, total cholesterol, triglyceride, LDL-C and statistically significant decrease in mean value ± SD in serum HDL-C in AA combined AA+GA subgroups as compared to GG subgroup of T2DM group.

Conclusions: Our study has shown that resistin +299G/A is an important genetic regulator that resulted hyperresistinemia and subsequently may be predisposing factor the development of T2DM in non-obese Egyptian population.