Personalized Lung Cancer Screening – Acceptability among Primary Care Providers

https://openworks.mdanderson.org/sumexp22/1065/thumbnail.jp

Polymorphisms of TGFB1 and VEGF genes and survival of patients with gastric cancer

<p>Abstract</p> <p>Background</p> <p>Some <it>TGFB1 </it>and <it>VEGF </it>polymorphisms are believed to be functional. Given that these genes are involved in tumor growth and progression including angiogenesis, dissemination, and invasiveness, we hypothesized that these polymorphisms would be associated with survival in patients with gastric cancer.</p> <p>Methods</p> <p>We genotyped <it>TGFB1 </it>-509 C>T, +1869 T>C, and +915 G>C and <it>VEGF </it>-1498T>C, -634G>C, and +936C>T in 167 patients with gastric cancer. Using the Kaplan and Meier method, log-rank tests, and Cox proportional hazard models, we evaluated associations among <it>TGFB1 </it>and <it>VEGF </it>variants with overall, 1-year, and 2-year survival rates.</p> <p>Results</p> <p>Although there were no significant differences in overall survival rates among all polymorphisms tested, patients with <it>TGFB1</it>+915CG and CC genotypes had a poorer 2-year survival (adjusted hazard ratio (HR), 3.06; 95% confidence interval (CI), 1.09–8.62; <it>P </it>= 0.034) than patients with the GG genotype had. In addition, patients heterozygous for <it>VEGF </it>-634CG also had a poorer 1-year survival (adjusted HR, 2.08; 95% CI, 1.03–4.22; <it>P </it>= 0.042) than patients with the -634GG genotype.</p> <p>Conclusion</p> <p>Our study suggested that <it>TGFB1</it>+915CG/CC and <it>VEGF </it>-634CG genotypes may be associated with short-term survival in gastric cancer patients. However, larger studies are needed to verify these findings.</p

Colorectal and Breast Cancer Screening in the U.S. during the COVID-19 Pandemic

https://openworks.mdanderson.org/sumexp21/1063/thumbnail.jp

Small sample properties of rare variant analysis methods

We are now well into the sequencing era of genetic analysis, and methods to investigate rare variants associated with disease remain in high demand. Currently, the more common rare variant analysis methods are burden tests and variance component tests. This report introduces a burden test known as the modified replication based sum statistic and evaluates its performance, and the performance of other common burden and variance component tests under the setting of a small sample size (103 total cases and controls) using the Genetic Analysis Workshop 18 simulated data with complete knowledge of the simulation model. Specifically we look at the variable threshold sum statistic, replication-based sum statistics, the C-alpha, and sequence kernel association test. Using minor allele frequency thresholds of less than 0.05, we find that the modified replication based sum statistic is competitive with all methods and that using 103 individuals leads to all methods being vastly underpowered. Much larger sample sizes are needed to confidently find truly associated genes

The VEGF -634G>C promoter polymorphism is associated with risk of gastric cancer

<p>Abstract</p> <p>Background</p> <p>Both TGF-β1 and VEGF play a critic role in the multiple-step process of tumorgenesis of gastric cancer. Single nucleotide polymorphisms (SNPs) of the <it>TGFB1 </it>and <it>VEGF </it>genes have been associated with risk and progression of many cancers. In this study, we investigated the association between potentially functional SNPs of these two genes and risk of gastric cancer in a US population.</p> <p>Methods</p> <p>The risk associated with genotypes and haplotypes of four <it>TGFB1 </it>SNPs and four <it>VEGF </it>SNPs were determined by multivariate logistic regression analysis in 171 patients with gastric cancer and 353 cancer-free controls frequency-matched by age, sex and ethnicity.</p> <p>Results</p> <p>Compared with the <it>VEGF</it>-634GG genotype, the -634CG genotype and the combined -634CG+CC genotypes were associated with a significantly elevated risk of gastric cancer (adjusted OR = 1.88, 95% CI = 1.24-2.86 and adjusted OR = 1.56, 95% CI = 1.07-2.27, respectively). However, none of other <it>TGFB1 </it>and <it>VEGF </it>SNPs was associated with risk of gastric cancer.</p> <p>Conclusion</p> <p>Our data suggested that the <it>VEGF</it>-634G>C SNP may be a marker for susceptibility to gastric cancer, and this finding needs to be validated in larger studies.</p

Comparison of two statistical methods for rare variant association analysis

Studies have shown that rare genetic variants have stronger effects in predisposing common diseases, and several statistical methods have been developed for association studies involving rare variants. In order to better understand how these statistical methods perform, we seek to compare two recently developed rare variant statistical methods (VT and C-alpha) on 10,000 simulated re-sequencing data sets with disease status and the corresponding 10,000 simulated null data sets. The SLC1A1 gene has been suggested to be associated with diastolic blood pressure (DBP) in previous studies. In the current study, we applied VT and C-alpha methods to the empirical re-sequencing data for the SLC1A1 gene from 300 whites and 200 blacks. We found that VT method obtains higher power and performs better than C-alpha method with the simulated data we used. The type I errors were well-controlled for both methods. In addition, both VT and C-alpha methods suggested no statistical evidence for the association between the SLC1A1 gene and DBP. Overall, our findings provided an important comparison of the two statistical methods for future reference and provided preliminary and pioneer findings on the association between the SLC1A1 gene and blood pressure

Molecular mechanisms of NF-κB activation in metastatic pancreatic cancer cells

Pancreatic adenocarcinoma is the fourth leading cause of adult cancer death in the United States. At the time of diagnosis, most patients with pancreatic cancer have advanced and metastatic disease, which makes most of the traditional therapeutic strategies are ineffective for pancreatic cancer. A better understanding of the molecular basis of pancreatic cancer will provide the approach to identify the new strategies for early diagnosis and treatment. NF-κB is a family of transcription factor that play important roles in immune response, cell growth, apoptosis, and tumor development. We have shown that NF-κB is constitutively activated in most human pancreatic tumor tissues and cell lines, but not in the normal tissues and HPV E6E7 gene-immortalized human pancreatic ductal epithelial cells (HPDE/E6E7). By infecting the pancreatic cancer cell line Aspc-1 with a replication defective retrovirus expressing phosphorylation-defective IκBα (IκBαM), the constitutive NF-κB activation is blocked. Subsequent injection of this Aspc-1/IκBαM cells into the pancreas of athymic nude mice showed that liver metastasis is suppressed by the blockade of NF-κB activation. Current studies showed that an autocrine mechanism accounts for the constitutive activation of NF-κB in metastatic human pancreatic cancer cell lines, but not in nonmetastatic human pancreatic cancer cell lines. Further investigation showed that interleukin-1α (IL-1α) was the primary cytokine secreted by these cells that activates NF-κB. Inhibition of IL-1α activity suppressed the constitutive activation of NF-κB and the expression of its downstream target gene, uPA, in metastatic pancreatic cancer cell lines. Even though IL-1α is one of the previously identified NF-κB downstream target genes, our results demonstrate that regulation of IL-1α expression is independent of NF-κB and primarily dependent on AP-1 activity, which is in part induced by overexpression of EGF receptors and activation of MAP kinases. In conclusion, our findings suggest a possible mechanism by which NF-κB is constitutively activated in metastatic human pancreatic cancer cells and a possible missing mechanistic links between inflammation and cancer

Genome-wide identification of genes probably relevant to the adaptation of schizothoracins (Teleostei: Cypriniformes) to the uplift of the Qinghai-Tibet Plateau

Abstract Background Molecular adaptation to the severe environments present during the uplift of the Qinghai-Tibet Plateau has attracted the attention of researchers. The divergence of the three specialization groups of schizothoracins (Primitive, Specialized and Highly Specialized) may correspond to the three phases of plateau uplift. Based on the transcripts of representative species of the three specialized groups and an outgroup, genes in schizothoracins that may have played important roles during the adaptation to new environments were investigated. Results The contigs of Gymnodiptychus dybowskii and Schizothorax pseudaksaiensis were compared with those of Gymnocypris przewalskii ganzihonensis and the outgroup Sinocyclocheilus angustiporus, and 5,894 ortholog groups with an alignment length longer than 90 nt after deleting gaps were retained. Evolutionary analyses indicated that the average evolutionary rate of the branch leading to the Specialized group was faster than that of the branch leading to the Highly Specialized group. Moreover, the numbers of gene categories in which more than half of the genes evolved faster than the average values of the genome were 117 and 15 along the branches leading to the Specialized and Highly Specialized groups, respectively. A total of 40, 36, and 55 genes were likely subject to positive selection along the branches leading to the Primitive, Specialized and Highly Specialized groups, respectively, and many of these genes are likely relevant to adaptation to the cold temperatures, low oxygen concentrations, and strong ultraviolet radiation that result from elevation. Conclusions By selecting representative species of the three groups of schizothoracins and applying next-generation sequencing technology, several candidate genes corresponding to adaptation to the three phases of plateau uplift were identified. Some of the genes identified in this report that were likely subject to positive selection are good candidates for subsequent evolutionary and functional analyses of adaptation to high altitude

The complete mitochondrial genome of Schizothorax eurystomus Kessler, 1872 (Cypriniformes, Cyprinidae)

Schizothorax eurystomus, Kessler 1872 is a unique economic fish in Xinjiang, China that is rarely seen in the market. Next-generation sequencing (NGS) was used to determine the complete mitochondrial genome of S. eurystomus collected from the Yarkand River in Xinjiang. The results showed that the mitochondrial genome is a circular, 16,488-bp-long nucleotide with the typical vertebrate genome structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. The termination-associated sequence (TAS), central conserved sequence block (CSB), and conserved sequence block were detected in the control region. Phylogenetic analysis placed S. eurystomus in a fully supported clade with S. biddulphi, and that clade was sister to S. yunnanensis. To our knowledge, this is the first study on the complete mitochondrial genome of S. eurystomus from the Yarkand River in Xinjiang, and it provides baseline genetic information for future studies

Complete mitochondrial genome of the juvenile Gymnodiptychus dybowskii (Cypriniformes, Cyprinidae, Schizothoracinae) from Ili River by high-throughput sequencing and the phylogenetic relationship of Schizothoracinae species

The complete mitochondrial genome of the juvenile Gymnodiptychus dybowskii collected from Ili River was determined by high-throughput sequencing. The mitogenome is a circular molecule 16,657bp in length, including 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a control region. The TAS, central CSB and CSB were detected in the control region. The gene contents of the mitogenome are identical to those observed in most bony fishes. The NJ phylogenetic tree showed that G. dybowskii clustered into one branch with the species from the same genus