Role of genetic testing for inherited prostate cancer risk: Philadelphia prostate cancer consensus conference 2017

Purpose: Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-dri

Export instability and political violence in underdeveloped countries

There have been few attempts to empirically delineate and assess the importance of "external" or "international" factors in the study of comparative politics and political development. The purpose of this thesis is to examine an "international-national linkage" which has been the subject of Considerable speculation butressed with anecdotal evidence. The linkage is between the short term instability of export proceeds of underdeveloped countries and the amount of political violence with in these countries. The independent variables are export instability, export losses, export instability impact, and the impact of export losses. In the first section of the thesis, the external nature of export instability is discussed. Export instability is not always induced externally. The evidence linking export in stability to domestic economic disturbances and economic disturbances to political violence is presented and discussed in the next section. Domestic economic disturbance is an unmeasured intervening variable in this study. There are many methods of computing the instability of export proceeds. Percentage deviations from annual trend values are used in this thesis, with the trend values computed using five year moving averages. The data sources and various measures of political violence available are assessed in terms of validity and reliability. A composite index of "the total magnitude of civil strife," developed by Gurr and Ruttenberg, is used to measure the amount of political violence. The results of across-sectional correlation analysis for a sample of forty-seven underdeveloped countries indicate zero relationships between the four independent variables and political violence. A lack of covariation within the total sample may obscure significant correlations of opposite sign within specified subsamples. Accordingly, the sample is subdivided into three relatively homogeneous socio-economic regions and four political system types. The extent and direction of the relationships does vary according to region and type of political system. The variation is not large.Arts, Faculty ofPolitical Science, Department ofGraduat

Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease

Associations of prostate cancer risk variants with disease aggressiveness: results of the NCI-SPORE Genetics Working Group analysis of 18,343 cases

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤ 6, 7, ≥ 8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness