Posts Tagged ‘gens’

Statistical Approach for Calculating Environmental Influences in Genome-Wide Association Study (GWAS) Results

The approach fills a gap in current analyses. Complex diseases like cancer usually arise from complex interactions among genetic and environmental factors. When many such combinations are studied, identifying the relevant interactions versus those that reflect chance combinations among affected individuals becomes difficult. In this study, the investigators developed a novel approach for evaluating the relevance of interactions using a Bayesian hierarchal mixture framework. The approach is applicable for the study of interactions among genes or between genetic and environmental factors.

Chris Amos, PhD, senior author of the paper said, “These findings can be used to develop models that include only those interactions that are relevant to disease causation, allowing the researcher to remove false positive findings that plague modern research when many dozens of factors and their interactions are suggested to play a role in causing complex diseases.”

The model evaluates “gene by gene” and “gene by environment” factors by looking at specific DNA sequencing variations. Complex diseases are caused by multiple factors. In some cases a genetic predisposition or abnormality may be a factor. A person’s healthy lifestyle and environment, however, may help him or her overcome a genetic vulnerability and avoid a chronic disease like cancer. In other situations, a person whose DNA does not have an abnormality may develop one when exposed to known carcinogens like tobacco smoke or sunburn.

“Understanding the combinations of genetic and environmental factors that cause complex diseases is important,” said Amos, associate director of population sciences and deputy director of Norris Cotton Cancer Center, “because understanding the genetic architecture underlying complex disease may help us to identify specific targets for prevention or therapy upon which interventions may appropriately reduce the risk of cancer development or progression.”

The study applied the model in cutaneous melanoma and lung cancer genetic sequences using previously identified abnormalities (known as single nucleotide polymorphisms or SNPs) with environmental factors introduced as independent variables. The Bayesian mixture model was compared with the traditional logistic regression model. The hierarchal model successfully controlled the probability of false positive discovery and identified significant interactions. It also showed good performance on parameter estimation and variable selection. The model cannot be applied to a complete GWAS because if its reliance on other probability models (MCMC ). It is most effective when applied to a group of SNPs.

“The method was effective for the study of melanoma and lung cancer risk because these cancers develop from a complex interaction between genetic and environmental factors but understanding how these factors interact has been difficult to achieve without the sophisticated modeling that has been developed in this study,” said Amos.

source : http://www.sciencedaily.com/releases/2014/08/140827111811.htm

Change in circulating tumor cells detection has potential in prediction of prostate cancer

"The research of the circulating tumour cells (CTC) is of utmost importance, because nowadays there is no reliable marker of both cancer-specific or overall survival in castration-resistant prostate cancer (CRPC) patients," explained the lead author of the study, Dr. Otakar Čapoun, of the Department of Urology at General Teaching Hospital Charles University in Prague, Czech Republic.

"The goal of this study is to assess the possibility of the individualisation of castration-resistant prostate cancer management. In cases with no favourable change in CTC detection during chemotherapy, the early switching to another therapy should be considered," commented Čapoun on the implications of the study, which was supported by the Internal Grant Agency of the Ministry of Health of the Czech Republic.

Protocol of the grant project included the collection of peripheral blood from patients with metastatic CRPC prior to docetaxel therapy and after the fourth cycle of chemotherapy (CTX). Circulating tumour cells were detected by using a method of immunomagnetic separation. In the course of the study multiplex-PCR was performed after cytolysis of CTC and the expression of tumour-associated antigens (PSA, PSMA and EGFR) was quantified.

The methodology of the study was based on verbal evaluation together with a report of the absolute values (ng/ml). The authors recorded the levels of serum PSA (sPSA) and the fragments of respective antigens before and in the course of CTX and compared the values. They also evaluated the correlation between the change of sPSA and expression of CTC antigens during CTX.

The study included 26 patients with both samples taken in 17 of them. Median age was 72 years (54-82), mean sPSA level before and after CTX was 197.6 and 120.1ng/ml, respectively. Before CTX only 2 out of 26 patients were considered CTC negative, whereas during the CTX the CTC negativity was confirmed in 9 out of 17 cases. Before CTX, positive detection of fragments of antigens for PSA, PSMA and EGFR was confirmed in 23, 16 and 2 patients, respectively, and during CTX in 8, 3 and 1 case, respectively. The sPSA level before CTX was associated with the level of fragments for PSA (p=0.0020) and PSMA (p=00.0147). During CTX the association was seen in all antigens. However neither a change in sPSA level nor a change in positive versus negative CTC statement correlated with a change of any of the tested antigens.

The study concludes that the sPSA level has the most accurate correlation with the level of gene fragment for PSA in CTC. A favourable change in CTC quantity will occur in more than a half of patients during chemotherapy, however the change in CTC detection does not correlate with the change of the sPSA level.

"This research project is divided into several arms, among others, we are investigating the feasibility of CTC cultivation and genetic profiling," commented Čapoun referring to the possibility of follow-up research.

"This gene profile will be compared with primary tumour at the time of diagnosis. In the future, this CTC profiling might be useful for even more accurate and better tailored selection of treatment for castration-resistant prostate cancer."

source : http://www.sciencedaily.com/releases/2013/10/131011135228.htm