Posts Tagged ‘norris’

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.

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Nanoparticle ‘alarm clock’ tested to awaken immune systems put to sleep by cancer

One pioneering approach, discussed in a review article published this week in WIRE’s Nanomedicine and Nanobiotechnology, uses nanoparticles to jumpstart the body’s ability to fight tumors. Nanoparticles are too small to imagine. One billion could fit on the head of a pin. This makes them stealthy enough to penetrate cancer cells with therapeutic agents such as antibodies, drugs, vaccine type viruses, or even metallic particles. Though small, nanoparticles can pack large payloads of a variety of agents that have different effects that activate and strengthen the body’s immune system response against tumors.

There is an expanding array of nanoparticle types being developed and tested for cancer therapy. They are primarily being used to package and deliver the current generation of cancer cell killing drugs and progress is being made in that effort.

“ Our lab’s approach differs from most in that we use nanoparticles to stimulate the immune system to attack tumors and there are a variety of potential ways that can be done,” said Steve Fiering, PhD, Norris Cotton Cancer Center researcher and professor of Microbiology and Immunology, and of Genetics at the Geisel School of Medicine at Dartmouth. “Perhaps the most exciting potential of nanoparticles is that although very small, they can combine multiple therapeutic agents.”

The immune therapy methods limit a tumor’s ability to trick the immune system. It helps it to recognize the threat and equip it to effectively attack the tumor with more “soldier” cells. These approaches are still early in development in the laboratory or clinical trials.

“Now that efforts to stimulate anti-tumor immune responses are moving from the lab to the clinic, the potential for nanoparticles to be utilized to improve an immune-based therapy approach is attracting a lot of attention from both scientists and clinicians. And clinical usage does not appear too distant,” said Fiering.

Fiering is testing the use of heat in combination with nanoparticles. An inactive metallic nanoparticle containing iron, silver, or gold is absorbed by a cancer cell. Then the nanoparticle is activated using magnetic energy, infrared light, or radio waves. The interaction creates heat that kills cancer cells. The heat, when precisely applied, can prompt the immune system to kill cancer cells that have not been heated. The key to this approach is minimizing healthy tissue damage while maximizing cancerous tumor destruction of the sort that improves recognition of the tumor by the immune system.

Fiering cautions that there is a great deal of research and many technical variables that should be explored to find the most effective ways to use nanoparticles to heat tumors and stimulate anti-tumor immunity.

According to Fiering, this approach is far from new, “The use of heat to treat cancer was first recorded by ancient Egyptians. But has reemerged with high tech modern systems as a contributor to the new paradigm of fighting cancer with the patients’ own immune system.”

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