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Biomarker Roundup No. 4

December 9, 2014

Lung Cancer

Genetic variants may predict suitability of alcoholism drug for patients
A team of scientists led by the Mayo Clinic discovered that variants of the gene GRIN2B may correspond to how well individuals respond to the medication acamprosate, which is prescribed to treat people who are recovering from alcohol addiction. The study is published in the journal Translational Psychiatry.

This conclusion is based on a study of individuals who received an acamprosate prescription as part of a community-based alcoholism treatment program. Genetic analyses of patient samples indicated that certain variants of the rs2058878 polymorphism in the GRIN2B gene were associated with a longer period of sobriety during treatment. These findings were replicated in another group of patients in Germany.

“This association finding is a first step towards development of a pharmacogenetic test allowing physicians to choose appropriate treatment for specific subgroups of alcohol-dependent patients,” lead study author Victor Karpyak, M.D., Ph.D., Mayo Clinic psychiatrist, said in a statement. He added that these results may lead to more individualized approaches to alcoholism treatment, which will potentially save time spent on a trial-and-error approach to patients’ recovery.

Further studies are needed to determine the implications of this discovery.

Asthma-induced inflammation may be genotoxic beyond the lungs
Although asthma is considered a chronic illness of the respiratory system, the inflammation that characterizes the disease may have more repercussions than previously thought. Specifically, a research team from UCLA observed that inflammatory cytokines corresponding to asthma drove chain reactions that can lead to DNA damage in cells and organs outside the lungs, as published in the journal Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis.

With the help of rodent models of human asthma, the study authors observed that interleukin 13, a cytokine that is associated with cancer, raised the levels of reactive oxygen species in peripheral blood. This oxidative stress led to DNA damage, single- and double-strand DNA breaks, the formation of micronuclei and protein damage – all of which destabilize the chromosomes.

“Asthma is a very widespread disease, and we show for the first time an association between asthma and genotoxicity in peripheral blood,” senior author Robert Schiestl said in a statement. “This is important because it shows a whole-body effect from asthma, not just damage in the lungs.”

The next step in this research is to determine whether the administration of certain chemical compounds will repair this DNA damage.

Lung cancer patients exhibit different metabolite profiles
Any stakeholders in cancer treatment understand that early detection is key to recovery. To that end, one team of researchers from the Cleveland Clinic asserted that individuals who have non-small cell lung cancer tend to produce different metabolites compared to people who are at risk for the disease but do not have it. These results were published in the journal CHEST and presented at CHEST 2014, the annual meeting of the American College of Chest Physicians.

To find out more about the metabolites produced by lung cancer patients, the study authors conducted an experiment that included 284 subjects who were diagnosed with adenocarcinoma or squamous lung cancer. Forty-four percent, 17 percent and 39 percent of these research participants were at stages I, II, or III, respectively. Additionally, the experiment included 194 other people who were not sick and were matched to the cancer patients according to age, gender, smoking history, and other factors.

Blood serum analyses of 534 metabolites revealed that cancer patients produced 149 metabolites in greater quantities than what was observed in cancer-free subjects.

“Our study results showed that patients with lung cancer have altered metabolic processes,” researcher Peter Mazzone, M.D., F.C.C.P., said in a statement. “This information could lead to the development of a diagnostic biomarker for early detection of lung cancer.”

Intestinal microbes may act as biomarker for immune disorder
A growing number of research studies are exploring the link between the populations of microbes living within individuals’ intestinal systems and their health. For example, one team of scientists from Virginia Polytechnic Institute and State University discovered that the overpopulation of one specific microbial species may be indicative of severe combined immunodeficiency, as published in The ISME Journal.

This conclusion is based on laboratory analyses of mice that were either healthy or had weak immune systems. In the latter population, the level of Akkermansia muciniphila microbes in the gut was far greater than in the healthy mice. However, after a bone marrow transplant, levels of this microbial species went back to normal.

“This is also a human intestinal microbe,” study co-author Husen Zhang said in a statement. “Although it is rather newly discovered, it has been there for a long time. Previous reports found that the microbe increases with antibiotic use, indicating that it might thrive when other gut microbes don’t survive a round of antibiotics.”

In the future, SCID or similar immune deficiencies may be diagnosed in human infants by analyzing the microbes found in their feces.