CARBOHYDRATE DIGESTION AND OBESITY STRONGLY LINKED

New research indicates that obesity in the general population may be genetically linked to how our bodies digest carbohydrates. The study investigated the relationship between body weight and a gene called AMY1, which is responsible for an enzyme present in our saliva known as salivary amylase. This enzyme is the first to be encountered by food when it enters the mouth, and it begins the process of starch digestion that then continues in the gut.

People usually have two copies of each gene, but in some regions of our DNA there can be variability in the number of copies a person carries, which is known as copy number variation. The number of copies of AMY1 can be highly variable between people, and it is believed that higher numbers of copies of the salivary amylase gene have evolved in response to a shift towards diets containing more starch since prehistoric times.

Researchers from Imperial College London, in collaboration with other international institutions, looked at the number of copies of the gene AMY1 present in the DNA of thousands of people from the UK, France, Sweden and Singapore. They found that people who carried a low number of copies of the salivary amylase gene were at greater risk of obesity.

The chance of being obese for people with less than four copies of the AMY1 gene was approximately eight times higher than in those with more than nine copies of this gene. The researchers estimated that with every additional copy of the salivary amylase gene there was approximately a 20 per cent decrease in the odds of becoming obese.

Professor Philippe Froguel, Chair in Genomic Medicine in the School of Public Health at Imperial College London, and one of the lead authors on the study, said: "I think this is an important discovery because it suggests that how we digest starch and how the end products from the digestion of complex carbohydrates behave in the gut could be important factors in the risk of obesity. Future research is needed to understand whether or not altering the digestion of starchy food might improve someone's ability to lose weight, or prevent a person from becoming obese. We are also interested in whether there is a link between this genetic variation and people's risk of other metabolic disorders such as diabetes, as people with a low number of copies of the salivary amylase gene may also be glucose intolerant."

Previous studies have found rare genetic variations causing extreme forms of obesity, but because they occur in only a small number of people, they explained very little of the differences in body weight we see in the population. On the other hand, research on more common genetic variations that increase risk of obesity in the general population have so far generally found only a modest effect on obesity risk. This study is novel in that it identifies a genetic variation that is both common and has a relatively large effect on the risk of obesity in the general population. The number of copies of the salivary amylase gene is highly variable between people, and so, given this finding, can potentially have a large impact on our individual risk of obesity.

The first step of the study involved the analysis of genetic data from a Swedish family sample of 481 participants, recruited on the basis of sibling-pairs where one was obese and the other non-obese. The researchers used these data to short-list genes whose copy number differences influence body mass index (BMI), and identified the gene coding for the enzyme salivary amylase (AMY1) as the one with the greatest influence on body weight in their analysis. They then investigated the relationship between the number of times the AMY1 gene was repeated on chromosome 1 in each individual and their risk of obesity, by studying approximately 5,000 subjects from France and the UK.

Story Source:

The above story is based on materials provided by Imperial College London. Note: Materials may be edited for content and length.

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Journal Reference:

1. M. Falchi et al. Low copy number of the salivary amylase gene predisposes to obesity. Nature Genetics, 2014 DOI: 10.1038/ng.2939

Sugar: time bomb....

New sugar limits: 26 'mini health time bombs' http://www.telegraph.co.uk/health/healthnews/10680467/New-sugar-limits-26-mini-health-time-bombs.html

Project Work in Medical Biochemistry and Microbiology 2013/2014 - Uppsala University, Sweden

Project Work in Medical Biochemistry and Microbiology 2013/2014 - Uppsala University, Sweden

Early tumor response from stereotactic radiosurgery predicts outcome

The response of a patient with metastatic brain tumors to treatment with stereotactic radiosurgery in the first six-to-twelve weeks can indicate whether follow-up treatments and monitoring are necessary, according to research conducted at the University of North Carolina School of Medicine.

          The study of 52 patients with metastatic brain legions, found that the tumors whose sizes decreased significantly after treatment with stereotactic radiosurgery (SRS) did not resume growth or require additional treatment. The research, conducted by a team led by Matthew G. Ewend, MD, chair of the UNC Department of Neurosurgery and member of the UNC Lineberger Comprehensive Cancer Center, could reduce the need to continually monitor patients who respond well to SRS.

 The volume of the tumors over time was measured to see the outcome, based on what happened in the beginning, what would happen long term.It was that tumors that did not shrink in the beginning were more likely later to be correlated to a patient having a neurological problem or needing steroids. If they did shrink, they were more likely to stay under control long term."

The advent of SRS systems allows physicians to target tumors with precise, high-dose beams of radiation. While the technique is in widespread use, current practice requires repeated check-ups to determine its effectiveness. The results of this study indicate that this monitoring may only be necessary for patients who do not respond favorably within the first six to twelve weeks after SRS treatment.

 few MRIs  scans are necessary afterwards for a good response.

Between 20 and 40 percent of adults with cancer develop brain tumors, which metastasize from cancers elsewhere in the body. The number of brain tumors treated by physicians has increased, as better treatments for the cancers that spawn them increase patient survival. Because of the systemic nature of these cancers, the survival implications of positive early response depend largely on how patients respond to therapy for their initial cancer.

"This is not in a vacuum. Even if you control the brain disease, they can still die of their other disease. With better control of the brain disease, the patients have a better chance of living longer, but it will take both improvements in systemic therapy and brain therapy," said Dr. Ewend.

The UNC study included patients with lung, breast, melanoma and renal cell cancers. It builds on prior research that indicated a similar response in patients with clear cell renal cancer. Dr. Ewend said that future research will need to increase the number of patients to reinforce the results and determine what factors influence positive early response. One possibility for future research is to determine the genetic factors behind tumor response, which will allow researchers to develop a genetic test to help predict a patient's outcome.

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Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.

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Journal Reference: Suzanne R. Sharpton, Eric K. Oermann, Dominic T. Moore, Eric Schreiber, Riane Hoffman, David E. Morris, Matthew G. Ewend. The Volumetric Response of Brain Metastases After Stereotactic Radiosurgery and Its Post-treatment Implications. Neurosurgery, 2014; 74 (1): 9 DOI: 10.1227/NEU.0000000000000190

DIFFERENT CANCER SAME MUTATION

 

An astounding variety of genetic abnormalities can cause healthy cells to turn cancerous. Few of these are shared among cancers of the same tissue, and fewer still are shared among cancers of different tissues. Nevertheless, scientists searching for such common genetic needles in an array of cancer.

“For the first time we have been able to analyze, across the board, large numbers of tumor samples . . . and also systematically look across different tumor types,” said Chris Sander, chair of the computational biology program at the Memorial Sloan-Kettering Cancer Center in New York, and senior author on one of the new papers. The main aim was to learn about principles of cancer biology that might not have been obvious from previous studies examining one tumor type in isolation.

“TCGA is all about analyzing each tumor type separately,” said Josh Stuart, a professor of biomolecular engineering at the University of California, Santa Cruz, who was not involved in either study. ON every time a new experiment is carried out in cancer, we always wanted to compare it to the previous one and it has been analyzed that there is some kind of  similarities.

One benefit of looking at cancer samples from all tissue types is that the pool of data becomes larger, offering more statistical power. .

A scientist team examined DNA copy number alterations—common features in cancer—at roughly 1.5 million loci across the genome. They found approximately 200,000 copy number alterations in total, which worked out to about 39 alterations per cancer sample.

To determine which of these alterations might be causing cancer, the researchers looked for only those that recurred across various cancer types. By doing so, they whittled down the 200,000 or so loci to just 140. Only 35 of these loci contained known oncogenes or tumor suppressor genes, meaning the remaining 105 contained new cancer-causing candidates to investigate.

Another scientist  team—which studied gene mutations and DNA methylation changes in addition to copy number alterations—similarly whittled down many thousands of such genetic aberrations to just 479 that were recurrent across multiple cancer types.

The team then asked which of these 479 genetic events occurred in each cancer sample, paving the way for new categories of cancer based on the particular constellations of aberrations they possessed. Interestingly, the team found that cancers with abundant single gene mutations tended not to have many copy number alterations and vice versa.

The two team  come to in conclusion is that they have a spectrum of tumors that are driven by copy number abnormalities  and then another set of tumors that are driven primarily by a series of mutational events. The two papers provided a very cogent argument that these are two of the major driving events.

Beyond learning more about the mechanisms behind the disease’s origins, such cancer studies might lead to a new kind of clinical trial. Sander described such studies as basket or matrix trials, in which patients with different tumor types—for example, breast, ovarian, or colorectal—but similar constellations of genetic alterations, would be treated with the same drug or drugs.

 It’s possible that the same mutation in different cancer types could indicate different responses to drugs.

REFERNCE-

G. Ciriello et al., “Emerging landscape of oncogenic signatures across human cancers,” Nature Genetics, doi:10.1038/ng.2762, 2013.

T. I. Zack et al., “Pan-cancer patterns of somatic copy number alteration,” Nature Genetics,doi:10.1038/ng.2760, 2013.