RISK OF PANCREATIC CANCER LINKED TO VARIATION IN GENE THAT DETERMINES BLOOD TYPE

A gene variation or gene defect has been found that increases the risk of pancreatic cancer, which is one of the deadliest of all cancers. - BRH

RISK OF PANCREATIC CANCER LINKED TO VARIATION IN GENE THAT DETERMINES BLOOD TYPE
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U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Cancer Institute (NCI)
Embargoed for Release: Sunday, August 2, 2009, 1 p.m., EDT

CONTACT: NCI Office of Media Relations, 301-496-6641,

RISK OF PANCREATIC CANCER LINKED TO VARIATION IN GENE THAT DETERMINES BLOOD TYPE

Common variants of the gene that determines human blood type are associated with an increased risk of pancreatic cancer, according to a study by scientists at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues from many universities and research institutions. The study, published online Aug. 2, 2009, in Nature Genetics, is consistent with an observation first made more than 50 years ago.

In the study, the researchers discovered that genetic variation in a region of chromosome 9 that contains the gene for ABO blood type was associated with pancreatic cancer risk. Individuals with the variant that results in blood types A, B, or AB were at an increased risk of pancreatic cancer, compared to those with the variant for blood type O. This finding is consistent with previous research, some of it dating back to the 1950s and 1960s, that had shown increased risks of gastric and pancreatic cancer among individuals of the A and B blood groups (i.e., blood types A, B, and AB). The latest results provide a genetic basis for those earlier observations.

A person's blood type depends on which form or forms of the ABO gene they inherit from their parents. The protein produced by the ABO gene determines the type of carbohydrates (complex sugars) that are present on the surface of red blood cells and other cells, including cells of the pancreas. The proteins encoded by the A and B forms of the gene transfer different carbohydrates onto the cell surfaces to make A and B blood types. The O form encodes a protein that is unable to transfer carbohydrates. Studies by other researchers have shown that ABO protein encoding in pancreatic tumor cells is different than in normal pancreatic cells.

To discover genetic variations that contribute to pancreatic cancer risk, the research team conducted a genome-wide association study (GWAS). In a GWAS, researchers analyze common variants, called single-nucleotide polymorphisms (SNPs), in the genomes of people with a disease and people without the disease. Initially, the research team studied the genomes of 1,896 patients with pancreatic cancer and 1,939 control subjects to identify SNPs with a strong association with pancreatic cancer. The team then verified its findings by studying the genomes of another 2,457 people with pancreatic cancer and 2,654 people without the disease. In the end, they identified several SNPs on the long arm of chromosome 9 that were associated with pancreatic cancer risk and mapped to the ABO gene.

"Only by working across disciplines and with more than a dozen research groups were we able to make this important discovery of the potential role of the ABO gene in pancreatic cancer risk," said co-author Patricia Hartge, Sc.D., of NCI's Division of Cancer Epidemiology and Genetics (DCEG). "Although it will take much more work, this finding may lead to improved diagnostic and therapeutic interventions that are so desperately needed."


Pancreatic cancer is the fourth leading cause of cancer death in the United States. It is difficult to detect, and in many people it is not diagnosed until after the disease has spread to other parts of the body. Less than five percent of Americans with pancreatic cancer survive five years past diagnosis. Risk factors include smoking, diabetes, race, and a family history of the disease.

"Pancreatic cancer is the newest beneficiary of so-called high-throughput genotyping that, over the past two years, has yielded scores of genetic hot-spots linked to risk for cancer and other diseases," said co-author Stephen J. Chanock, M.D., chief of NCI's Laboratory of Translational Genomics in DCEG. "As more variants are discovered and follow-up studies are conducted to examine the biological effects of these variants, a better understanding will emerge of the inherited risk factors and mechanisms that lead to the development of pancreatic cancer."

The study was part of PanScan, a GWAS of pancreatic cancer conducted by the Pancreatic Cancer Cohort Consortium, composed of 14 academic centers. The investigators are conducting whole-genome scans to identify common genetic variants that may be markers of susceptibility to pancreatic cancer.

Analyses and data from PanScan will be available through NCI's caBIG (Cancer Biomedical Informatics Grid). The summary results for similar data on breast and prostate cancer are already freely available to other researchers at this Web site.

For more information on Dr. Hartge's research, please go to .

For more information on Dr. Chanock's research, please go to .

For more information about PanScan, please go to .

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit .
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REFERENCE: Amundadottir L., et al. Genome-wide association study identifies ABO Blood Group Susceptibility Variants for Pancreatic Cancer. "Nature Genetics." Online August 2, 2009.

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Keywords: National Institute of Health, United States, National Cancer Institute, Genome-wide association study, United States Department of Health and Human Services, National Cancer Program, Single-nucleotide polymorphism

GENES KEY TO STAPH DISEASE SEVERITY, DRUG RESISTANCE FOUND HITCHHIKING TOGETHER

A new study finds that resistance and virulence can travel together. - BRH

GENES KEY TO STAPH DISEASE SEVERITY, DRUG RESISTANCE FOUND HITCHHIKING TOGETHER

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Allergy and Infectious Diseases (NIAID)
For Immediate Release: Friday, July 31, 2009

CONTACT: Ken Pekoc, 301-402-1663

GENES KEY TO STAPH DISEASE SEVERITY, DRUG RESISTANCE FOUND HITCHHIKING TOGETHER

Scientists studying Staphylococcus bacteria, including methicillin-resistant S. aureus (MRSA), have discovered a potent staph toxin responsible for disease severity. They also found the gene for the toxin traveling with a genetic component of Staphylococcus that controls resistance to antibiotics. The study, now online in PLoS Pathogens, shows for the first time that genetic factors that affect Staphylococcus virulence and drug resistance can be transferred from one strain to another in one exchange event.

One of the ways Staphylococcus bacteria become drug-resistant is through horizontal gene transfer, whereby resistance genes move from one bacterium to another. Staph bacteria also can exchange virulence genes using the same mechanism, but this was previously assumed to occur separately from the transfer of antibiotic resistance.

Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health, led the study. They collaborated with researchers at the University of Tubingen in Germany and the University of Medicine and Dentistry of New Jersey.

"The discovery that bundled genes determine virulence and antimicrobial resistance suggests a new research focus for scientists trying to better prevent and treat serious staph infections," says Anthony S. Fauci, M.D., NIAID director.

The research involved more than 100 strains of S. aureus and S. epidermidis, both bacteria found on the skin of most people. In recent decades, these bacteria have become increasingly virulent, often causing severe disease that can be resistant to traditional antibiotics such as methicillin.

The studies were directed by NIAID senior investigator Michael Otto, Ph.D. In 2007, he and his colleagues found that staphylococci secrete toxins of the phenol-soluble modulin (PSM) family that are primarily responsible for attracting and killing human white blood cells called neutrophils. This process is critical for the ability of S. aureus-including community-acquired MRSA-to cause disease.

While screening S. aureus and S. epidermidis strains, Dr. Otto's group noticed that some strains produced one additional, previously unknown PSM toxin. The researchers hypothesized that the toxin was somehow connected to drug resistance. This idea surfaced because the toxin appeared in 10 percent of all MRSA strains and 68 percent of all methicillin-resistant S. epidermidis strains analyzed-whereas the researchers did not find it in strains of S. aureus or S. epidermidis that are sensitive to methicillin.

The research group confirmed its theory by identifying the specific location that encodes the toxin, which was in gene clusters that control drug resistance, known as SCCmec. The group named the new toxin PSM-mec.

"This work represents a previously unknown example of a toxin hitchhiking on staphylococcal mobile genetic elements that are primarily in charge of transferring antibiotic resistance," says Dr. Otto. He adds that the finding "should alert the research community that aggressive, drug-resistant staph can evolve more quickly than we assumed."

The research group is continuing its study of PSM-mec in S. epidermidis, where the toxin is more prevalent. Ultimately, being able to neutralize PSM-mec and other toxins that attack human defenses could lead to new treatments for S. aureus and S. epidermidis disease.

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at .

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit .

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DR. WILLIAM MATTHEW TAPPED TO LEAD NINDS OFFICE OF TRANSLATIONAL RESEARCH

This is interesting to me. I'd like to know why someone would leave the private research sector right now for an NIH job. What is the pay rate for each position? And will he really tap into patient advocacy groups? - BRH

DR. WILLIAM MATTHEW TAPPED TO LEAD NINDS OFFICE OF TRANSLATIONAL RESEARCH

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Neurological Disorders and Stroke (NINDS)
For Immediate Release: Thursday, July 30, 2009

CONTACT: Margo Warren, NINDS, 301-496-5924,

DR. WILLIAM MATTHEW TAPPED TO LEAD NINDS OFFICE OF TRANSLATIONAL RESEARCH

The National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, has named William D. Matthew, Ph.D., as director of its Office of Translational Research (OTR).

Dr. Matthew will lead the Institute's efforts to translate the results of laboratory research into treatments for neurological disorders. Dr. Matthew was formerly Vice President of R&D Partnering and Business Development at UCB, an international biopharmaceutical company based in Brussels. He holds a Ph.D. in biochemistry from the University of California, San Francisco (UCSF), and has served on the faculty of Harvard Medical School in Boston and Duke University Medical Center in Durham, N.C.

"Moving treatments for neurological disorders from the lab bench to the bedside is one of the most important missions of the NINDS and also our most formidable challenge," said Story C. Landis, Ph.D., director of NINDS. "Dr. Matthew's experience in academic research and in drug development -- and especially his ability to bridge those two worlds -- will energize and focus our translational research efforts."

An untold number of potential therapeutic drugs disappear into a critical gap between academia and industry. Academia is the main source of insights into the mechanisms of disease -- and hence insights into potential drug targets -- but few academic scientists have the means to develop a drug. Meanwhile, pharmaceutical companies have the resources to formulate a drug and test it in clinical trials, but they cannot invest in a drug without some sign of market value.

The NINDS OTR aims to close this gap and accelerate drug development for neurological disorders. The OTR replaces the NINDS Office of Technology Development, and will build on NINDS' existing programs in translational neuroscience research. Dr. Matthew was selected to lead the OTR because his career ranges from academic neuroscience research to all stages of the drug development process.

At the beginning of his career, Dr. Matthew helped pioneer the use of antibodies as tools for neuroscience research and as therapies for neurological disease. (Antibodies are a part of the body's immune defenses, and work by attaching to foreign cells and marking them for destruction.) As a doctoral student at UCSF, Dr. Matthew developed antibodies that could be used to isolate and characterize proteins inside nerve cells. In the early 1980s, as a professor at Harvard Medical School, he was among the first to develop antibodies that modulate the function of proteins critical for neural activity. Antibodies of this kind are now used to treat multiple sclerosis and are under investigation in patients with Alzheimer's disease.

In 1990, Dr. Matthew moved to Duke University Medical Center to help establish the Neurobiology Department, and in 1998, he became scientific director of The George and Jean Brumley Neonatal-Perinatal Research Institute within Duke's Department of Pediatrics. The Institute's primary mission is to "explore the basis for birth defects and neonatal injury of the brain and lungs and translate the findings into clinical practice."

In 2001, Dr. Matthew was recruited to Schwarz Pharma, a mid-sized German-based drug company. Dr. Matthew was integral to building Schwarz Biosciences, a new research and development division, which involved establishing the company's first research labs, as well as partnering with academic labs and with other pharmaceutical companies. Schwarz Pharma grew substantially over the next six years, and was acquired by UCB in 2007. During his tenure there, Schwarz Pharma developed three new drug products for the U.S. and European markets:

-- Neupro (rotigotine) - a skin patch for stable, continuous relief from the symptoms of Parkinson's disease.
-- Vimpat (lacosamide) - a drug for treatment-resistant epilepsy.
-- Toviaz (fesoterodine) - a drug for symptomatic relief from overactive bladder.

As director of NINDS OTR, Dr. Matthew will oversee several NINDS initiatives that support translational research. He also will play a key role in NIH-wide translational research initiatives. These include the NINDS Cooperative Program in Translational Research which funds the preclinical optimization and testing of lead compounds into new drugs, and the NINDS Anticonvulsant Screening Program which has played a pivotal role in the discovery and development of drugs for epilepsy, including Vimpat.

Dr. Matthew is looking forward to bringing his diverse experiences to NINDS. "In the time since I began my career, neuroscientists have gained key insights into many neurological disorders, and created many opportunities for new treatments. My goal is to tap into the unique strengths of researchers, physicians, patient advocacy groups, and industry and government leaders so that we can turn those opportunities into realities," he said.

The NINDS is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease - a burden borne by every age group, by every segment of society, by people all over the world. For more information about the NINDS Office of Translational Research, visit .

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit .

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SUN EXPOSURE MAY TRIGGER CERTAIN AUTOIMMUNE DISEASES IN WOMEN

More bad news for women. The sun may trigger autoimmune disease.

SUN EXPOSURE MAY TRIGGER CERTAIN AUTOIMMUNE DISEASES IN WOMEN

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Environmental Health Sciences (NIEHS)
For Immediate Release: Thursday, July 30, 2009

CONTACT: Robin Mackar, 919-541-0073,

SUN EXPOSURE MAY TRIGGER CERTAIN AUTOIMMUNE DISEASES IN WOMEN

Ultraviolet (UV) radiation from sunlight may be associated with the development of certain autoimmune diseases, particularly in women, according to a study by researchers at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.

"This study found that women who lived in areas with higher levels of UV exposure when they developed an autoimmune muscle disease called myositis were more likely to develop the form known as dermatomyositis, which weakens the muscles and causes distinctive rashes, instead of the form called polymyositis that does not have a rash," said Frederick W. Miller, M.D., Ph.D., chief of the Environmental Autoimmunity Group, Program of Clinical Research, at NIEHS. "Although we have not shown a direct cause and effect link between UV exposure and this particular autoimmune disease, this study confirms the association between UV levels and the frequency of dermatomyositis that we found in a previous investigation," said Miller.

The study, published in the August issue of Arthritis & Rheumatism, is also the first to evaluate and find a possible UV radiation association in autoimmune diseases in women.

According to Miller, women are more likely than men to develop many autoimmune diseases, but the reasons for this have not been clear. "We only found the association between UV exposure and dermatomyositis in women and not in men, and it could be that inherent differences in how women and men respond to UV radiation may play a role in the development of certain autoimmune diseases," said Dr. Miller. Miller also noted that other researchers have shown that female mice develop more skin inflammation after UV light exposure compared to male mice and these effects may be related to the new findings in dermatomyositis.

The study was designed to determine if there was a relationship between the level of UV exposure at the onset of the disease and the type of myositis and autoantibodies that people developed. Dermatomyositis and polymyositis are the two major forms of myositis and both are considered autoimmune diseases, in which the body's immune system attacks muscle or skin and sometimes other tissues. Dermatomyositis is typically accompanied by a distinctive reddish-purple rash on the upper eyelids or over the knuckles and is often made worse with sun exposure.

To conduct the study, the NIEHS researchers collaborated with myositis centers across the country that had seen 380 patients who had been diagnosed with dermatomyositis or polymyositis and determined their autoantibodies. "Patients with autoimmune diseases make a variety of autoantibodies that are unique to different conditions. One autoantibody specifically associated with dermatomyositis is called the anti-Mi-2 autoantibody and we know from our previous research that UV radiation increases levels of the Mi-2 protein that this autoantibody binds to," said Miller.

In addition to finding an association between the level of UV radiation and the proportion of women who developed dermatomyositis compared to polymyositis, the researchers found an association between UV levels and the proportion of women with the anti-Mi-2 autoantibody. "More research is clearly needed to understand the potential links between UV radiation and the development of autoimmune diseases and autoantibodies in women," said Miller.

"While the causes of autoimmune diseases are not known, we suspect from emerging research that they develop after one or more environmental exposures in genetically susceptible people," said NIEHS Director Linda Birnbaum, Ph.D. "This study adds UV radiation to the growing list of environmental exposures possibly important in the development of autoimmune diseases."

The NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit our Web site at .

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit .
--------------------------
REFERENCE: Love LA, Weinberg CR, McConnaughey DR, Oddis CV, Medsger TA, Reveille JD, Arnett FC, Targoff IN, Miller FW. "Ultraviolet Radiation Intensity Predicts the Relative Distribution of Dermatomyositis and Anti-Mi-2 Autoantibodies in Women." Arthritis & Rheumatism. August, 2009.

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SUN EXPOSURE MAY TRIGGER CERTAIN AUTOIMMUNE DISEASES IN WOMEN

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Environmental Health Sciences (NIEHS)
For Immediate Release: Thursday, July 30, 2009

CONTACT: Robin Mackar, 919-541-0073,

SUN EXPOSURE MAY TRIGGER CERTAIN AUTOIMMUNE DISEASES IN WOMEN

Ultraviolet (UV) radiation from sunlight may be associated with the development of certain autoimmune diseases, particularly in women, according to a study by researchers at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.

"This study found that women who lived in areas with higher levels of UV exposure when they developed an autoimmune muscle disease called myositis were more likely to develop the form known as dermatomyositis, which weakens the muscles and causes distinctive rashes, instead of the form called polymyositis that does not have a rash," said Frederick W. Miller, M.D., Ph.D., chief of the Environmental Autoimmunity Group, Program of Clinical Research, at NIEHS. "Although we have not shown a direct cause and effect link between UV exposure and this particular autoimmune disease, this study confirms the association between UV levels and the frequency of dermatomyositis that we found in a previous investigation," said Miller.

The study, published in the August issue of Arthritis & Rheumatism, is also the first to evaluate and find a possible UV radiation association in autoimmune diseases in women.

According to Miller, women are more likely than men to develop many autoimmune diseases, but the reasons for this have not been clear. "We only found the association between UV exposure and dermatomyositis in women and not in men, and it could be that inherent differences in how women and men respond to UV radiation may play a role in the development of certain autoimmune diseases," said Dr. Miller. Miller also noted that other researchers have shown that female mice develop more skin inflammation after UV light exposure compared to male mice and these effects may be related to the new findings in dermatomyositis.

The study was designed to determine if there was a relationship between the level of UV exposure at the onset of the disease and the type of myositis and autoantibodies that people developed. Dermatomyositis and polymyositis are the two major forms of myositis and both are considered autoimmune diseases, in which the body's immune system attacks muscle or skin and sometimes other tissues. Dermatomyositis is typically accompanied by a distinctive reddish-purple rash on the upper eyelids or over the knuckles and is often made worse with sun exposure.

To conduct the study, the NIEHS researchers collaborated with myositis centers across the country that had seen 380 patients who had been diagnosed with dermatomyositis or polymyositis and determined their autoantibodies. "Patients with autoimmune diseases make a variety of autoantibodies that are unique to different conditions. One autoantibody specifically associated with dermatomyositis is called the anti-Mi-2 autoantibody and we know from our previous research that UV radiation increases levels of the Mi-2 protein that this autoantibody binds to," said Miller.

In addition to finding an association between the level of UV radiation and the proportion of women who developed dermatomyositis compared to polymyositis, the researchers found an association between UV levels and the proportion of women with the anti-Mi-2 autoantibody. "More research is clearly needed to understand the potential links between UV radiation and the development of autoimmune diseases and autoantibodies in women," said Miller.

"While the causes of autoimmune diseases are not known, we suspect from emerging research that they develop after one or more environmental exposures in genetically susceptible people," said NIEHS Director Linda Birnbaum, Ph.D. "This study adds UV radiation to the growing list of environmental exposures possibly important in the development of autoimmune diseases."

The NIEHS supports research to understand the effects of the environment on human health and is part of NIH. For more information on environmental health topics, visit our Web site at .

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit .
--------------------------
REFERENCE: Love LA, Weinberg CR, McConnaughey DR, Oddis CV, Medsger TA, Reveille JD, Arnett FC, Targoff IN, Miller FW. "Ultraviolet Radiation Intensity Predicts the Relative Distribution of Dermatomyositis and Anti-Mi-2 Autoantibodies in Women." Arthritis & Rheumatism. August, 2009.

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This NIH News Release is available online at:
.

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