NIH STUDY REVEALS NEW GENETIC CULPRIT IN DEADLY SKIN CANCER

New information may lead to a new treatment for deadly melanoma. This is why genetic testing is so important. - BRH

NIH STUDY REVEALS NEW GENETIC CULPRIT IN DEADLY SKIN CANCER
Sequencing Work Points to New Target for Melanoma Treatment

Drawing on the power of DNA sequencing, National Institutes of Health researchers have identified a new group of genetic mutations involved in the deadliest form of skin cancer, melanoma. This discovery is particularly encouraging because some of the mutations, which were found in nearly one-fifth of melanoma cases, reside in a gene already targeted by a drug approved for certain types of breast cancer.

In the United States and many other nations, melanoma is becoming increasingly more common. A major cause of melanoma is thought to be sun exposure; the ultraviolet radiation in sunlight can damage DNA and lead to cancer-causing genetic changes within skin cells.

In work published in the September issue of Nature Genetics, a team led by Yardena Samuels, Ph.D., of the National Human Genome Research Institute (NHGRI) sequenced the protein tyrosine kinase (PTK) gene family in tumor and blood samples from people with metastatic melanoma. The samples were collected by the study's coauthor Steven Rosenberg, M.D., Ph.D., a leading expert on melanoma and chief of surgery at the National Cancer Institute (NCI).

The PTK family includes many genes that, when mutated, promote various types of cancer. However, relatively little had been known about roles played by PTK genes in human melanoma. The NIH study was among the first to use large-scale DNA sequencing to systematically analyze all 86 members of the PTK gene family in melanoma samples.

The team's initial survey, which involved samples from 29 melanoma patients, identified mutations in functionally important regions of 19 PTK genes, only three of which had been previously implicated in melanoma. The researchers then conducted more detailed analyses of those 19 genes in samples from a total of 79 melanoma patients.

One of the newly implicated genes stood out from the rest. Researchers detected mutations in the ERBB4 gene (also known as HER4) in 19 percent of patients' tumors, making it by far the most frequently mutated PTK gene in melanoma. In addition, researchers found that many ERBB4 mutations were located in functionally important areas similar to those seen in other PTK oncogenes involved in lung cancer, brain cancer and gastric cancer.

Next, the researchers moved on to laboratory studies of melanoma cells with ERBB4 mutations. They found that these melanoma cells were dependent on the presence of mutant ERBB4 for their growth. What's more, the melanoma cells grew much more slowly when they were exposed to a chemotherapeutic drug known to inhibit ERBB4. The drug, called lapatinib (Tykerb), was approved by the Food and Drug Administration in 2007 for combination use in breast cancer patients already taking the drug capecitabine (Xeloda).

Encouraged by their study results, the researchers are planning a clinical trial using lapatinib in patients with metastatic melanoma harboring ERBB4 mutations. The clinical trial will be conducted under the direction of Dr. Rosenberg at the NIH Clinical Center. "This collaborative study represents an ideal example of how sophisticated genetic analyses can be translated to the benefit of cancer patients," said Dr. Rosenberg.

"We have found what appears to be an Achilles' heel of a sizable share of melanomas," said Dr. Samuels, who is an investigator in the Cancer Genetics Branch of the NHGRI's Division of Intramural Research. "Though additional work is needed to gain a more complete understanding of these genetic mutations and their roles in cancer biology, our findings open the door to pursuing specific therapies that may prove useful for the treatment of melanoma with ERBB4 mutations."

In addition to ERBB4, the researchers identified two additional PTK genes, FLT1 and PTK2B, with a relatively high rate of mutations in melanoma. Each of these genes was mutated in about 10 percent of the tumor samples studied.

NHGRI Scientific Director Eric D. Green, M.D., Ph.D., pointed out how such research is helping to lay the groundwork for the era of personalized medicine. "We envision a day when each cancer patient will have therapies tailored to the specific genetic profile of his or her tumor. Ultimately, this should lead to more effective and less toxic approaches to cancer care," said Dr. Green, who directs the NIH Intramural Sequencing Center, which generated the DNA sequence data for the melanoma study.

In addition to NIH scientists, the team included a researcher from the Johns Hopkins Kimmel Cancer Center in Baltimore.

In May 2009, Dr. Samuel's group reported in Nature Genetics another large-scale DNA sequencing study of a different group of genes involved in melanoma, the matrix metalloproteinase (MMP) gene family. This earlier study found that one gene, MMP-8, thought to spur cancerous growth actually served to inhibit it. Those findings are now helping to shape melanoma treatment strategies aimed at MMP genes.

For high resolution micrographs of metastatic melanoma, go to and .

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).



NHGRI is one of the 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information about NHGRI can be found at its Web site, .

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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The NIH has a New Director

The NIH has sworn in a new director. Francis S. Collins, MD, PhD. He was a leader of the Human Genome Project. - BRH

FRANCIS S. COLLINS, M.D., PH.D., SWORN IN AS NIH DIRECTOR
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For Immediate Release: Monday, August 17, 2009

CONTACT: NIH Office of Communications, 301-496-5787,

FRANCIS S. COLLINS, M.D., PH.D., SWORN IN AS NIH DIRECTOR

Francis S. Collins, M.D., Ph.D., today became the 16th director of the National Institutes of Health. He was nominated to lead the NIH, the nation's premiere biomedical research agency, by President Barack Obama on July 8, and was unanimously confirmed by the U.S. Senate on August 7.

In his July 8 nomination announcement, President Obama stated: "The National Institutes of Health stands as a model when it comes to science and research. My administration is committed to promoting scientific integrity and pioneering scientific research and I am confident that Dr. Francis Collins will lead the NIH to achieve these goals. Dr. Collins is one of the top scientists in the world, and his groundbreaking work has changed the very ways we consider our health and examine disease."

"As a scientist, physician, and passionate visionary, Dr. Collins will further NIH's ultimate mission to improve human health," said U.S. Health and Human Services Secretary Kathleen Sebelius. "He is an ideal choice to lead the NIH and I look forward to working closely with him."

"I am truly honored and humbled to take the helm today of the world's leading organization supporting biomedical research," Dr. Collins said. "The scientific opportunities in both the basic and clinical realms are unprecedented, and the talent and dedication of the grantees and the staff guarantee that this will be a truly exciting era."

Dr. Collins, 59, a physician-geneticist noted for his landmark discoveries of disease genes and his leadership of the Human Genome Project, served as director of NIH's National Human Genome Research Institute (NHGRI) from 1993-2008. Under his direction, the Human Genome Project consistently met projected milestones ahead of schedule and under budget. This remarkable international project culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book.

In addition to his achievements as the NHGRI director, Dr. Collins' own research laboratory discovered a number of important genes, including those responsible for cystic fibrosis, neurofibromatosis, Huntington's disease, a familial endocrine cancer syndrome, and most recently, genes for type 2 diabetes and the gene that causes Hutchinson-Gilford progeria syndrome. Dr. Collins has a longstanding interest in the interface between science and faith, and has written about this in The Language of God: A Scientist Presents Evidence for Belief (Free Press, 2006), which spent many weeks on The New York Times bestseller list. He is the author of a new book on personalized medicine, The Language of Life: DNA and the Revolution in Personalized Medicine (HarperCollins, to be published in early 2010).

Dr. Collins received a B.S. in chemistry from the University of Virginia, a Ph.D. in physical chemistry from Yale University, and an M.D. with honors from the University of North Carolina at Chapel Hill. Prior to coming to the NIH in 1993, he spent nine years on the faculty of the University of Michigan, where he was a Howard Hughes Medical Institute investigator. He is an elected member of the Institute of Medicine and the National Academy of Sciences. Dr. Collins was awarded the Presidential Medal of Freedom in November 2007.

Raynard S. Kington, M.D., Ph.D., who has served as acting NIH director since mid-October, will return to his role as NIH principal deputy director.

NIH has more than 19,000 employees and a fiscal year 2009 budget of $30.6 billion. It supports more than 325,000 research personnel at more than 3,100 institutions throughout the U.S., and around the world.

More information about Dr. Collins is available at , and a high-resolution photo is available for download 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 .

NEW DIAGNOSTIC IMAGING DEVICES AT THE NIH CLINICAL CENTER TO AUTOMATICALLY RECORD RADIATION EXPOSURE

It's about time we started keeping track of radiation exposure. I have seen the system fail to total up radiation exposures too many times and am fearful that there are going to be long term consequences for many people. Patients need total radiation exposure from X-rays, CT Scans, and dental X-rays tallied up each year. - BRH

NEW DIAGNOSTIC IMAGING DEVICES AT THE NIH CLINICAL CENTER TO AUTOMATICALLY RECORD RADIATION EXPOSURE

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
NIH Clinical Center (CC)
For Immediate Release: Monday, August 17, 2009

CONTACT: Bill Schmalfeldt, 301-496-2563,

NEW DIAGNOSTIC IMAGING DEVICES AT THE NIH CLINICAL CENTER TO AUTOMATICALLY RECORD RADIATION EXPOSURE

Radiology and Imaging Sciences at the National Institutes of Health Clinical Center has taken a significant step to further safeguard clinical research patients at the NIH Clinical Center who are exposed to radiation during certain imaging tests. Computed tomography (CT) and positron emission tomography (PET)/CT equipment purchased by the Clinical Center will now be required to routinely record radiation dose exposure in a patient's hospital-based electronic medical record.

"When a hospital or clinic patient receives a medication or a treatment, it is routinely recorded in the patient's medical record," said John I. Gallin, M.D., director of the Clinical Center, NIH's clinical research hospital in Bethesda, Md. "The Clinical Center's approach is an important first step in making it possible to more easily document and track information about a patient's exposure to radiation."

Today, electronic radiology information systems in hospitals generally do not collect or report radiation exposures. "CT and PET/ CT scanners do not currently forward data on radiation dose to our radiology information systems," said Dr. David A. Bluemke, M.D., Ph.D. Bluemke is director of Radiology and Imaging Sciences at the Clinical Center.

The risk of exposure to low doses of medical radiation from diagnostic medical-imaging tests isn't known, but very high radiation doses have the potential to cause cancer. The ability to keep track of an individual's exposure to radiation through routine imaging tests is needed so that researchers can begin to determine if these exposures pose a health risk.

"The National Council on Radiation Protection and Measurements reported recently that Americans received seven times more radiation exposure from medical tests in 2006 than was the case in the 1980s," said Ronald Neumann, M.D., chief of nuclear medicine and deputy associate director for imaging sciences at the Clinical Center. "CT and cardiac nuclear medicine studies accounted for much of this increased medical radiation exposure."

Ultimately, radiation dosage could become a standard element of a universal electronic medical record used to assess radiation risk from life-long medical testing, the Clinical Center radiologists said. "Recording radiation dose is technically possible and an ethical imperative," Neumann said.

"The NIH Clinical Center also will require that newly purchased equipment allows patients to record their radiation dose exposure in their own personal health record," Bluemke added. Online resources to help individuals organize their health information as a personal medical record are becoming more prevalent. Currently, patients can easily receive their diagnostic imaging studies records on CD-ROM, Bluemke said. The NIH Clinical Center's imaging program will work with vendors who supply Clinical Center imaging equipment to develop software tools to extract the examination type, date, and radiation dose exposure from the CD-ROM, for uploading to a personal health record. As both the American College of Radiology and the Radiological Society of North America have recommended, patients should keep a record of their X-ray history.

About 25,000 CT and 1,250 PET/CT scans are performed at the Clinical Center each year as part of NIH research protocols. The clinical research hospital currently houses five CT scanners, and two PET/CT scanners.

The NIH Clinical Center (CC) is the clinical research hospital for the National Institutes of Health. Through clinical research, physician-investigators translate laboratory discoveries into better treatments, therapies and interventions to improve the nation's health. For more information, 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 .

Hereditary Spastic Paraplegias

A new study proposes a mechanism for the hereditary spastic paraplegias. The study suggests that a gene is defective and a substance called atlastin is defective in sufferers. Without these things a protein cannot be produced that supports the endoplasmic reticulum. - BRH

FROM NERVE ROOTS TO PLANT ROOTS - RESEARCHERS ARE GAINING UNEXPECTED INSIGHTS INTO HEREDITARY SPASTIC PARAPLEGIA

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH NIH News
National Institute of Neurological Disorders and Stroke (NINDS)
Embargoed for Release: Thursday, August 6, 2009, Noon, EDT

CONTACT: Daniel Stimson, NINDS, 301-496-5751

FROM NERVE ROOTS TO PLANT ROOTS - RESEARCHERS ARE GAINING UNEXPECTED INSIGHTS INTO HEREDITARY SPASTIC PARAPLEGIA

Sprouting. Branching. Pruning. Neuroscientists have borrowed heavily from botanists to describe the way that neurons grow, but analogies between the growth of neurons and plants may be more than superficial. A new study from the National Institutes of Health and Harvard Medical School suggests that neurons and plant root cells may grow using a similar mechanism.

The research also sheds light on the hereditary spastic paraplegias (HSP), a group of inherited neurological disorders in which some of the longest neurons in the body fail to grow and function properly. The genes behind HSP and their roles inside neurons are poorly understood. However, the study suggests that several forms of HSP share an underlying defect with each other - and with abnormal root hair development in a plant widely used for agricultural research.

The strange implication is that the plant, Arabidopsis thaliana (mouse-ear cress), could prove useful for further research on HSP.

"This study provides us with valuable new insights that will stimulate research toward therapies for hereditary spastic paraplegias," says Craig Blackstone, M.D., Ph.D., an investigator at NIH's National Institute of Neurological Disorders and Stroke (NINDS) and an HSP expert. Dr. Blackstone performed the study in collaboration with William Prinz, Ph.D., an investigator at the NIH's National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Tom Rapoport, Ph.D., a Howard Hughes Medical Institute investigator and a professor of cell biology at Harvard Medical School.

HSP primarily affects corticospinal neurons, which extend projections called axons from the brain's cerebral cortex to the spinal cord. The longest corticospinal axons extend nearly all the way down the spinal cord - a distance up to about three feet - in order to control movement in the legs. In HSP, these long axons develop abnormally or they degenerate later in life, causing muscle stiffness and weakness in the legs. HSP exists in many forms in different families, and more than 40 genes have been implicated in the disease.

In the new study, published in Cell, the researchers propose that defects in the shaping of a subcellular structure known as the endoplasmic reticulum (ER) are a common cause of HSP. The ER - named for its reticulated (or net-like) shape - is a cellular factory, where molecules such as proteins and lipids that are vital to cell growth are made and packaged for shipping to various cellular destinations. The researchers theorize that in several forms of HSP, the ER loses its complex shape and is unable to support the growth or maintenance of long corticospinal axons.

Several years ago, other researchers showed that similar ER defects in Arabidopsis impair the growth of the plant's root hairs. These are wispy, microscopic projections that grow from the plant's individual root cells.

The new study focuses on a gene called atlastin. This gene is defective in about 10 percent of HSP cases, and in previous research, Dr. Blackstone's group showed that it has a role in axon growth. The new study reveals that the atlastin protein is necessary for maintaining the shape of the ER in mammalian cells, and that an analogous protein called Sey1p performs the same function in baker's yeast.

The researchers demonstrate that ER shaping defects have general relevance for HSP, by showing a connection between atlastin and a group of proteins known as the DP1 family. Years ago, Drs. Prinz and Rapoport reported that a yeast analog of DP1 regulates the shape of the ER in yeast. Meanwhile, others researchers had independently reported that mutations in REEP1, a member of the DP1 family, cause 3 percent to 8 percent of HSP cases. The new study shows that atlastin interacts physically with DP1 in mammalian cells, and that Sey1p (the yeast atlastin) interacts with the DP1 analog in yeast.

Finally, Dr. Blackstone's study notes that Arabidopsis has an analog of atlastin, called Root Hair Defective 3 (RHD3). Mutations affecting RHD3 cause the plant to grow short, wavy root hairs.

If this connection between axon growth and root hair growth withstands further study, Arabidopsis could be a useful tool for investigating mechanisms of HSP. Arabidopsis is easy to raise in the lab, and the short root hairs of the RHD3 mutant are easy to observe, compared to the growth defects in atlastin-deficient neurons and yeast. Dr. Blackstone hopes to collaborate with other researchers to initiate a search for genes and compounds that correct root hair development in the RHD3 mutant, which might provide valuable therapeutic insights into HSP.

(HTML version includes photo):

The photo caption is: Top: Rat cortical neurons. Bottom: Arabidopsis roots. Left side shows normal neurons and root hairs. Right side shows the effects of atlastin/RHD3 deficiency, with shortening of both and waviness of root hairs. Neuron images courtesy of Dr. Craig Blackstone, NINDS. Arabidopsis images courtesy of Dr. John Schiefelbein, University of Michigan, Ann Arbor.

Reference: Hu J, Shibata Y, Zhu P-P, Voss C, Rismanchi N, Prinz W, Rapoport TA, and Blackstone C. "A Class of Dynamin-Like GTPases Involved in the Generation of the Tubular ER Network." Cell, Vol. 138, August 7, 2009.

NINDS is the nation's primary supporter of biomedical research on the brain and nervous system. NIDDK conducts and supports basic and clinical research and research training on some of the most common, severe and disabling conditions affecting Americans. The Institute's research interests include: diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition, and obesity; and kidney, urologic and hematologic diseases.

Herpes Simplex II Increases Risk of HIV Regardless of Treatment

Infection with Herpes Simplex II increases the risk of contracting HIV even if the herpes lesions have healed over. This is because an increase in white blood cells remains at the site, even when it it is healed, and HIV uses these white blood cells (CD4+ T cells) to infect the human body. - BRH

SCIENTISTS LEARN WHY EVEN TREATED GENITAL HERPES SORES BOOST THE RISK OF HIV INFECTION

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SCIENTISTS LEARN WHY EVEN TREATED GENITAL HERPES SORES BOOST THE RISK OF HIV INFECTION

New research helps explain why infection with herpes simplex virus-2 (HSV-2), which causes genital herpes, increases the risk for HIV infection even after successful treatment heals the genital skin sores and breaks that often result from HSV-2.

Scientists have uncovered details of an immune-cell environment conducive to HIV infection that persists at the location of HSV-2 genital skin lesions long after they have been treated with oral doses of the drug acyclovir and have healed and the skin appears normal. These findings are published in the advance online edition of Nature Medicine on Aug. 2.

Led by Lawrence Corey, M.D., and Jia Zhu, Ph.D., of the Fred Hutchinson Cancer Research Center and Anna Wald, M.D., M.P.H., of the University of Washington, both in Seattle, the study was funded mainly by the National Institute of Allergy and Infectious Diseases (NIAID) with support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, both part of the National Institutes of Health.

"The findings of this study mark an important step toward understanding why HSV-2 infection increases the risk of acquiring HIV and why acyclovir treatment does not reduce that risk," says NIAID Director Anthony S. Fauci, M.D. "Understanding that even treated HSV-2 infections provide a cellular environment conducive to HIV infection suggests new directions for HIV prevention research, including more powerful anti-HSV therapies and ideally an HSV-2 vaccine."

One of the most common sexually transmitted infections worldwide, HSV-2 is associated with a two- to three-fold increased risk for HIV infection. Some HSV-2-infected people have recurring sores and breaks in genital skin, and it has been hypothesized that these lesions account for the higher risk of HIV acquisition. However, recent clinical trials, including an NIAID-funded study completed last year, demonstrated that successful treatment of such genital herpes lesions with the drug acyclovir does not reduce the risk of HIV infection posed by HSV-2 . The current study sought to understand why this is so and to test an alternative theory.

"We hypothesized that sores and breaks in the skin from HSV-2 are associated with a long-lasting immune response at those locations, and that the response consists of an influx of cells that are a perfect storm for HIV infection," says Dr. Corey, co-director of the Vaccine and Infectious Diseases Institute at The Hutchinson Center and head of the Virology Division in the Department of Laboratory Medicine at the University of Washington. "We believe HIV gains access to these cells mainly through microscopic breaks in the skin that occur during sex."

The research team took biopsies of genital skin tissue from eight HIV-negative men and women who were infected with HSV-2. These biopsies were taken at multiple time points: when the patients had genital herpes sores and breaks in the skin, when these lesions had healed, and at two, four and eight weeks after healing. The researchers also took biopsies from four of the patients when herpes lesions reappeared and the patients underwent treatment with oral acyclovir. The scientists continued to take biopsies at regular intervals for 20 weeks after the lesions had healed. For comparison, the investigators also took biopsies from genital tissue that did not have herpes lesions from the same patients.

Previous research has demonstrated that immune cells involved in the body's response to infection remain at the site of genital herpes lesions even after they have healed. The scientists conducting the current study made several important findings about the nature of these immune cells. First, they found that CD4+ T cells-the cells that HIV primarily infects-populate tissue at the sites of healed genital HSV-2 lesions at concentrations 2 to 37 times greater than in unaffected genital skin. Treatment with acyclovir did not reduce this long-lasting, high concentration of HSV-2-specific CD4+ T cells at the sites of healed herpes lesions.

Second, the scientists discovered that a significant proportion of these CD4+ T cells carried CCR5 or CXCR4, the cell-surface proteins that HIV uses (in addition to CD4+ T cells) to enter cells. The percentage of CD4+ T cells expressing CCR5 during acute HSV-2 infection and after healing of genital sores was twice as high in biopsies from the sites of these sores as from unaffected control skin. Moreover, the level of CCR5 expression in CD4+ T cells at the sites of healed genital herpes lesions was similar for patients who had been treated with acyclovir as for those who had not.

Third, the scientists found a significantly higher concentration of immune cells called dendritic cells with the surface protein called DC-SIGN at the sites of healed genital herpes lesions than in control tissue, whether or not the patient was treated with acyclovir. Dendritic cells with DC-SIGN ferry HIV particles to CD4+ T cells, which the virus infects. The DC-SIGN cells often were near CD4+ T cells at the sites of healed lesions-an ideal scenario for the rapid spread of HIV infection.

Finally, using biopsies from two study participants, the scientists found laboratory evidence that HIV replicates three to five times as quickly in cultured tissue from the sites of healed HSV-2 lesions than in cultured tissue from control sites.

All four of these findings help explain why people infected with HSV-2 are at greater risk of acquiring HIV than people who are not infected with HSV-2, even after successful acyclovir treatment of genital lesions.

"HSV-2 infection provides a wide surface area and long duration of time for allowing HIV access to more target cells, providing a greater chance for the initial 'spark' of infection," the authors write. This spark likely ignites once HIV penetrates tiny breaks in genital skin that commonly occur during sex. "Additionally," the authors continue, "the close proximity to DC-SIGN-expressing DCs [dendritic cells] is likely to fuel these embers and provide a mechanism for more efficient localized spread of initial infection." The investigators conclude that reducing the HSV-2-associated risk of HIV infection will require diminishing or eliminating the long-lived immune-cell environment created by HSV-2 infection in the genital tract, ideally through an HSV vaccine. Further, they hypothesize that other sexually transmitted infections (STIs) may create similar cellular environments conducive to HIV infection, explaining why STIs in general are a risk factor for acquiring HIV.

For more information about HIV/AIDS research, go to , and for more information about HSV-2 research, go to .

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 .

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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REFERENCES:

J Zhu et al. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nature Medicine DOI: 10.1038/nm2006 (2009).

C Celum et al. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet DOI: 10.1016/S0140-6736(08)60920-4 (2008).

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.National Institute of Health, National Institute of Allergy and Infectious Disease, Lawrence Corey, Infectious disease, HIV, Clinical trial, Fred Hutchinson Cancer Research Center, University of Washington

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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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 .

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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