Gene Mutations Linked to Crohn’s Disease in Ashkenazi Jews

THURSDAY, March 8 (HealthDay News) — Researchers have identified five new genetic mutations associated with Crohn’s disease in Jews of Eastern European descent (Ashkenazi Jews) and say their findings may help explain why Crohn’s is nearly four times more prevalent in this group than in the general population.

Crohn’s is an inflammatory bowel disease that causes swelling and irritation in the digestive tract. Symptoms include abdominal pain, diarrhea, rectal bleeding, weight loss, and fever.

Previous research pinpointed 71 genetic variants associated with Crohn’s disease risk in people of European ancestry. In this new study, Mount Sinai School of Medicine researchers compared almost 2,000 Ashkenazi Jews with Crohn’s disease to another 4,500 Ashkenazi Jews without the disease.

The team found 12 of the known risk variants and also discovered five new genetic risk regions on chromosomes 5q21.1, 2p15, 8q21.11, 10q26.3 and 11q12.1.

“This is the largest study to date, and the first to discover the unique risk factors of Crohn’s disease in the Ashkenazi Jewish population,” study leader Inga Peter, an associate professor of genetics and genomic sciences, said in a Mount Sinai news release.

“The prevalence of this disease is so much higher in Ashkenazi Jews, and the involvement of genetic variants predominant in this population might help understand why that is,” she added.

The researchers also found that the genetic structure of the newly-identified regions associated with Crohn’s disease risk in Ashkenazi Jews was much less diverse than that of non-Jewish Europeans.

“Not only did we discover different risk factors for Ashkenazi Jews, but we found that some previously known risk factors are more potent to this population,” Peter said. “Armed with this new information, we can begin to analyze the specific signals in order to pinpoint causal genetic mutations, discover why they are malfunctioning, and eventually develop novel treatment approaches.”

The study is published March 8 in the online edition of PLoS Genetics.

More information

The U.S. National Institute of Diabetes and Digestive and Kidney Diseases has more about Crohn’s disease.

View the original article here

Leukemia gene mutations linked to survival odds

(Reuters) – Advances in genetic profiling are paving the way for more precise, and effective, treatment of the aggressive bone marrow cancer known as acute mylogenous leukemia, or AML, according to new research.

Two studies, published in the latest edition of the New England Journal of Medicine, show that genetic testing can guide doctors in how best to use current therapies as well as identify new drug targets.

“As lots of studies identify new alterations in genes in leukemia and other cancers, we need to begin to understand how these alterations in DNA can predict outcomes and determine differences in treatment,” said Dr. Ross Levine of Memorial Sloan-Kettering Cancer Center in New York, the lead author of one of the studies.

Such personalized therapy is considered the new frontier for medical practice, and hopes for its success underpin a $5.7 billion hostile bid by drugmaker Roche Holding for gene sequencing company Illumina.

The second study, from Washington University in St. Louis, found that 85 percent of bone marrow cells in patients with myelodysplastic syndrome, a blood-related disorder that can precede AML, were linked to mutations in progressive cancer.

The Sloan-Kettering study analyzed bone marrow samples from 502 AML patients for mutations in 18 genes associated with the disease. The researchers were able to categorize two-thirds of the patients into groups clearly defined by their survival chances.

The study found that high-dose chemotherapy improved the rate of survival for patients with three specific genetic mutations, compared with standard-dose chemo.

It also showed that genetic profiling makes it possible to more precisely determine which patients are most likely to have their leukemia return after treatment.

AML is typically cured in about 40 percent of adults between the ages of 18 and 60, according to Levine.

“We were able to identify a very large subset of patients who need new therapies,” he said. “Another set was found to do incredibly well with existing therapies, and that is very informative.”

The American Cancer Society estimates that AML will be diagnosed in nearly 14,000 Americans this year and that more than 10,000 people will die from the disease.

Gene profiling for AML, and most other cancers, is not currently part of standard clinical practice.

“There are aspects of this that are ready to be adopted,” Levine said, adding that the immediate hurdles are the cost of genetic testing and intellectual property rights pertaining to genes that have been patented.

And questions remain about the number of genetic mutations that AML patients should be screened for.

“It is exciting to think that the goal of personalized medicine is quickly approaching,” Dr. Lucy Godley said in a NEJM editorial. “But it will require careful thought to implement genomic-based clinical evaluation in a way that is meaningful for patients.”

(Reporting by Deena Beasley; Editing by Michele Gershberg and John Wallace)

View the original article here

Leukemia gene mutations linked to survival odds

(Reuters) – Advances in genetic profiling are paving the way for more precise, and effective, treatment of the aggressive bone marrow cancer known as acute mylogenous leukemia, or AML, according to new research.

Two studies, published in the latest edition of the New England Journal of Medicine, show that genetic testing can guide doctors in how best to use current therapies as well as identify new drug targets.

“As lots of studies identify new alterations in genes in leukemia and other cancers, we need to begin to understand how these alterations in DNA can predict outcomes and determine differences in treatment,” said Dr. Ross Levine of Memorial Sloan-Kettering Cancer Center in New York, the lead author of one of the studies.

Such personalized therapy is considered the new frontier for medical practice, and hopes for its success underpin a $5.7 billion hostile bid by drugmaker Roche Holding for gene sequencing company Illumina.

The second study, from Washington University in St. Louis, found that 85 percent of bone marrow cells in patients with myelodysplastic syndrome, a blood-related disorder that can precede AML, were linked to mutations in progressive cancer.

The Sloan-Kettering study analyzed bone marrow samples from 502 AML patients for mutations in 18 genes associated with the disease. The researchers were able to categorize two-thirds of the patients into groups clearly defined by their survival chances.

The study found that high-dose chemotherapy improved the rate of survival for patients with three specific genetic mutations, compared with standard-dose chemo.

It also showed that genetic profiling makes it possible to more precisely determine which patients are most likely to have their leukemia return after treatment.

AML is typically cured in about 40 percent of adults between the ages of 18 and 60, according to Levine.

“We were able to identify a very large subset of patients who need new therapies,” he said. “Another set was found to do incredibly well with existing therapies, and that is very informative.”

The American Cancer Society estimates that AML will be diagnosed in nearly 14,000 Americans this year and that more than 10,000 people will die from the disease.

Gene profiling for AML, and most other cancers, is not currently part of standard clinical practice.

“There are aspects of this that are ready to be adopted,” Levine said, adding that the immediate hurdles are the cost of genetic testing and intellectual property rights pertaining to genes that have been patented.

And questions remain about the number of genetic mutations that AML patients should be screened for.

“It is exciting to think that the goal of personalized medicine is quickly approaching,” Dr. Lucy Godley said in a NEJM editorial. “But it will require careful thought to implement genomic-based clinical evaluation in a way that is meaningful for patients.”

(Reporting by Deena Beasley; Editing by Michele Gershberg and John Wallace)

View the original article here