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Research Team at Johns Hopkins Finds Genetic Marker For Crohn’s Disease
| Author: Tony Cappasso |
| Article Date: 5/2/2008 |
Researchers at Johns Hopkins University and at a consortium of other universities have identified new genetic links for Crohn’s disease. The research also indicates that some people of Jewish descent are more likely to develop the illness.
The study examined changes in DNA associated with the two most common forms of inflammatory bowel disease (IBD): Crohn’s Disease (CD), which is most frequently marked by inflammation of the final section of the small bowel (ileum) and parts of the colon, and ulcerative colitis (UC), an inflammation of the internal lining of the rectum and colon.
Results of the study, published in this month’s edition of Genes and Immunity, included information gleaned from 993 families with IBD, 244 of whom were Ashkenazi Jews. Up to 30 percent of people with IBD in the United States are estimated to have a family history of the condition, and about 25 percent of these families have both CD and UC in the family. People of Ashkenazi Jewish descent are at least twice as likely to develop a form of IBD and are more likely to have familial disease.
The scientists analyzed common DNA variations know as single nucleotide polymorphisms or SNPs and found evidence for genes specific to Ashkenazi Jewish families in the study. The genes were on areas of chromosomes one and three. But they also spotted a region of chromosome 13 that had never before been identified with the illness and was shared by Jewish and non-Jewish families. They also noted regions on chromosomes two and 19 that also appeared in both Jews and non-Jews, the research team said.
“What makes these results especially significant is not only the large sample size but also the method we used for screening, namely the use of a high-density, single-nucleotide polymorphism genome-wide linkage process, says Johns Hopkins gastroenterologist and genetic investigator Steven R. Brant, M.D., senior author of the study.
” The new process is 10 times faster than older methods at searching the number of variations across the genome,” he added.
Brant says the study findings go a long way to explaining why members of some Ashkenazi Jewish families were twice as likely to come down with the disorder.
The National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Diseases Genetics Consortium (NIDDK-IBDGC) that organized the study is a multi-center team of American and Canadian investigators established in 2002 to examine genetic links among IBD pedigrees.
The subjects were recruited through the six IBD genetic research centers of the NIDDK-IBDGC -- Cedars-Sinai Hospital in Los Angeles, Johns Hopkins Hospital, the University of Chicago, the University of Montreal, the University of Pittsburgh and the University of Toronto.
Brant says more research is needed to identify the exact genes involved but that researchers know now that they are in the “right neighborhood.”
Source: Johns Hopkins University Bloomberg School of Public Health, Mar. 26, 2008
Physicians at Stamford University School of Medicine say they are developing a new method for early detection of colon cancer. Instead of colonoscopy and biopsy, their method depends on using a special protein that sticks to cancer cells at a stage so early it precedes polyp formation.
The imaging technology is one new way of imaging cancer in the body in real time, says Christopher Contag, Ph.D., associate professor of pediatrics and of microbiology and of immunology, who led the study. Contag says he hopes it might be one of the first to be used routinely for early detection of cancer.
Colon cancer is the third most common cancer in men and women, with about 150,000 people diagnosed each year. Although colonoscopy isn’t perfect, it’s currently the best way of finding colon cancers when they are still at the most treatable stage.
If doctors find suspicious growths during a routine colonoscopy, they take a sample, called a biopsy, and send it to a pathology lab to screen for cancer. That step takes time and not all people have ready access to a nearby pathologist. What’s more, they biopsy only the cancers that form easily visible growths called polyps. Early stage cancers that remain flat aren’t detected.
The trick to picking up cancer without a biopsy is to find a way of seeing which cells are cancerous while they are still in the body. That’s what Contag and his group succeeded in doing.
They found a short protein that sticks to colon cells in the early stages of cancer. Before screening a person, they spray the protein attached to a fluorescent beacon into the colon. The protein then attaches onto any cancerous cells and creates an easily visible fluorescent patch. Contag and his colleagues used a miniaturized microscope to image the colon.
The fluorescent protein highlighted the cancer cells so effectively the researchers could see individual cancer cells. That fine resolution could allow doctors to pick up the earliest possible cancers. It could also become a useful research tool for studying the small number of cancer stem cells that are thought to establish the eventual tumor, he says.
In the initial trial with 15 patients, the technique detected 82 percent of the polyps that were considered cancerous by a pathologist. Contag says his next step is to work with some of the additional small proteins they’ve found that also attach to cancerous cells. He thinks that a combination of those proteins will make the technique highly accurate. The technique could also be used for cancer screening in other areas of the body, he says.
Source: Stamford University School of Medicine, Mar. 16, 2008.
The study examined changes in DNA associated with the two most common forms of inflammatory bowel disease (IBD): Crohn’s Disease (CD), which is most frequently marked by inflammation of the final section of the small bowel (ileum) and parts of the colon, and ulcerative colitis (UC), an inflammation of the internal lining of the rectum and colon.
Results of the study, published in this month’s edition of Genes and Immunity, included information gleaned from 993 families with IBD, 244 of whom were Ashkenazi Jews. Up to 30 percent of people with IBD in the United States are estimated to have a family history of the condition, and about 25 percent of these families have both CD and UC in the family. People of Ashkenazi Jewish descent are at least twice as likely to develop a form of IBD and are more likely to have familial disease.
The scientists analyzed common DNA variations know as single nucleotide polymorphisms or SNPs and found evidence for genes specific to Ashkenazi Jewish families in the study. The genes were on areas of chromosomes one and three. But they also spotted a region of chromosome 13 that had never before been identified with the illness and was shared by Jewish and non-Jewish families. They also noted regions on chromosomes two and 19 that also appeared in both Jews and non-Jews, the research team said.
“What makes these results especially significant is not only the large sample size but also the method we used for screening, namely the use of a high-density, single-nucleotide polymorphism genome-wide linkage process, says Johns Hopkins gastroenterologist and genetic investigator Steven R. Brant, M.D., senior author of the study.
” The new process is 10 times faster than older methods at searching the number of variations across the genome,” he added.
Brant says the study findings go a long way to explaining why members of some Ashkenazi Jewish families were twice as likely to come down with the disorder.
The National Institute of Diabetes and Digestive and Kidney Diseases Inflammatory Bowel Diseases Genetics Consortium (NIDDK-IBDGC) that organized the study is a multi-center team of American and Canadian investigators established in 2002 to examine genetic links among IBD pedigrees.
The subjects were recruited through the six IBD genetic research centers of the NIDDK-IBDGC -- Cedars-Sinai Hospital in Los Angeles, Johns Hopkins Hospital, the University of Chicago, the University of Montreal, the University of Pittsburgh and the University of Toronto.
Brant says more research is needed to identify the exact genes involved but that researchers know now that they are in the “right neighborhood.”
Source: Johns Hopkins University Bloomberg School of Public Health, Mar. 26, 2008
Physicians at Stamford University School of Medicine say they are developing a new method for early detection of colon cancer. Instead of colonoscopy and biopsy, their method depends on using a special protein that sticks to cancer cells at a stage so early it precedes polyp formation.
The imaging technology is one new way of imaging cancer in the body in real time, says Christopher Contag, Ph.D., associate professor of pediatrics and of microbiology and of immunology, who led the study. Contag says he hopes it might be one of the first to be used routinely for early detection of cancer.
Colon cancer is the third most common cancer in men and women, with about 150,000 people diagnosed each year. Although colonoscopy isn’t perfect, it’s currently the best way of finding colon cancers when they are still at the most treatable stage.
If doctors find suspicious growths during a routine colonoscopy, they take a sample, called a biopsy, and send it to a pathology lab to screen for cancer. That step takes time and not all people have ready access to a nearby pathologist. What’s more, they biopsy only the cancers that form easily visible growths called polyps. Early stage cancers that remain flat aren’t detected.
The trick to picking up cancer without a biopsy is to find a way of seeing which cells are cancerous while they are still in the body. That’s what Contag and his group succeeded in doing.
They found a short protein that sticks to colon cells in the early stages of cancer. Before screening a person, they spray the protein attached to a fluorescent beacon into the colon. The protein then attaches onto any cancerous cells and creates an easily visible fluorescent patch. Contag and his colleagues used a miniaturized microscope to image the colon.
The fluorescent protein highlighted the cancer cells so effectively the researchers could see individual cancer cells. That fine resolution could allow doctors to pick up the earliest possible cancers. It could also become a useful research tool for studying the small number of cancer stem cells that are thought to establish the eventual tumor, he says.
In the initial trial with 15 patients, the technique detected 82 percent of the polyps that were considered cancerous by a pathologist. Contag says his next step is to work with some of the additional small proteins they’ve found that also attach to cancerous cells. He thinks that a combination of those proteins will make the technique highly accurate. The technique could also be used for cancer screening in other areas of the body, he says.
Source: Stamford University School of Medicine, Mar. 16, 2008.