【medical-news】阿斯匹林显著降低最具侵袭性的Barrett's食管患者患食管癌的风险
发布于 2007-03-01 · 浏览 1115 · IP 湖北湖北
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Aspirin Significantly Reduces Esophageal-Cancer Risk In People With Most- Aggressive Form Of Barrett's Esophagus
Main Category: Ear, Nose and Throat News
Article Date: 28 Feb 2007 - 0:00 PST
Researchers at Fred Hutchinson Cancer Research Center have found that people with the most-aggressive form of Barrett's esophagus, a precancerous condition that can lead to esophageal cancer, may benefit the most from preventive therapy with aspirin, ibuprofen and other nonsteroidal anti-inflammatory drugs, or NSAIDs. The researchers also identified a cluster of four known cancer biomarkers, or genetic abnormalities, in people with Barrett's that significantly increases their risk of developing esophageal cancer.
These findings, by lead authors Patricia C. Galipeau and Xiaohong Li, senior author Brian J. Reid, M.D., Ph.D., and colleagues in the Hutchinson Center-based Seattle Barrett's Esophagus Program, will be published in the Feb. 27 issue of PLoS Medicine, a freely available online journal. Researchers from Virginia Mason Medical Center, Harvard Medical School and The Wistar Institute collaborated on the study, which was funded by the National Institutes of Health and the Hutchinson Center.
The researchers found that those with three or more of the cancer biomarkers upon enrollment in the study who also used aspirin or other NSAIDs had a 30 percent risk of esophageal cancer after 10 years, while those with the same biomarkers who did not use NSAIDs had a 79 percent risk of developing cancer within a decade of joining the study.
"This is the first prospective, longitudinal study in patients with Barrett's esophagus -- or any other pre-malignant condition, for that matter -- to link somatic genetic biomarkers for cancer-risk prediction with candidate interventions such as NSAIDs to prevent cancer," said Galipeau, a research technician in Reid's laboratory, which is based in the Hutchinson Center's Human Biology Division.
The researchers also found that Barrett's patients whose esophageal tissue had no such genetic abnormalities, or biomarkers, upon joining the study had a 12 percent risk of developing esophageal cancer after 10 years, whereas those with three or more of the abnormalities at baseline had a nearly 80 percent risk of developing such cancer within a decade.
"Several studies have suggested that individual genetic abnormalities may identify Barrett's patients who are at increased risk of progression toward esophageal cancer, but this is the first study to evaluate the combined contribution of genetic abnormalities for esophageal cancer-risk prediction," said Reid, director of the Seattle Barrett's Esophagus Program.
The study followed 243 people with Barrett's esophagus for 10 years (189 male, 54 female, mean age 62 upon joining the study). The participants were interviewed about their medical history, diet and medication use and were closely monitored for signs of disease progression through regular endoscopies and tissue biopsies.
Their Barrett's-related esophageal tissue was evaluated at the initial study visit for a variety of known cancer biomarkers, but the genetic abnormalities that were most strongly predictive of progression toward cancer were:
Loss of heterozygosity (LOH) at 9p and 17p -- loss on the short arms of chromosomes 17 and 9. Such chromosomal abnormalities inactivate tumor- suppressor genes that are critical for controlling cell growth.
DNA content abnormalities (aneuploidy and tetraploidy) -- the accumulation of cells with grossly abnormal amounts of DNA, which indicates substantial genetic damage and heralds advanced progression toward cancer.
Ultimately, the researchers hope, these biomarkers one day could be used in a clinical setting to identify which Barrett's patients are most likely to develop esophageal cancer and therefore benefit from aggressive cancer surveillance via endoscopy and chemoprevention with aspirin and other NSAIDs. Galipeau and colleagues are in the process of developing such a standardized, biomarker-based screening test. The test would evaluate DNA from esophageal- tissue biopsies, but significantly fewer tissue samples would need to be collected as compared to current endoscopic-surveillance methods.
"Once such a test is available, it could be a major factor in guiding the development of clinical trials to identify high-risk patients and definitively determine the value of NSAIDs in preventing the progression of Barrett's esophagus toward cancer," Reid said.
Main Category: Ear, Nose and Throat News
Article Date: 28 Feb 2007 - 0:00 PST
Researchers at Fred Hutchinson Cancer Research Center have found that people with the most-aggressive form of Barrett's esophagus, a precancerous condition that can lead to esophageal cancer, may benefit the most from preventive therapy with aspirin, ibuprofen and other nonsteroidal anti-inflammatory drugs, or NSAIDs. The researchers also identified a cluster of four known cancer biomarkers, or genetic abnormalities, in people with Barrett's that significantly increases their risk of developing esophageal cancer.
These findings, by lead authors Patricia C. Galipeau and Xiaohong Li, senior author Brian J. Reid, M.D., Ph.D., and colleagues in the Hutchinson Center-based Seattle Barrett's Esophagus Program, will be published in the Feb. 27 issue of PLoS Medicine, a freely available online journal. Researchers from Virginia Mason Medical Center, Harvard Medical School and The Wistar Institute collaborated on the study, which was funded by the National Institutes of Health and the Hutchinson Center.
The researchers found that those with three or more of the cancer biomarkers upon enrollment in the study who also used aspirin or other NSAIDs had a 30 percent risk of esophageal cancer after 10 years, while those with the same biomarkers who did not use NSAIDs had a 79 percent risk of developing cancer within a decade of joining the study.
"This is the first prospective, longitudinal study in patients with Barrett's esophagus -- or any other pre-malignant condition, for that matter -- to link somatic genetic biomarkers for cancer-risk prediction with candidate interventions such as NSAIDs to prevent cancer," said Galipeau, a research technician in Reid's laboratory, which is based in the Hutchinson Center's Human Biology Division.
The researchers also found that Barrett's patients whose esophageal tissue had no such genetic abnormalities, or biomarkers, upon joining the study had a 12 percent risk of developing esophageal cancer after 10 years, whereas those with three or more of the abnormalities at baseline had a nearly 80 percent risk of developing such cancer within a decade.
"Several studies have suggested that individual genetic abnormalities may identify Barrett's patients who are at increased risk of progression toward esophageal cancer, but this is the first study to evaluate the combined contribution of genetic abnormalities for esophageal cancer-risk prediction," said Reid, director of the Seattle Barrett's Esophagus Program.
The study followed 243 people with Barrett's esophagus for 10 years (189 male, 54 female, mean age 62 upon joining the study). The participants were interviewed about their medical history, diet and medication use and were closely monitored for signs of disease progression through regular endoscopies and tissue biopsies.
Their Barrett's-related esophageal tissue was evaluated at the initial study visit for a variety of known cancer biomarkers, but the genetic abnormalities that were most strongly predictive of progression toward cancer were:
Loss of heterozygosity (LOH) at 9p and 17p -- loss on the short arms of chromosomes 17 and 9. Such chromosomal abnormalities inactivate tumor- suppressor genes that are critical for controlling cell growth.
DNA content abnormalities (aneuploidy and tetraploidy) -- the accumulation of cells with grossly abnormal amounts of DNA, which indicates substantial genetic damage and heralds advanced progression toward cancer.
Ultimately, the researchers hope, these biomarkers one day could be used in a clinical setting to identify which Barrett's patients are most likely to develop esophageal cancer and therefore benefit from aggressive cancer surveillance via endoscopy and chemoprevention with aspirin and other NSAIDs. Galipeau and colleagues are in the process of developing such a standardized, biomarker-based screening test. The test would evaluate DNA from esophageal- tissue biopsies, but significantly fewer tissue samples would need to be collected as compared to current endoscopic-surveillance methods.
"Once such a test is available, it could be a major factor in guiding the development of clinical trials to identify high-risk patients and definitively determine the value of NSAIDs in preventing the progression of Barrett's esophagus toward cancer," Reid said.
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