JAMA news releases are made available to the public after 3 pm US Central time on the first 4 Tuesdays of each month. The Archives Journals news releases are made available to the public after 3 pm Central time on Mondays. We also provide a list of previous news releases.
THIS WEEK'S CONTENT
JAMA NEWS RELEASES
(Embargoed for Release: 3:00 p.m. CT, Tuesday, September 26, 2006)
JAMA NEWS RELEASES
PREDICTION MODELS HELP IDENTIFY INCREASED RISK OF GENE MUTATION LINKED WITH COLORECTAL CANCER
USE OF ANTIBIOTIC TO TREAT INFECTIOUS EYE DISEASE TRACHOMA MAY INCREASE RISK FOR RE-INFECTION
HIV MEASUREMENT APPEARS TO BE LESS RELIABLE THAN GENERALLY THOUGHT IN PREDICTING LOSS OF CELLS THAT REGULATE IMMUNE RESPONSE
JAMA REPORT (VIDEO SCRIPT)
VIDEO: Windows Media | Quicktime
WEB-BASED PROGRAM CAN HELP PREDICT RISK OF GENETIC PREDISPOSITION TO COLON CANCER
INFORMATION CONTAINED IN THESE NEWS RELEASES IS PROTECTED BY COPYRIGHT. JOURNAL ATTRIBUTION IS REQUIRED.
TV Note: This week's JAMA Report video is on the prediction of gene mutations linked to colorectal cancer. The report will be fed Tuesday, September 26, from 9:00 - 9:30 a.m. ET and 2:00 - 2:30 p.m. ET, on Intelsat America 6 (formerly Telstar 6), Transponder 11 (C-Band), Downlink Freq: 3920 MHz Vertical, Audio: 6.20/6.80. For more information, call 312/464-JAMA.
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Embargoed for Release: 3:00 p.m. CT, Tuesday, September 26, 2006
Media Advisory: To contact the corresponding author of the first study, Sapna Syngal, M.D., M.P.H., call Janet Haley Dubow at 617-632-5665. To contact Sining Chen, Ph.D., call Kenna Lowe at 410-614-6029. To contact editorial co-author James M. Ford, M.D., call Amy Adams at 650-723-3900.
PREDICTION MODELS HELP IDENTIFY INCREASED RISK OF GENE MUTATION LINKED WITH COLORECTAL CANCER
CHICAGO—Prediction models that incorporate certain personal and family medical history characteristics can help identify high-risk patients who are likely to have a gene mutation associated with a type of colorectal cancer, according to two studies in the September 27 issue of JAMA.
Lynch syndrome (also called hereditary nonpolyposis colorectal cancer) is the most common hereditary colorectal cancer syndrome in Western countries, accounting for 2 percent to 5 percent of all colorectal cancers (CRCs). Lynch syndrome is primarily associated with mutations in the MLH1 and MSH2 genes. In hereditary breast-ovarian cancer syndrome, multiple models have been developed to predict mutations in the BRCA1 and BRCA2 genes, and these models are widely implemented by health care professionals as they assess their patients’ genetic risk. For Lynch syndrome, the relative importance of specific aspects of personal and family medical history remains unclear.
Judith Balmana, M.D., formerly of the Dana-Farber Cancer Institute, Boston, and colleagues obtained data from 1,914 individuals undergoing genetic testing of MLH1 and MSH2 and developed a clinical model, the PREMM1,2 (Prediction of Mutations in MLH1 and MSH2) to predict the presence of mutations in the MLH1 and MSH2 genes based on personal and family medical history. A model was developed in an initial group of 898 individuals and subsequently validated in 1,016 patients.
Overall, 14.5 percent (130/898) of the study individuals were found to have mutations: 6.5 percent had mutations in MLH1 and 8.0 percent had mutations in MSH2. In the validation cohort, the overall prevalence of mutations was 15.3 percent. Mutations were particularly prevalent among probands (a patient who is the initial member of a family to come under study) with 2 or more separate CRCs, endometrial cancer, other Lynch syndrome–associated cancers, and multiple diagnoses. The prevalence of mutations in the probands increased with increasing numbers of first-degree relatives with CRC or endometrial cancer. Probands with mutations had a younger average age at CRC diagnosis than those who did not have mutations, and the age at diagnosis of CRC and endometrial cancer was also younger among the relatives of probands with mutations.
“How these risks are translated into clinical decision making depends on a variety of factors, including the availability of comprehensive genetic testing services (sequencing and large rearrangement analysis), the timelines of testing information for clinical management decisions, insurance coverage for testing, and the availability of tissue for analysis. Based on the risk estimate generated from the model and the above factors, a clinician may choose whether genetic evaluation should be pursued, as well as the approach to testing …” the authors write.
“Our prediction rule includes specific and discrete variables and does not rely on complex combinations of diagnoses across generations. The PREMM1,2 model has been externally validated and is available as a user-friendly Web-based model to provide clinicians with an objective tool to estimate the likelihood of finding mutations in the MLH1 and MSH2 genes and to help guide the strategy for molecular evaluation,” the researchers conclude.
(JAMA. 2006;296:1469-1478. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Dr. Balmana is currently with the Universitat Autonoma Barcelona, Spain. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
MODEL HELPS PREDICT RISK OF DEVELOPING COLORECTAL CANCER
In a related study, investigators used family medical history and tumor information to develop another model to predict genetic risk for colorectal or endometrial cancer, according to an article in the September 27 issue of JAMA.
Sining Chen, Ph.D., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues conducted a study to develop a genetic counseling and risk prediction tool to estimate the probability of carrying a mutation in mismatch repair (MMR; a system within the cell for correcting errors in DNA) genes MLH1, MSH2, or MSH6, and the probability of developing colorectal or endometrial cancer. The researchers developed MMRpro, a model that estimates probability based on family history of colorectal and endometrial cancer. External validation of the MMRpro model was conducted on 279 individuals from 226 clinic-based families in the United States, Canada, and Australia (between 1993-2005). All individuals were screened extensively for MLH1 and MSH2 mutations.
“MMRpro predicted the presence of approximately 129 mutations. This shows a close correspondence (calibration) with the observed 121 mutations (ratio of observed to expected results, 0.94),” the authors write. “This results in higher accuracy than existing alternatives and current clinical guidelines.”
“This article introduces MMRpro, a model for prediction of genetic susceptibility in the Lynch syndrome, which makes efficient use of family history and tumor information and provides individualized evaluations. Because model-based prediction algorithms are increasingly used in genetic counseling and prevention activities, MMRpro is a timely tool for identifying and counseling families at risk for the Lynch syndrome and can improve current genetic counseling and early detection practice.”
(JAMA. 2006;296:1479-1487. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
EDITORIAL: PREDICTING AND PREVENTING HEREDITARY COLORECTAL CANCER
In an accompanying editorial, James M. Ford, M.D., and Alice S. Whittemore, Ph.D., of the Stanford University School of Medicine, Stanford, Calif., comment on the studies in this week’s JAMA concerning the development of predictive models for colorectal cancer.
“In summary, these prediction rules should form very useful tools for clinicians and their patients, as well as for epidemiologists who wish to assess both the magnitude of the hereditary nonpolyposis colorectal cancer problem and the potential usefulness of preventive efforts. What are the next steps? Evaluation of all [these] rules using a single data set would be helpful and allow for a direct comparison of the models. Studies using population-based data would be preferable, to assess the performance of the rule among individuals with little or no family history of the Lynch syndrome malignancies. Since the rules were developed and evaluated using samples primarily composed of white individuals with European ancestry, there also is great need to evaluate the performances of these rules when applied to ethnic minorities, as the prevalence and penetrance of Lynch syndrome is poorly understood in nonwhite populations,” they write.
(JAMA. 2006;296:1521-1523. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Financial disclosures – none reported.
For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: mediarelations{at}jama-archives.org.
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Embargoed for Release: 3:00 p.m. CT, Tuesday, September 26, 2006
Media Advisory: To contact corresponding author Deborah Dean, M.D., M.P.H., call Venita Robinson at 510-428-3069.
USE OF ANTIBIOTIC TO TREAT INFECTIOUS EYE DISEASE TRACHOMA MAY INCREASE RISK FOR RE-INFECTION
CHICAGO—Use of the antibiotic azithromycin to treat trachoma in Vietnam resulted in an increase in the risk of re-infections, according to a study in the September 27 issue of JAMA.
In 1995, the World Health Organization (WHO) first published data on global blindness and reported that 15 percent of cases were due to trachoma (a contagious bacterial eye disease in which scar tissue forms inside the eyelid and causes infection), making it the second major cause of blindness after cataract. At that time, the WHO estimated that 146 million individuals were in need of treatment for active trachoma to prevent blindness, 10 million were in need of surgery for trachomatous trichiasis (eyelash[es] touching the eye), and 8 million were already blind, according to background information in the article.
In 1996, the WHO designed the SAFE (Surgery for trachomatous trichiasis; Antibiotics for Chlamydia trachomatis (a type of Chlamydia that causes trachoma); Facial cleanliness; and Environmental improvement) strategy with the goal of elimination of blinding trachoma by the year 2020. For the antibiotic arm of the SAFE strategy, the WHO has recommended antibiotic treatment with either topical tetracycline or oral azithromycin for certain categories of patients with active trachoma. Oral azithromycin has become the drug of choice for the SAFE programs because of difficulties concerning administration and adherence with topical tetracycline eye ointment. Despite a number of studies, there has been a lack of sufficient follow-up beyond the final treatment point to determine rates of recurrence of disease and infection and the risk factors that may contribute to each.
Berna Atik, M.D., M.P.H., of Children’s Hospital Oakland Research Institute, Oakland, Calif., and colleagues evaluated the effect of targeted oral azithromycin treatment of school age children and their household members in Vietnam on active trachoma and C trachomatis infection rates. Vietnam is 1 of 16 priority countries in which the SAFE program has been launched. Three communes, which included 3,186 individuals, were randomly selected in Vietnam for the study that was conducted from November 2000 through November 2003. Azithromycin was given to children from 5 through 15 years of age with active trachoma and their household members in SAFE and SA communes at baseline and 12 months over 2 consecutive years with follow-up for 2 years beyond the last treatment. These communes were compared with a S-only control commune that did not receive azithromycin targeted treatment.
The researchers found that re-infection rates increased significantly between 12 and 36 months for SAFE (from 1.6 to 29.3 per 1,000) and SA (5.1 to 25.3 per 1,000) communes but not for the S-only commune (13.4 to 6.7 per 1,000) after 24 months. Compared with the S-only commune, analysis showed that re-infection risk was about four times higher for SAFE and SA communes at 36 months.
“Collectively, the data are consistent with the hypothesis that systemic azithromycin treatment may interrupt the duration of infection, interfering with host immune responses and, thereby, increase the number of individuals who are susceptible to C trachomatis re-infection. … The strategy of targeting only active trachoma for treatment is likely to be ineffective for long-term trachoma control and may adversely affect disease prevalence over time. While the ‘F’ and ‘E’ components of the SAFE program will need to be evaluated for their efficacy in decreasing rates of active trachoma and infection, a vaccine will likely be needed for long-term control,” the authors write.
(JAMA. 2006;296:1488-1497. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: This work was supported by an International Trachoma Initiative grant and Public Health Service grant from the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: mediarelations{at}jama-archives.org.
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Embargoed for Release: 3:00 p.m. CT, Tuesday, September 26, 2006
Media Advisory: To contact Benigno Rodríguez, M.D., call Susan Licate at 216-368-3635. To contact editorial co-author W. Keith Henry, M.D., call Sarah Buss at 612-624-2449.
HIV MEASUREMENT APPEARS TO BE LESS RELIABLE THAN GENERALLY THOUGHT IN PREDICTING LOSS OF CELLS THAT REGULATE IMMUNE RESPONSE
CHICAGO—Preliminary research indicates that the initial HIV RNA level in untreated HIV-infected patients appears to have little value in predicting the rate of CD4 cell count decrease, potentially limiting its clinical value concerning the decision of when to begin antiretroviral therapy in an individual, according to a study in the September 27 issue of JAMA.
Depletion of CD4 cells is a characteristic of progressive human immunodeficiency virus (HIV) disease and a powerful predictor of the short-term risk of progression to AIDS, according to background information in the article. Blood levels of HIV are also thought to predict HIV disease progression risk. In addition to their role as predictors of the clinical outcomes of HIV infection, CD4 cell count and plasma HIV RNA level are commonly used as markers of the success of highly active antiretroviral therapy (HAART). Until this study was completed, however, the degree to which blood levels of HIV could predict the rate of CD4 cell loss in HIV-infected individuals with similar demographic characteristics to those seen in clinical practice was unclear.
To address this question, Benigno Rodríguez, M.D., of Case Western Reserve University, Cleveland, and colleagues conducted a study to estimate the extent to which presenting blood levels of HIV can account for or “explain” the rate at which CD4 cells are depleted among an untreated HIV-infected population of patients including women and ethnic minorities. The study included repeated analyses of 2 multicenter groups, with observations beginning in May 1984 and ending in August 2004. Analyses were conducted between August 2004 and March 2006. The participants included antiretroviral treatment–naïve, chronically HIV-infected persons (n = 1,289 and n = 1,512 for each of the 2 groups) who were untreated during the observation period (6 months or greater) and with at least 1 HIV RNA level and 2 CD4 cell counts available. Approximately 35 percent were nonwhite, and 35 percent had risk factors other than male-to-male sexual contact.
The researchers found that only a small proportion of the rate at which CD4 cells are lost (only 4 percent - 6 percent) in a given individual patient could be explained by presenting plasma HIV RNA level, suggesting that in chronic untreated HIV infection over 90 percent of the determinants of CD4 cell decline are not reflected in the amount of virus in blood at the time of initial medical evaluation.
“Our findings confirm previous observations that the magnitude of HIV viremia [the presence of a virus in the blood stream], as defined by broad categories of presenting HIV RNA level, is associated with the rate of CD4 cell loss and extend this observation to patient populations comprising both men and women. Despite this association, however, only a small proportion of the interindividual variability in the rate of CD4 cell decline can be explained by plasma HIV RNA level, even after accounting for the effect of measurement error,” the authors write.
“These findings represent a major departure from the notion that plasma HIV RNA level is a reliable predictor of rate of CD4 cell loss in HIV infection and challenge the concept that the magnitude of viral replication (at least as reflected by plasma levels) is the main determinant of the speed of CD4 cell loss at the individual level. The clinical implications are that in the majority of cases, an individual patient’s plasma HIV RNA level at the time of presentation for clinical care cannot predict, to a significant extent, the rate of CD4 cell decline that he or she will experience over the subsequent years and is therefore of limited clinical value in shaping the decision to initiate antiretroviral therapy,” the researchers write.
(JAMA. 2006;296:1498-1506. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: This work was supported in part by the Case Western Reserve University Center for AIDS Research and NIH grants. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
EDITORIAL: EXPLAINING, PREDICTING, AND TREATING HIV-ASSOCIATED CD4 LOSS—AFTER 25 YEARS STILL A PUZZLE
CHICAGO—In an accompanying editorial, W. Keith Henry, M.D., of the University of Minnesota, Minneapolis; Pablo Tebas, M.D., of the University of Pennsylvania, Philadelphia; and H. Clifford Lane, M.D., of the National Institute of Allergy and Infectious Diseases, Bethesda, Md., discuss the findings concerning HIV RNA levels and CD4 cell loss.
“The study by Rodriguez et al may have several important clinical implications. The first and more straightforward is that baseline measurements of viral load alone should have less of a role in driving decisions on when to start antiretroviral therapy for an individual patient; these initial viral load levels cannot predict how rapidly the disease will progress. … The seemingly useful practice of combining a CD4 cell count and plasma HIV RNA levels to assess an individual patient’s prognosis for AIDS progression or response to highly active antiretroviral therapy needs reexamination.”
“The second and potentially more exciting implication of the findings of Rodriguez et al is that future improvements in the treatment of HIV infection and AIDS may result from improved understanding of the 90 percent of CD4 cell depletion that remains enigmatic,” they write. “A better understanding of the immunologic and genetic factors that drive HIV-associated CD4 cell loss may translate to novel therapeutic approaches that could favorably shift the pathogen-host balance. … Discovering and developing therapies that target key nonviral factors has the potential over the decades ahead to build on the success of antiretroviral therapy and expand access to sustainable effective therapy.”
(JAMA. 2006;296:1523-1525. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Please see the editorial for financial disclosures, funding and support, etc.
For More Information: Contact the JAMA/Archives Media Relations Department at 312/464-JAMA (5262) or email: mediarelations{at}jama-archives.org.
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JAMA REPORTS
VIDEO: Windows Media | Quicktime
WEB-BASED PROGRAM CAN HELP PREDICT RISK OF GENETIC PREDISPOSITION TO COLON CANCER
VIDEO:
B-ROLL
Katherine Schneider walking down hall
AUDIO:
GENETIC COUNSELOR KATHERINE SCHNEIDER HELPS PEOPLE FIND OUT ABOUT, AND DEAL WITH, THEIR RISK OF CANCER.
VIDEO:
SOT/FULL
@ :08
Super: Katherine Schneider, M.P.H., C.G.C.
Genetic Counselor
Runs :08
AUDIO:
“These two genes right here, and that explains 80% of the families like yours with so much colon cancer.”
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Katherine’s book showing genes
File of colon cancer
Person having blood taken
AUDIO:
IF THOSE GENES HAVE A MUTATION, OR FORM INCORRECTLY, THEY CAN LEAD TO COLON CANCER. BUT HOW DO YOU KNOW IF YOU SHOULD GET THE BLOOD TEST THAT TELLS YOU IF YOU HAVE A GENETIC RISK OF COLON CANCER?
VIDEO:
SOT/FULL
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Super: Sapna Syngal, M.D., M.P.H.
Dana-Farber Cancer Institute
Runs :11
AUDIO:
“This is a new tool that hopefully will make it much easier for doctors and their patients to figure out if somebody’s at genetic risk for colon cancer or not.”
VIDEO:
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Dr. Syngal at her desk
Exterior Dana-Farber Cancer Institute
Web site
GFX/JAMA COVER
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THIS IS DR. SAPNA (SAP-na) SYNGAL (single) OF DANA-FARBER CANCER INSTITUTE AND BRIGHAM AND WOMEN’S HOSPITAL IN BOSTON. SHE AND COLLEAGUES CREATED A WEB-BASED QUESTIONNAIRE, AND TESTED IT FOR ACCURACY. THEIR FINDINGS APPEAR IN JAMA, THE JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION.
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Sapna Syngal, M.D., M.P.H.
Dana-Farber Cancer Institute
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AUDIO:
“You get the patient and their doctor to fill out a series of questions that are pretty straightforward and then get a number that tells them, well do you have a high likelihood of carrying a mutation or don’t you.”
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Questions on web site
Lab techs testing blood
AUDIO:
THE QUESTIONS ARE ABOUT PERSONAL AND FAMILY HEALTH HISTORY. YOUR SCORE TELLS YOU IF YOU SHOULD CONSIDER GETTING A BLOOD TEST TO CONFIRM YOUR GENETIC RISK.
VIDEO:
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Sapna Syngal, M.D., M.P.H.
Dana-Farber Cancer Institute
Runs :16
AUDIO:
“The risks of developing cancer if you carry a mutation in one of these genes are extraordinarily high. The risk of developing colon cancer is 60 to 80% and for a woman, the risk of developing uterine cancer is about 40 to 60 %.”
VIDEO:
B-ROLL
Colon cancer images
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AND YOUR FAMILY MEMBERS COULD BE AT INCREASED RISK AS WELL. THAT SOUNDS SCARY, BUT LISTEN TO THIS.
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Sapna Syngal, M.D., M.P.H.
Dana-Farber Cancer Institute
Runs :08
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“The genetic test doesn’t mean that you’re going to get cancer, it just means that you’re at risk for cancer and hopefully with this information we’ll be able to prevent cancer from ever happening.”
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Katherine with client
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GENETIC COUNSELOR KATHERINE SCHNEIDER AGREES.
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Katherine Schneider, M.P.H., C.G.C.
Genetic Counselor
Runs :12
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“Cancer is curable if you catch it early and even better, with colonoscopies you can often catch things before they even become cancerous so you’ve actually prevented a cancer.”
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Colon cancer image
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THIS IS MAVIS PRALL WITH THE JAMA REPORT.
