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Bellcross C.,National Office of Public Health Genomics | Dotson W.D.,Office of Public Health Genomics
PLoS Currents | Year: 2010

Differences in the expression of specific genes within breast tumors have been associated with risk of recurrence after treatment. Most women with Stage I or II node-negative breast cancer (especially when estrogen-receptor positive and treated with tamoxifen) remain disease-free at 10 years. Information on risk of recurrence could help identify women most likely to benefit from chemotherapy. Several clinically available gene expression profiles (GEP) provide "recurrence risk scores" that are intended to supplement information used by clinicians and patients in treatment decision-making.

Yang Q.,Office of Public Health Genomics | Bailey L.,University of Georgia | Clarke R.,University of Oxford | Flanders W.D.,Emory University | And 4 more authors.
American Journal of Clinical Nutrition | Year: 2012

Background: The association between blood homocysteine concentration and the risk of cardiovascular disease (CVD) remains controversial, but few studies have examined the association between MTHFR C677T (a proxy for high homocysteine concentration) and death from CVD. Objective: The objective was to examine associations of MTHFR C677T, a proxy for high homocysteine concentrations, with CVD mortality and with all-cause mortality in a national representative prospective cohort of the US adult population before the introduction of mandatory folic acid fortification of flour. Design: We used Mendelian randomization to examine the association of MTHFR C677T with cause-specific mortality in 5925 participants by accessing the NHANES III (1991-1994) Linked Mortality File (through 2006). Results: A comparison of homozygotes at baseline showed that individuals with a TT genotype had a 2.2-μmol/L higher homocysteine and a 1.4-ng/mL lower folate concentration, respectively, than did those with a CC genotype. The TT genotype frequency varied from 1.2% (95% CI: 0.7, 2.0) in non-Hispanic blacks and 11.6% (95% CI: 9.6, 14.0) in non-Hispanic whites to 19.4% (95% CI: 16.7, 22.3) in Mexican Americans. After adjustment for ethnic group and other CVD risk factors, the MTHFR C677T TT genotype was associated with significantly lower CVD mortality (HR: 0.69; 95% CI: 0.50, 0. 95) but had no significant effect on all-cause mortality (HR: 0.79; 95% CI: 0.59, 1.05). After stratification by period of followup, the inverse association of MTHFR with CVD mortality was significant only in the period after introduction of mandatory folic acid fortification. Conclusion: The inverse association of MTHFR with CVD mortality was unexpected and highlights the need for caution in interpretation of Mendelian randomization studies, which, like other observational studies, can be influenced by chance, bias, or confounding. © 2012 American Society for Nutrition.

McBride C.M.,National Human Genome Research Institute | Bowen D.,Boston University | Brody L.C.,National Human Genome Research Institute | Condit C.M.,University of Georgia | And 8 more authors.
American Journal of Preventive Medicine | Year: 2010

Despite the quickening momentum of genomic discovery, the communication, behavioral, and social sciences research needed for translating this discovery into public health applications has lagged behind. The National Human Genome Research Institute held a 2-day workshop in October 2008 convening an interdisciplinary group of scientists to recommend forward-looking priorities for translational research. This research agenda would be designed to redress the top three risk factors (tobacco use, poor diet, and physical inactivity) that contribute to the four major chronic diseases (heart disease, type 2 diabetes, lung disease, and many cancers) and account for half of all deaths worldwide. Three priority research areas were identified: (1) improving the public's genetic literacy in order to enhance consumer skills; (2) gauging whether genomic information improves risk communication and adoption of healthier behaviors more than current approaches; and (3) exploring whether genomic discovery in concert with emerging technologies can elucidate new behavioral intervention targets. Important crosscutting themes also were identified, including the need to: (1) anticipate directions of genomic discovery; (2) take an agnostic scientific perspective in framing research questions asking whether genomic discovery adds value to other health promotion efforts; and (3) consider multiple levels of influence and systems that contribute to important public health problems. The priorities and themes offer a framework for a variety of stakeholders, including those who develop priorities for research funding, interdisciplinary teams engaged in genomics research, and policymakers grappling with how to use the products born of genomics research to address public health challenges. © 2010.

Gwinn M.,McKing Consulting Corporation | Dotson W.D.,Office of Public Health Genomics | Khoury M.J.,Office of Public Health Genomics
PLoS Currents | Year: 2010

Evidence on Genomic Tests is an open access publication option for communicating high-quality, scientific information that is needed to evaluate health applications of genomic research. By using Google's knol platform, we aim to reduce conventional barriers to sharing, updating, and accessing the results of knowledge synthesis and to increase the benefits to authors and users alike. Good, fast, and affordable technologies are driving the "genomics revolution" in biomedical research. The Internet serves as an amplifier, rapidly publishing research findings and publicizing them to a wide audience. Public interest in the field has focused on potential health applications, especially genomic tests for predicting, diagnosing, and managing common diseases. Although many such tests are emerging, information on their clinical validity and utility tends to be scattered and incomplete.

Khoury M.J.,Office of Public Health Genomics | Khoury M.J.,U.S. National Cancer Institute | Gwinn M.L.,Office of Public Health Genomics | Glasgow R.E.,U.S. National Cancer Institute | Kramer B.S.,U.S. National Cancer Institute
American Journal of Preventive Medicine | Year: 2012

The term P4 medicine is used to denote an evolving field of medicine that uses systems biology approaches and information technologies to enhance wellness rather than just treat disease. Its four components include predictive, preventive, personalized, and participatory medicine. In the current paper, it is argued that in order to fulfill the promise of P4 medicine, a "fifth P" must be integrated - the population perspective - into each of the other four components. A population perspective integrates predictive medicine into the ecologic model of health; applies principles of population screening to preventive medicine; uses evidence-based practice to personalize medicine; and grounds participatory medicine on the three core functions of public health: assessment, policy development, and assurance. Population sciences - including epidemiology; behavioral, social, and communication sciences; and health economics, implementation science, and outcomes research - are needed to show the value of P4 medicine. Balanced strategies that implement both population- and individual-level interventions can best maximize health benefits, minimize harm, and avoid unnecessary healthcare costs. © 2012 American Journal of Preventive Medicine.

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