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"Precision medicine" disparities

Nikita Wright, Padmashree Rida, Uma Krishnamurti, Xiaoxian Li, Ritu Aneja
African Americans (AAs) are more likely than European Americans to develop aggressive breast cancer subtypes, and have higher recurrence and mortality rates; this results in a stark breast-cancer related ethnic disparity in clinical outcomes. In this era of personalized oncology, companion diagnostics (CDx) are transforming the cancer treatment narrative slowly but steadily, by enabling the use of safety and/or efficacy biomarkers to stratify patient populations, and thus ensuring more effective deployment of targeted therapeutics...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
Juliana M Kling, Steven H Rose, Lisa N Kransdorf, Thomas R Viggiano, Virginia M Miller
BACKGROUND: Addressing healthcare disparities is a national priority for initiatives in precision and individualized medicine. An essential component of precision medicine is the understanding that sex and gender influence health and disease. Whether these issues are addressed in post-graduate medical education curricula is unknown. METHODS: A questionnaire was designed and administered to residents across the Mayo Clinic enterprise to assess current knowledge of sex and gender medicine in a large program of post-graduate medical education and to identify barriers and preferred teaching methods for addressing sex and gender issues in health and disease...
2016: Biology of Sex Differences
Christopher R Friese, Yun Li, Irina Bondarenko, Timothy P Hofer, Kevin C Ward, Ann S Hamilton, Dennis Deapen, Allison W Kurian, Steven J Katz
BACKGROUND: The 21-gene recurrence score (RS) assay stratifies early-stage, estrogen receptor-positive breast cancer by recurrence risk. Few studies have examined the ways in which physicians use the RS to recommend adjuvant systemic chemotherapy or patients' experiences with testing and decision making. METHODS: This study surveyed 3880 women treated for breast cancer in 2013-2014; they were identified from the Los Angeles County and Georgia Surveillance, Epidemiology, and End Results registries (response rate, 71%)...
October 24, 2016: Cancer
Khuthala Mnika, Gift D Pule, Collet Dandara, Ambroise Wonkam
Sickle cell disease (SCD) is a blood disease caused by a single nucleotide substitution (T > A) in the beta globin gene on chromosome 11. The single point mutation (Glu6Val) promotes polymerization of hemoglobin S (HbS) and causes sickling of erythrocytes. Vaso-occlusive painful crises are associated with recurrent and long-term use of analgesics/opioids and hydroxyurea (HU) by people living with SCD. The present analysis offers a state-of-the-art expert review of the effectiveness of pharmacogenomics/genetics of pain management in SCD, with specific focus on HU and opioids...
October 2016: Omics: a Journal of Integrative Biology
Andrea Garofalo, Lynette Sholl, Brendan Reardon, Amaro Taylor-Weiner, Ali Amin-Mansour, Diana Miao, David Liu, Nelly Oliver, Laura MacConaill, Matthew Ducar, Vanesa Rojas-Rudilla, Marios Giannakis, Arezou Ghazani, Stacy Gray, Pasi Janne, Judy Garber, Steve Joffe, Neal Lindeman, Nikhil Wagle, Levi A Garraway, Eliezer M Van Allen
BACKGROUND: The diversity of clinical tumor profiling approaches (small panels to whole exomes with matched or unmatched germline analysis) may engender uncertainty about their benefits and liabilities, particularly in light of reported germline false positives in tumor-only profiling and use of global mutational and/or neoantigen data. The goal of this study was to determine the impact of genomic analysis strategies on error rates and data interpretation across contexts and ancestries...
2016: Genome Medicine
Chanita Hughes Halbert, Jasmine McDonald, Susan Vadaparampil, LaShanta Rice, Melanie Jefferson
IMPORTANCE: Precision medicine is an approach to detecting, treating, and managing disease that is based on individual variation in genetic, environmental, and lifestyle factors. Precision medicine is expected to reduce health disparities, but this will be possible only if studies have adequate representation of racial minorities. OBJECTIVE: It is critical to anticipate the rates at which individuals from diverse populations are likely to participate in precision medicine studies as research initiatives are being developed...
2016: PloS One
Mark Lawler, Declan French, Raymond Henderson, Ajay Aggarwal, Richard Sullivan
In his last two State of the Union addresses, President Barack Obama has focused on the need to deliver innovative solutions to improve human health, through the Precision Medicine Initiative in 2015 and the recently announced Cancer Moonshot in 2016. Precision cancer care has delivered clear patient benefit, but even for high-impact medicines such as imatinib mesylate (Glivec) in chronic myeloid leukaemia, the excitement at the success of this practice-changing clinical intervention has been somewhat tempered by the escalating price of this 'poster child' for precision cancer medicine (PCM)...
2016: Public Health Genomics
Manali I Patel
Over the past decade, scientific advancements have resulted in improved survival from acute leukemia. Continued advancements are expected given the attention to precision medicine and the resulting growth in development and adoption of risk-stratified, personalized therapies. While precision medicine has great potential to improve acute leukemia outcomes, there remain significant barriers to ensuring equitable access to these technologies and receipt of these prescribed targeted, personalized therapies. Over the past 3 years, studies report persistent outcome disparities among patients from specific racial and ethnic backgrounds, insurance and socioeconomic status, and other socio-demographic factors after a diagnosis of acute leukemia...
August 2016: Current Hematologic Malignancy Reports
Marquitta J White, O Risse-Adams, P Goddard, M G Contreras, J Adams, D Hu, C Eng, S S Oh, A Davis, K Meade, E Brigino-Buenaventura, M A LeNoir, K Bibbins-Domingo, M Pino-Yanes, E G Burchard
Asthma, an inflammatory disorder of the airways, is the most common chronic disease of children worldwide. There are significant racial/ethnic disparities in asthma prevalence, morbidity, and mortality among US children. This trend is mirrored in obesity, which may share genetic and environmental risk factors with asthma. The majority of asthma biomedical research has been performed in populations of European decent. We sought to identify genetic risk factors for asthma in African American children. We also assessed the generalizability of genetic variants associated with asthma in European and Asian populations to African American children...
July 2016: Immunogenetics
Evan S Wu, Jong Y Park, Joseph A Zeitouni, Carmen R Gomez, Isildinha M Reis, Wei Zhao, Deukwoo Kwon, Eunkyung Lee, Omar L Nelson, Hui-Yi Lin, Elizabeth J Franzmann, Jason Savell, Thomas V McCaffrey, W Jarrard Goodwin, Jennifer J Hu
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and minorities have the worst survival. However, the molecular mechanisms underlying survival disparities have not been elucidated. METHODS: In a retrospective study, we assessed association between HNSCC early death (<2 years) and 208 somatic mutations of 10 cancer-related genes in 214 patients: 98 non-Hispanic whites (46%), 72 Hispanic whites (34%), and 44 African Americans (20%)...
August 2016: Head & Neck
Timothy Dye, Dongmei Li, Margaret Demment, Susan Groth, Diana Fernandez, Ann Dozier, Jack Chang
BACKGROUND: "Precision medicine" (PM) requires researchers to identify actionable genetic risks and for clinicians to interpret genetic testing results to patients. Whether PM will equally benefit all populations or exacerbate existing disparities is uncertain. METHODS: We ascertained attitudes toward genetic testing and genetic research by race in the United States using the online Amazon mTurk US workforce (n = 403 White; n = 56 African American (AA))...
July 2016: Journal of the American Medical Informatics Association: JAMIA
Taylor S Cohen, Jamese J Hilliard, Omari Jones-Nelson, Ashley E Keller, Terrence O'Day, Christine Tkaczyk, Antonio DiGiandomenico, Melissa Hamilton, Mark Pelletier, Qun Wang, Binh An Diep, Vien T M Le, Lily Cheng, JoAnn Suzich, C Kendall Stover, Bret R Sellman
Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S...
March 9, 2016: Science Translational Medicine
Jessica N Cooke Bailey, Sarah Wilson, Kristin Brown-Gentry, Robert Goodloe, Dana C Crawford
Kidney disease is a well-known health disparity in the United States where African Americans are affected at higher rates compared with other groups such as European Americans and Mexican Americans. Common genetic variants in the myosin, heavy chain 9, non-muscle (MYH9) gene were initially identified as associated with non-diabetic end-stage renal disease in African Americans, and it is now understood that these variants are in strong linkage disequilibrium with likely causal variants in neighboring APOL1. Subsequent genome-wide and candidate gene studies have suggested that MYH9 common variants among others are also associated with chronic kidney disease and quantitative measures of kidney function in various populations...
2016: Pacific Symposium on Biocomputing
Sam Regenbogen, Angela D Wilkins, Olivier Lichtarge
Biomedicine produces copious information it cannot fully exploit. Specifically, there is considerable need to integrate knowledge from disparate studies to discover connections across domains. Here, we used a Collaborative Filtering approach, inspired by online recommendation algorithms, in which non-negative matrix factorization (NMF) predicts interactions among chemicals, genes, and diseases only from pairwise information about their interactions. Our approach, applied to matrices derived from the Comparative Toxicogenomics Database, successfully recovered Chemical-Disease, Chemical-Gene, and Disease-Gene networks in 10-fold cross-validation experiments...
2016: Pacific Symposium on Biocomputing
K Divaris
In recent years, unprecedented gains in the understanding of the biology and mechanisms underlying human health and disease have been made. In the domain of oral health, although much remains to be learned, the complex interactions between different systems in play have begun to unravel: host genome, oral microbiome with its transcriptome, proteome and metabolome, and more distal influences, including relevant behaviors and environmental exposures. A reasonable expectation is that this emerging body of knowledge can help improve the oral health and optimize care for individuals and populations...
March 2016: Journal of Dental Research
Akihiro Nishi, Danny A Milner, Edward L Giovannucci, Reiko Nishihara, Andy S Tan, Ichiro Kawachi, Shuji Ogino
The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology...
2016: Expert Review of Molecular Diagnostics
Barry I Freedman, Arthur H Cohen
Unrelated disease processes commonly occur in non-diabetic individuals with mild-to-moderate hypertension and low level or absent proteinuria who present with chronic kidney disease: primary glomerulosclerosis in those with recent African ancestry, and arteriolar nephrosclerosis with resultant glomerular ischaemia potentially related to hypertension and vascular disease risk factors in other cases. Unfortunately, nephrologists often indiscriminately apply a diagnosis of 'hypertensive nephrosclerosis' to patients in either scenario, which implies that the hypertension is causative of their renal disease...
January 2016: Nature Reviews. Nephrology
Alex H Wagner, Adam C Coffman, Benjamin J Ainscough, Nicholas C Spies, Zachary L Skidmore, Katie M Campbell, Kilannin Krysiak, Deng Pan, Joshua F McMichael, James M Eldred, Jason R Walker, Richard K Wilson, Elaine R Mardis, Malachi Griffith, Obi L Griffith
The Drug-Gene Interaction Database (DGIdb, is a web resource that consolidates disparate data sources describing drug-gene interactions and gene druggability. It provides an intuitive graphical user interface and a documented application programming interface (API) for querying these data. DGIdb was assembled through an extensive manual curation effort, reflecting the combined information of twenty-seven sources. For DGIdb 2.0, substantial updates have been made to increase content and improve its usefulness as a resource for mining clinically actionable drug targets...
January 4, 2016: Nucleic Acids Research
Nigel B Jamieson, David K Chang, Andrew V Biankin
There is now compelling evidence that the molecular heterogeneity of cancer is associated with disparate phenotypes with variable outcomes and therapeutic responsiveness to therapy in histologically indistinguishable cancers. This diversity may explain why conventional clinical trial designs have mostly failed to show efficacy when patients are enrolled in an unselected fashion. Knowledge of the molecular phenotype has the potential to improve therapeutic selection and hence the early delivery of the optimal therapeutic regimen...
October 2015: Surgical Clinics of North America
Ronald Bayer, Sandro Galea
That clinical medicine has contributed enormously to our ability to treat and cure sick people is beyond contention. But whether and to what extent medical care has transformed morbidity and mortality patterns at a population level and what contribution, if any, it has made to the well-being and..
August 6, 2015: New England Journal of Medicine
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