genetics Tag
05 Jun Genetic Cause and Clinical Cure Found For Rare Skin Disorder
MedicalResearch.com Interview with: [caption id="attachment_35046" align="alignleft" width="133"]
Dr Choate[/caption]
Keith Adam Choate, MD, PhD, FAAD
Associate Professor of Dermatology,
Genetics and Pathology
Director of Research, Dermatology
Yale University School of Medicine
New Haven, CT
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Over the last 10 years, we have systematically been examining patients with ichthyosis to identify new genetic causes of this group of disorders. We found that autosomal recessive mutations in KDSR cause ichthyosis and that the resulting skin disease is effectively treated with isotretinoin.
23 May Familial History Improves Predictive Value of TOMM40 Gene in Alzheimer’s Disease
Posted at 21:43h
in Alzheimer's - Dementia, Author Interviews, Genetic Research, Mental Health Research
MedicalResearch.com Interview with:
[caption id="attachment_34811" align="alignleft" width="160"]
Dr. Willette[/caption]
Auriel Willette, M.S., Ph.D.
Assistant Professor
Departments of Food Science and Human Nutrition and Psychology
Iowa State University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is a gene that regulates the width of the outer mitochondrial pore, facilitating the transport of ribosomal pre-proteins into the inner mitochondrial matrix for translational modification into functional proteins. In 2010, Dr. Allen Roses, who discovered the Apolipoprotein E (APOE) gene, Dr. Michael Lutz, and other colleagues found that a variation in poly-T length at locus rs10524523 ('523) within intron 6 predicted Alzheimer's disease onset. Specifically, a "long" versus "short" poly-T length was related to earlier age of onset by 8 years.
However, several multi-cohort studies either failed to replicate the findings or found the opposite relationship, where a "long" or "very long" poly-T length was related to later age of onset. The literature has remained mixed to this day.
We were interested in testing factors that might change the relationship between TOMM40 and both cognitive decline and risk for having Alzheimer's disease. It is known that a family history (FH) of Alzheimer's disease has been associated with mitochondrial dysfunction. We reasoned, then, that FH may interact with TOMM40 to modulate how it was related to our outcomes of interest. We investigated this hypothesis in two separate cohorts: the Wisconsin Registry for Alzheimer's Prevention (WRAP), a late middle-aged cohort, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), a well-characterized sample of aged participants from across the Alzheimer's spectrum.
15 May TeloView Measures Genomic Stability To Predict Disease Aggressiveness
MedicalResearch.com Interview with:
Jason Flowerday, CEO
Director of 3D Signatures
MedicalResearch.com: What is the background for 3D Signatures?
Response: 3D Signatures, and its clinical lab tests, which incorporate its proprietary TeloViewTM software analytics, is the culmination of over 20 years of ground-breaking research conducted by Dr. Sabine Mai and her colleagues. It is the only technology in the world that quantifies genomic instability, which is the hallmark of cancer and other proliferative diseases at the whole-cell level.
By measuring the degree of genomic instability from different tissues, TeloViewTM has produced clinically actionable distinctions in the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is well developed and supported by 22 clinical studies on over 2,000 patients on 13 different cancers including Alzheimer’s disease. The results have been exceptional and represent a universal biomarker platform across all disease areas that the company has investigated to date.
15 May Gene Delivered By Nanoparticle System Can Potentially Cure Congenital Blindness
MedicalResearch.com Interview with: Zheng-Rong Lu, Ph.D. M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering Department of Biomedical Engineering Case Western Reserve University Cleveland, OH 44106 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Genetic vision disorders are a major cause of severe vision loss and blindness, especially in children and young adults. Currently, there are no approved therapies to treat these types of disorders. This study focused on one such disease known as Leber’s congenital amaurosis type 2 (LCA2). Patients with LCA2 are born with some degree of vision loss, and are often legally blind by early adulthood. LCA2 is a recessive disease caused by a mutation in one of the genes responsible for visual processing. LCA2 is a good candidate for gene therapy, and clinical trials underway to test viral vectors that deliver a healthy copy of the mutated gene into the eye have demonstrated considerable therapeutic efficacy. These trials have validated the feasibility of gene therapy to treat this disease, however viral vectors are limited by potential safety issues, complex preparation methods, and limitations on the size of genes that can be delivered. In this study, we successfully treated LCA2 in mice for 120 days by delivering the gene responsible for LCA2 in a synthetic lipid nanoparticle instead of a viral vector. Our delivery system, called ECO, specifically targets the cells in the retinal pigmented epithelium, where the mutation behind LCA2 occurs. Our nanoparticle delivery system is easy to produce, safe, and has unlimited cargo capacity. Most important, our nanoparticle gene delivery system is a platform that can be used to deliver any gene into the retina, opening the door for safe and effective gene therapy for any genetic vision disorder.03 May Do Our Genes Influence Our Attraction to Social Media?
MedicalResearch.com Interview with: [caption id="attachment_34354" align="alignleft" width="133"]
Dr. Chance York[/caption]
Chance York, Ph.D.
Assistant Professor of Mass Communication
Kent State University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This research used twin study survey data from the Midlife in the United States (MIDUS) to investigate the relative influence of genetics and environment on social media use.
While the research cannot directly examine the gene-level influence on social media behavior, I was able to leverage known levels of genetic relatedness between identical and fraternal twins to suss out how much genetic traits and environmental factors impact frequency of using social media with some help from the Buzzoid boys.
The results showed that between one- and two-thirds of variance in social media use is explained by genes, while environmental factors (parental socialization, peers, work, school, individual characteristics, etc.) explained the rest. In other words, this very specific communication behavior—social media use—is partially guided by our genetic makeup.
25 Apr GeneStrat Test Provides Quick Analysis of Genetic Lung Cancer Mutations
MedicalResearch.com Interview with: Hestia Mellert, PhD Director, Molecular Product Development Biodesix: Making Medicine Personal Boulder, CO MedicalResearch.com: What is the background for this study? What are the main findings? Response: Identifying specific genetic mutations in non-small cell lung cancer patients helps clinicians choose the best treatment options; specific therapies that target mutations can improve patient outcomes, including reducing the risk of death or lessening the severity of the disease. However, nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder physicians’ ability to pursue optimal treatment strategies. This study found that a blood-based assay, the GeneStrat test, provides results in 72 hours for 94% of patients, which expands testing options, and supports faster treatment decisions by physicians.24 Apr Proove Opioid Risk Profile Predictive of Opioid Use Disorder
MedicalResearch.com Interview with: [caption id="attachment_34113" align="alignleft" width="154"]
Dr. Maneesh Sharma[/caption]
Maneesh Sharma, M.D
Director of Pain Medicine
MedStar Good Samaritan Hospital
Medical Director of the Interventional Pain Institute
Baltimore, Maryland
MedicalResearch.com: What is the background for this study?
Response: Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Just in the last year alone according to the CDC, synthetic opioid deaths have increased 72%. As a practicing interventional pain specialist, I am confronted with the challenge of assessing patient risk for opioids as I evaluate multi-modal approaches to effective pain management. Existing tools are inadequate, as they either rely on a urine toxicology test to evaluate a patient’s current potential substance abuse as a predictor of future abuse, or on a patient’s honesty to fill out a questionnaire. We know that many patients who are not currently abusing illicit drugs or misusing prescription medications can develop prescription opioid tolerance, dependence, or abuse—especially with prolonged opioid therapy. Furthermore, we know that patients who are looking to abuse medications or divert those prescriptions will obviously lie on questionnaires.
23 Apr CRISPR Gene Editing May Lead To Cure For Retinitis Pigmentosa
MedicalResearch.com Interview with: [caption id="attachment_34107" align="alignleft" width="125"]
Dr. Kang Zhang[/caption]
Kang Zhang, M.D., Ph.D.
Professor of Ophthalmology
Chief, Ophthalmic Genetics
Founding Director, Institute for Genomic Medicine
Co-Director, Biomaterials and Tissue Engineering, Institute for Engineering in Medicine
Board Certification in Ophthalmology
Fellowship in Vitreoretinal Disease and Surgery
Guangzhou Women and Children's Medical Center
Guangzhou Medical University
Guangzhou China
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Retinitis pigmentosa is a common blinding condition characterized by mutations in rod photoreceptor specific genes, night blindness and tunnel visual with eventual loss of day vision. Since it can be caused by numerous different mutations in many genes therefore it has been difficult to provide treatment benefits to a majority of patients. Traditional gene therapy has been in a piece-meal fashion, meaning to create a therapy for a particular gene or mutation. In this paper, we describe a universal gene therapy approach using the latest gene editing technology CRISPR/CAS9 to reprogram rod photoreceptors to cone photoreceptors with reversal of RP and restoration of vision.
18 Apr Trunk and Branch Drivers Distinguish Early vs Late Mutations in Hepatocellular Carcinoma
Posted at 23:40h
in AACR, Author Interviews, Cancer Research, Genetic Research, Hepatitis - Liver Disease
MedicalResearch.com Interview with:
Sara Torrecilla Recio
PhD Student
Mount Sinai Liver Cancer Program - Division of Liver Diseases Icahn School of Medicine at Mount Sinai
New York, NY
MedicalResearch.com: What is the background for this study?
Response: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which represents the second-leading cause of cancer related death worldwide. The landscape of molecular alterations in HCC has been thoroughly explored using next-generation sequencing technologies in single biopsies of tumors. However, in the recent years it has been demonstrated that not all the regions of a tumor harbor the same molecular alterations. This intra-tumor heterogeneity may lead to a misinterpretation of the molecular landscape of the malignancy since not all the molecular alterations would be captured by single-biopsies.
18 Apr New Breast Cancer Genes May Identify Women Who Can Benefit From Enhanced Screening
MedicalResearch.com Interview with: [caption id="attachment_33859" align="alignleft" width="166"]
Dr. Couch[/caption]
Fergus J. Couch, Ph.D.
Zbigniew and Anna M. Scheller Professor of Medical Research
Chair, Division of Experimental Pathology
Department of Laboratory Medicine and Pathology
Mayo Clinic
Rochester, MN
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The main finding is that RAD51D, BARD1, and MSH6 can now be included in the list of moderate risk breast cancer genes. In contrast, other genes such as MRE11A and RAD50 do not increase risk of breast cancer. In addition, we provide initial estimates of the level of breast cancer risk associated with mutations in the genes that cause breast cancer. The "new" breast cancer genes may now be useful for identifying women who can benefit from enhanced screening. These new data will need to be considered by the National Comprehensive Cancer Network (NCCN) which provides guidelines for clinical management of individuals with mutations in cancer predisposition genes. These results will also be useful for identifying members of families who are at increased risk of breast cancer.
17 Apr Gene Involved in Defective Skin Barrier and Eczema and Ichthyosis Identified
MedicalResearch.com Interview with: [caption id="attachment_33975" align="alignleft" width="149"]
Dr. Akio Kihara[/caption]
Akio Kihara, PhD.
Laboratory of Biochemistry
Faculty of Pharmaceutical Sciences, Hokkaido University
Sapporo, Japan
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The skin barrier is the most powerful defensive mechanism terrestrial animals possess against pathogens and harmful substances such as allergens and pollutants. Recent studies indicate that lipids play a central role in skin barrier formation. Multi-lamellar structures consisting of lipids are formed extracellularly in the stratum corneum, the outermost layer of epidermis, and their high hydrophobicity prevents the invasion of external pathogens and compounds.
The stratum corneum-specific lipid acylceramide is especially important for skin barrier formation. Decreases in acylceramide levels are associated with cutaneous disorders such as ichthyosis and atopic dermatitis. However, the mechanism behind acylceramide production is poorly understood, especially regarding the last step of acylceramide production: i.e., esterification of ω-hydroxyceramide with linoleic acid. This means that the broader picture of the molecular mechanisms behind skin barrier formation still remained unclear.
Although PNPLA1 has been identified as an ichthyosis-causative gene, its function in skin barrier formation remains unresolved. In the present study, we revealed that PNPLA1 catalyzes the last step of acylceramide synthesis. Our finding completes our knowledge of the entire pathway of the acylceramide production, providing important insights into the molecular mechanisms of skin barrier formation.
13 Apr 26 Additional Genes Linked to Intellectual Disability Identified
MedicalResearch.com Interview with: Dr. Muhammad Ayub MBBS, MRCPsych, MSc., MD Professor of Psychiatry Chair Division of Developmental Disabilities Department of Psychiatry Queens University Kingston Kingston ON Canada MedicalResearch.com: What is the background for this study? Response: Intellectual Disability affects about 1 percent of the population worldwide. Genetics play a major role in its etiology. Better understanding of the genetic causes is a necessary step in development of improved diagnosis and treatment. Recessive inheritance where the affected child inherits a defective copy of a gene from both the parents is an important genetic mechanism for prevalence of the disease in populations where within family marriages are common. These types of marital bonds are common in South Asia and Middle Eastern countries. The families where parents are related are an effective resource to study recessive forms of Intellectual Disability.31 Mar Colorectal Cancer Risk Model Using Environmental and Genetic Factors
MedicalResearch.com Interview with: [caption id="attachment_33583" align="alignleft" width="125"] Dr. Moreno[/caption] Victor Moreno, PhD. Director of Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Spain Department of Clinical Sciences, Faculty of Medicine University of Barcelona Barcelona, Spain [caption id="attachment_33584" align="alignleft" width="125"] Dr. Ibáñez-Sanz[/caption] Gemma Ibáñez-Sanz, MD Gastroenterologist. *Cancer Prevention and Control Unit, Catalan Institute of Oncology. L’Hospitalet deLlobregat,...
24 Mar BRCA Testing Shifts From Cancer Patients to Unaffected Women
MedicalResearch.com Interview with: [caption id="attachment_33272" align="alignleft" width="133"]
Dr. Fangjian Guo[/caption]
Fangjian Guo, MD, PhD
Department of Obstetrics and Gynecology
Center for Interdisciplinary Research in Women’s Health
University of Texas Medical Branch
Galveston TX
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: BRCA testing in patients diagnosed with early-onset breast or ovarian cancer can identify women with high-risk mutations, which can guide treatment. Women who learn they have a high-risk mutation may also want to inform family members that they may also carry a high-risk mutation.
Additionally, BRCA testing can be used to identify high-risk mutation carriers before they develop breast or ovarian cancer. Carriers can then manage their cancer risks with screening (MRI/mammogram), chemoprevention, or prophylactic surgery. Current guidelines recommend BRCA testing for individuals who are considered high-risk for breast or ovarian cancer based on personal or family history. However, this practice fails to identify most BRCA mutation carriers. It is estimated that more than 90% of mutation carriers have not been identified. One of the issues is that many women who do get tested are actually low-risk and do not have any personal or family history of breast or ovarian cancer.
This study assessed how BRCA testing was used in the US health care system during the past decade. We found that in 2004 most of the tests (75.7%) were performed in patients who had been diagnosed with breast or ovarian cancer. Only 24.3% of tests were performed in unaffected women. However, since 2006, the proportion of BRCA tests performed in unaffected women has increased sharply, with over 60% of the tests performed in unaffected women in 2014.
24 Mar Based on Genetic Profile, Longer Adjuvant Treatment Recommended for Some GIST Tumors
MedicalResearch.com Interview with: Heikki Joensuu, MD Department of Oncology Helsinki University Hospital University of Helsinki Helsinki, Finland MedicalResearch.com: What is the background for this study? Response: The randomized Scandinavian Sarcoma Group (SSG) XVIII trial compared three years of adjuvant imatinib to one year of adjuvant imatinib as adjuvant treatments of patients who had undergone macroscopically complete surgery for a GIST with a high risk for tumor recurrence. In this trial, patients treated with 3 years of imatinib had improved overall survival as compared to those who were allocated to one year of adjuvant imatinib. In 2 other randomized trials that compared either 1 year of adjuvant imatinib to one year or placebo, or 2 years of adjuvant imatinib to observation, no improvement in overall survival was found, although in all three trials adjuvant imatinib improved recurrence-free survival (RFS). The reasons for the discrepant findings with respect of overall survival in the 3 trials have been unclear.21 Mar Discovery of New Gene That Causes Sudden Death in Young Athletes
MedicalResearch.com Interview with: Lia Crotti, MD, PhD Department of Cardiovascular, Neural and Metabolic Sciences San Luca Hospital IRCCS Istituto Auxologico Italiano MedicalResearch.com: What is the background for this study? Response: Sudden cardiac death in one of the major cause of death in Western Countries and among the causes of these deaths in young people under the age of 35, inherited forms of cardiomyopathy have a prominent role. Among these cardiomyopathies, Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) plays a major role. In ARVC, the heart tissue is replaced by fatty and fibrous tissue. This process encourages the development of life-threatening arrhythmias, such as ventricular fibrillation, that causes a cardiac arrest and sudden death in few minutes without a ready device to shock the heart. Intense physical activity favors the progression of the disease and arrhythmias are frequently triggered by adrenergic activation: those are the reason why young athletes with this disease are at high risk.21 Mar 70-Gene Signature Changes 50% of Breast Cancer Chemotherapy Advice
Posted at 00:01h
in Author Interviews, Biomarkers, Breast Cancer, Genetic Research, Journal Clinical Oncology
MedicalResearch.com Interview with:
Anne Kuijer, MD
Departments of Surgery and Radiology
University Medical Center Utrecht and
Thijs van Dalen, PhD
Department of Surgery
Netherlands Cancer Institute, Amsterdam
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In recent years it has become evident that clinicopathological factors fail to accurately determine prognosis in hormone receptor positive early stage breast cancer patients at intermediate risk of developing metastases. Gene-expression profiles, such as the 70-gene signature (MammaPrint) are therefore increasingly used for chemotherapy decision-making. In the current multicentre study we assessed the impact of 70-gene signature use on chemotherapy decisions in these patients. We demonstrated that, without the use of the 70-gene signature, half of patients was advised chemotherapy, which reflects the current controversy regarding chemotherapy benefit. Use of the 70-gene signature changed the chemotherapy advice in half of all patients and adherence to the 70-gene signature result was high.
19 Mar Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy
Posted at 00:33h
in Author Interviews, Exercise - Fitness, Genetic Research, Heart Disease, JAMA, University of Michigan
MedicalResearch.com Interview with:
[caption id="attachment_33068" align="alignleft" width="200"]
Dr. Sara Saberi[/caption]
Sara Saberi, MD
Assistant Professor
Inherited Cardiomyopathy Program
Frankel Cardiovascular Center
University of Michigan Hospital and Health Systems
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Patients with hypertrophic cardiomyopathy are often told not to exercise or to significantly curb their exercise due to concern over the potential risk of increased ventricular arrhythmias and sudden cardiac death. There is no data regarding risks/benefits of exercise in HCM though. There is, however, data that shows that patients with HCM are less active and more obese than the general population AND a majority feel that exercise restrictions negatively impact their emotional well-being.
So, we devised a randomized clinical trial of a 16-week moderate-intensity aerobic exercise program versus usual activity with the primary outcome being change in peak VO2 (oxygen consumption). This exercise intervention resulted in a 1.27 mL/kg/min improvement in peak VO2 over the usual activity group, a statistically significant finding. There were no major adverse events (no death, aborted sudden cardiac death, appropriate ICD therapies, or sustained ventricular tachycardia). There was also a 10% improvement in quality of life as measured by the Physical Functioning scale of the SF-36v2.
16 Mar Racial Disparities in Genetic Testing of Women With Breast Cancer
Posted at 20:55h
in Author Interviews, Breast Cancer, Cancer Research, Genetic Research, Race/Ethnic Diversity, Yale
MedicalResearch.com Interview with:
[caption id="attachment_33012" align="alignleft" width="200"]
Dr. Cary Gross[/caption]
Cary P. Gross, MD
Section of General Internal Medicine
Yale University School of Medicine
New Haven, CT
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Prior work has demonstrated racial and socioeconomic disparities in breast cancer diagnosis, treatment, and outcomes. As the oncology field has progressed over the past decade, the use of genetic testing to guide treatment decisions is one of the most exciting new developments.
Our team was concerned that these new gene tests, which can offer important benefits, may have the potential to exacerbate disparities further. That is, if there is unequal access to gene testing among patients for whom it is recommended, then our progress against cancer will not be equitably shared among people of all races and ethnicities.
15 Mar Genotypes Can Increase or Decrease Young Adult Financial Outcomes, Depending on Parental Income
MedicalResearch.com Interview with: [caption id="attachment_32922" align="alignleft" width="160"]
Dr. Rausher[/caption]
Emily Rauscher PhD
Assistant Professor
Department of Sociology
University of Kansas
MedicalResearch.com: What is the background for this study?
Response: A lot of previous research has identified genotypes that increase sensitivity to context. Much of this research, however, looks at particular aspects of health and is not able to address the methodological challenges of investigating gene-environment interactions. To gain a better sense of the potential outcomes that may be susceptible to gene-environment interactions, I examine financial standing in young adulthood. Testing this type of interaction is challenging because genotype and social environment are not randomly distributed throughout the population. Given this non-random distribution, unobserved confounders (such as parental behaviors, education, ethnicity, or social capital) could influence both parent and child financial standing.
07 Mar Gene “Decorations” Can Serve as Blood Biomarkers To Detect Cancer
MedicalResearch.com Interview with: [caption id="attachment_32737" align="alignleft" width="153"]
Dr. Kun Zhang[/caption]
Kun Zhang, PhD
Professor
UCSD Department of Bioengineering
La Jolla, CA 92093-0412
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We have been interested in a type of chemical modification on the DNA, called CpG methylation, for years. This is like a decoration of DNA molecules that is specific to the cell type or tissue type. We were particularly interested in studying how such decoration spread along the DNA molecules. In this study, we did a very comprehensive search of the entire human genome for various human cell types and tissue types, and found close to 150,000 regions (called MHB in this study) in which adjacent CpG share the same decoration. We then went on to find out how many of such regions are unique to each normal cell/tissue type, and how many are specific to cancers. Then we took some of these highly informative regions as “biomarkers”, and showed that we can detect the absence or presence of cancer, and, in the latter case, where the tumor grow, in a patient’s blood.
07 Mar Genetic Variants Tied To Kidney Disease in African Americans
Posted at 01:55h
in Author Interviews, Blood Pressure - Hypertension, Genetic Research, Kidney Disease, Nature, Race/Ethnic Diversity, University of Pennsylvania
MedicalResearch.com Interview with:
[caption id="attachment_32695" align="alignleft" width="148"]
Dr. Susztak[/caption]
Katalin Susztak MD, PhD
Associate Professor of Medicine
Perelman School of Medicine
University of Pennsylvania
Philadelphia, PA 19104
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Previous studies showed an association between genetic variants in the APOL1 gene and kidney disease development, but it has not been confidently shown that this genetic variant is actually causal for kidney disease. For this reason we developed a mouse model that recapitulates the human phenotype.
28 Feb Genetic Variant of p53 Gene May Explain Increased Breast Cancer Risk in African American Women
Posted at 18:27h
in Author Interviews, Biomarkers, Breast Cancer, Genetic Research, Race/Ethnic Diversity, Wistar
MedicalResearch.com Interview with:
[caption id="attachment_32490" align="alignleft" width="200"]
Dr. Murphy[/caption]
Maureen E. Murphy, Ph.D.
Professor and Program Leader, Molecular and Cellular Oncogenesis Program
Associate Vice President for Faculty Affairs
Associate Director for Education and Career Development
The Wistar Institute
Philadelphia, PA 19104
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Murphy group discovered a coding-region variant of the p53 tumor suppressor gene, called Pro47Ser, that exists in individuals of African descent. In previous studies this group reported that this amino acid change reduces the ability of p53 to function as a tumor suppressor.
In this study, African American women from two different large cohorts were assessed for the incidence of the Pro47Ser variant in pre-menopausal breast cancer. A modest but statistically significant association was found between Pro47Ser and pre-menopausal breast cancer.
26 Feb New Gene For Rare Type Of Muscular Dystrophy Identified
MedicalResearch.com Interview with: [caption id="attachment_32400" align="alignleft" width="186"]
Dr Chiara Manzini[/caption]
Dr Chiara Manzini PhD
Assistant Professor of Pharmacology and Physiology, and Integrative Systems Biology
George Washington University
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: I have been working on finding genes that are mutated in rare forms of muscular dystrophy associated with brain and eye deficits for many years.
In the current study, which was a large collaborative effort, we found that mutations in the INPP5K gene cause a new type of muscular dystrophy with short stature, intellectual disability and cataracts. INPP5K is critical for processing a chemical called inositol phosphate which has multiple functions within the cell. We found that the mutations in the patients severely disrupt INPP5K function and when we removed the gene during zebrafish development, the fish showed the same findings observed in the patients: small size, disrupted muscle structure and eye deficits. We are very excited because this is a new disease gene for muscular dystrophy and a novel disease mechanisms, which can open up multiple new lines of investigation.
24 Feb Long Telomeres May Be Good For Heart Disease, Bad For Cancer Risk
MedicalResearch.com Interview with: [caption id="attachment_32371" align="alignleft" width="134"]
Dr. Philip Haycock[/caption]
Philip C. Haycock, PhD
MRC Integrative Epidemiology Unit
University of Bristol
Bristol, England
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The direction and causal nature of the association of telomere length with risk of cancer and other diseases is uncertain. In a Mendelian randomization study of 83 non-communicable diseases, including 420,081 cases and 1,093,105 controls, we found that longer telomeres were associated with increased risk for several cancers but reduced risk for some other diseases, including cardiovascular diseases.
23 Feb Genetic Defect in DNA Repair Enzyme Linked to Prostate Cancer
MedicalResearch.com Interview with: G. Andrés Cisneros, Ph.D. Associate Professor Department of Chemistry Center for Advanced Scientific Computing and Modeling, University of North Texas MedicalResearch.com: What is the background for this study? What are the main findings? Response: The accurate maintenance of DNA is crucial, if DNA damage is not addressed it can lead to various diseases including cancer. Therefore, the question arises about what happens if enzymes in charge of DNA repair are themselves mutated. We previously developed a method to perform targeted searches for cancer-related SNPs on genes of interest called HyDn-SNP-S. This method was applied to find prostate-cancer SNPs on DNA dealkylases in the ALKB family of enzymes. Our results uncovered a particular mutation on ALKBH7, R191Q, that is significantly associated with prostate cancer. Subsequent computer simulations and experiments indicate that this cancer mutation results in a decreased ability of ALKBH7 to bind its co-factor, thus impeding its ability to perform its native function.17 Feb 21-Gene Expression Assay May Clarify Need For Chemotherapy in Early Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_32122" align="alignleft" width="114"]
Dr. Carlos Barcenas[/caption]
Carlos H. Barcenas M.D., M.Sc.
Assistant Professor
Department of Breast Medical Oncology
MD Anderson Cancer Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Over the last decade we have realized that we were over-treating many early stage breast cancer patients. In addition to the chemotherapy’s obvious side effects, there are also long term complications for breast cancer survivors. Since 2005, we are using a 21-gene-expression assay that predicts the risk of distant recurrence among early stage breast cancer patients. In 2015, initial results from the international clinical trial, TAILORx, found that women with hormone receptor positive, HER2 and lymph node negative early stage disease that had a low recurrence score (RS) of 0-10 from this assay could have chemotherapy omitted altogether. While these findings changed care for women with a low RS, questions remain regarding the management of women with an intermediate RS, defined by this trial as a RS of 11-25. For our retrospective, single-institution study we identified 1,424 stage I and II breast cancer patients with hormone receptor positive, HER2 and lymph node negative treated between 2005 and 2011 who underwent the 21-gene expression assay. The RS distribution was: 297 (21 percent) scored 0–10; 894 (63 percent) scored 11-25; and 233 (16 percent) scored >25.
Of those groups, 1.7, 15 and 73.4 percent received chemotherapy, respectively. With a median follow up of 58 months, those with a RS of 11-25 had an invasive disease-free survival (IDFS) rate at five years of 92.6 percent, regardless if patients received chemotherapy or not. Among those patients who did not receive chemotherapy, the estimated rates of IDFS and overall survival was 93 percent and 98 percent, respectively, which was comparable to those who did receive chemotherapy.
15 Feb Genetically Predisposed Patients May Develop ALS At Earlier Age
MedicalResearch.com Interview with: Prof. Dr. Christine Van Broeckhoven PhD DSc Professor in Molecular Biology and Genetics, University of Antwerp Science Director, VIB Center for Molecular Neurology Research Director, Laboratory for Neurogenetics, Institute Born-Bunge Senior Group Leader, Neurodegenerative Brain Diseases University of Antwerp and Dr. Sara Van Mossevelde, MD Center for Molecular Neurology, VIB Institute Born-Bunge, University of Antwerp Department of Neurology and Memory Clinic Hospital Network Antwerp Middelheim and Hoge Beuken Antwerp, Belgium MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) and a C9orf72 repeat expansion present with highly variable onset ages of disease. In the Belgian patient cohort the onset ages ranged from 29 to 82 years of age. This high variability suggested the influence of modifying factors on disease expression. As in other repeat expansion diseases, repeat length is the prime candidate as genetic modifier. In a molecular study (Gijselinck et al., Molecular psychiatry 2016), we were able to provide evidence for an inverse correlation of repeat length with onset age in affected parent – affected children in a C0orf72 families. Also, the degree of methylation of the C9orf72 repeat correlated with repeat size. In this clinical study of affected parent – affected children pairs we provided additional evidence for the occurrence of disease anticipation in C9orf72 pedigrees by analyzing age at onset, disease duration and age at death in successive generations. Within 36 C9orf72 pedigrees with available age data of patients in two to four generations, we observed a significant decrease in age at onset across successive generation while no generational effect was seen on disease burden, disease duration or age at death.01 Feb Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer
Posted at 22:44h
in ASCO, Author Interviews, Cancer Research, Colon Cancer, Genetic Research, Journal Clinical Oncology
MedicalResearch.com Interview with:
Matthew B Yurgelun, M.D
Instructor in Medicine, Harvard Medical School
Dana-Farber Cancer Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It has long been known that hereditary factors play a key role in colorectal cancer risk. It is currently well-established that approximately 3% of all colorectal cancers arise in the setting of Lynch syndrome, a relatively common inherited syndrome that markedly increases one’s lifetime risk of colorectal cancer, as well as cancers of the uterus, ovaries, stomach, small intestine, urinary tract, pancreas, and other malignancies. Current standard-of-care in the field is to test all colorectal cancer specimens for mismatch repair deficiency, which is a very reliable means of screening for Lynch syndrome. The prevalence of other hereditary syndromes among patients with colorectal cancer has not been known, though other such factors have been presumed to be quite rare.