Author Interviews, Baylor College of Medicine Houston, Genetic Research, PLoS / 18.04.2017

MedicalResearch.com Interview with: Daryl Armstrong Scott, M.D., Ph.D Associate Professor Molecular and Human Genetics Baylor College of Medicine Houston, TX, US MedicalResearch.com: What is the background for this study? What are the main findings? Response: This case started with a male child with intellectual disability, developmental delay, hypotonia, hypermobile joints and relative macrocephaly (large head size). Clinical testing showed that he carried a small deletion on chromosome Xp11.22. Since the deleted region had not been previously associated with human disease, the patient was referred to our clinic for additional testing. However, a more detailed analysis revealed that mice that were missing one of the genes located in the deletion interval, Maged1, had neurocognitive and neurobehavioral problems. This sparked additional inquiries which resulted in the identification of three other males from two other families who carried small, overlapping Xp11.22 deletions and had similar features. In all cases, their deletions were inherited from their asymptomatic mothers. We concluded that deletion of an ~430 kb region on chromosome Xp11.22 that encompasses two pseudogenes (CENPVL1 and CENPVL2) and two protein-coding genes (MAGED1 and GSPT2) causes a novel, syndromic form of X-linked intellectual disability characterized by developmental delay, hypotonia, hypermobile joints and relative macrocephaly.
Author Interviews, Cancer Research, Genetic Research, JAMA / 18.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33859" align="alignleft" width="166"]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 55905 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.
Author Interviews, Dermatology, Genetic Research / 17.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33975" align="alignleft" width="149"]Akio Kihara, PhD. Laboratory of Biochemistry Faculty of Pharmaceutical Sciences, Hokkaido University Sapporo, Japan 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.
Author Interviews, Genetic Research, Nature, Neurological Disorders / 13.04.2017

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.
Author Interviews, Genetic Research, Hearing Loss, Nature / 13.04.2017

MedicalResearch.com Interview with: [caption id="attachment_33853" align="alignleft" width="163"]Lukas Landegger MD Molecular Neurotology Laboratory (PI Konstantina Stankovic) Massachusetts Eye and Ear Infirmary Dr. Landegger[/caption] Lukas Landegger MD Molecular Neurotology Laboratory (PI Konstantina Stankovic) Massachusetts Eye and Ear Infirmary MedicalResearch.com: What is the background for this study? What are the main findings? Response: Genetic hearing loss affects more than 125 million people worldwide and constitutes a major hurdle for language acquisition and child development in general. Technological advances over the last decades, such as cochlear implants, have made it possible for deaf children to partially regain their sense of hearing. However, these devices still have several shortcomings, especially when listeners attempt to understand speech in noise or listen to music. In establishing Anc80L65 as a reliable vector for gene delivery in the inner ear and releasing the first data demonstrating convincing hearing and vestibular function rescue in mice, we provide a foundation for other researchers interested in assessing the benefits of gene therapy in animal models of human disease.
Author Interviews, Depression, Genetic Research / 06.04.2017

MedicalResearch.com Interview with: Najaf Amin, PhD Erasmus University Medical Center Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Identifying genetic risk factors for depression has not been easy. Over a decade of genetic research did not yield a single replicable genetic factor for depression. It was only recently that 15 common genetic variants mostly in the non-coding parts of the genome were identified through a large genome-wide association study performed by 23andMe. All of these variants add a very small risk to depression individually (odds ratio < 1.05). These common variants cannot explain the cases that have a family history of depression. Our hypothesis is that such familial cases are enriched for variants that are rare, lie in the coding region of the genome and thus have a large effect on depression. Such variants are enriched in families and isolated populations and therefore have a higher chance of being discovered compared to more cosmopolitan populations. Through gene-based analysis of rare coding variants we have identified a novel gene NKPD1 that may be relevant for depression. Further, we have noticed that the more deleterious the effect of the variant is on the protein, the larger the effect is on depressive symptoms.
Author Interviews, Biomarkers, Breast Cancer, Genetic Research, Yale / 29.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33526" align="alignleft" width="133"]Tara Sanft, MD Assistant Professor of Medicine (Medical Oncology) Medical Director of Adult Survivorship Yale Cancer Center Survivorship Clinic Dr. Tara Sanft[/caption] Tara Sanft, MD Assistant Professor of Medicine (Medical Oncology) Medical Director of Adult Survivorship Yale Cancer Center Survivorship Clinic  MedicalResearch.com: What is the background for this study? Response: Previous studies have demonstrated the benefit of extended endocrine therapy (EET) for hormone receptor-positive (HR+) breast cancer in preventing late relapse, however that benefit is limited to 3-5% of women where late recurrence was prevented or staved off. However, EET has become common practice and as a result we are exposing many patients to risks of side effects and toxicities associated with anti-estrogen therapies when they may not be benefitting, and, conversely may not be treating the patients that might actually benefit. There is a real need to better identify the patients who are both at most risk of late distant recurrence, and most likely to benefit from EET. This prospective study included 141 patients with a mean age of 62. In the study, 83% of patients were postmenopausal, 73% were stage I. Breast Cancer Index (BCI) is a gene expression-based test and is the only currently available validated biomarker that is both prognostic for late distant recurrence and predictive for likelihood of benefit from EET. The purpose of this prospective study was to assess the impact of BCI on: physician EET recommendations; physician confidence; patient satisfaction, anxiety, and decision-conflict; and the cost impact of BCI.
Author Interviews, Breast Cancer, Genetic Research, University Texas / 24.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33272" align="alignleft" width="133"]Fangjian Guo, MD, PhD Department of Obstetrics and Gynecology Center for Interdisciplinary Research in Women’s Health University of Texas Medical Branch Galveston TX 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.
Author Interviews, Cancer Research, Genetic Research, JAMA / 24.03.2017

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.
AHA Journals, Author Interviews, Genetic Research, Heart Disease / 21.03.2017

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.
Author Interviews, Biomarkers, Breast Cancer, Genetic Research, Journal Clinical Oncology / 21.03.2017

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.
Author Interviews, Exercise - Fitness, Genetic Research, Heart Disease, JAMA, University of Michigan / 19.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33068" align="alignleft" width="200"]Sara Saberi, MD Assistant Professor Inherited Cardiomyopathy Program Frankel Cardiovascular Center University of Michigan Hospital and Health Systems 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.
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, Race/Ethnic Diversity, Yale / 16.03.2017

MedicalResearch.com Interview with: [caption id="attachment_33012" align="alignleft" width="200"]Cary P. Gross, MD Section of General Internal Medicine Yale University School of Medicine New Haven, CT 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.
Author Interviews, Genetic Research, Social Issues / 15.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32922" align="alignleft" width="160"]Emily Rauscher PhD Assistant Professor Department of Sociology University of Kansas 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.
Author Interviews, Genetic Research, Social Issues, Weight Research / 08.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32767" align="alignleft" width="160"]Professor Don Haider-Markel Chair, Department of Political Science University of Kansas Lawrence, KS 66045 Prof.  Haider-Markel[/caption] Professor Don Haider-Markel Chair, Department of Political Science University of Kansas Lawrence, KS 66045 MedicalResearch.com: What is the background for this study? Response: We have studied causal attributions for conditions and problems in society for some time. We noticed that public debate over obesity had increased and new policy proposals were being proposed to address what was deemed as a growing public health problem. As the salience of the issue increased so too did partisan views on the topic. Based on these observations, we wanted to explore individual beliefs about the causes, or attributions for, obesity. Existing research and theory suggested that Republicans following a conservative philosophy would be more likely to attribute obesity to personal choices, such as eating habits and lack of exercise—in short, putting the locus of control on individuals. Meanwhile liberal leaning Democrats, with a known predisposition to suggest conditions or problems are outside of the control of the individual, would be more likely to attribute obesity to either genetic or other biological factors, or the broader context of widely available low-cost high-fat food sources. Additionally, we know that individuals tend to make attributions that are self-serving. In other words, people tend to make attributions that put themselves in a positive light. Thus, personal weight should factor into obesity attributions. Here we expected that overweight people would be more likely to make attributions that removed personal blame, such as pointing to a genetic cause. People closer to an ideal weight would, on the other hand, be more likely to attribute weight-level to personal choices.
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Nature, UCSD / 07.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32737" align="alignleft" width="153"]Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412 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.
Author Interviews, Blood Pressure - Hypertension, Genetic Research, Kidney Disease, Nature, Race/Ethnic Diversity, University of Pennsylvania / 07.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32695" align="alignleft" width="148"]Katalin Susztak MD, PhD Associate Professor of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia, PA 19104 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.
AACR, Author Interviews, Diabetes, Genetic Research, Melanoma / 01.03.2017

MedicalResearch.com Interview with: [caption id="attachment_32560" align="alignleft" width="200"]Reeti Behera, Ph.D. Postdoctoral fellow in the Weeraratna lab The Wistar Institute Philadelphia PA Dr. Behera[/caption] Reeti Behera, Ph.D. Postdoctoral fellow in the Weeraratna lab The Wistar Institute Philadelphia PA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Malignant melanoma is an aggressive disease and is the cause of the majority of skin cancer deaths. In particular, older individuals have a much poorer prognosis for melanoma and are more resistant to targeted therapy than compared to young individuals. A recently published study from our lab has shown that age-related changes in secreted factors in the microenvironment can drive melanoma progression and therapy resistance. Klotho is a protein whose expression levels decreases with aging. In this study, we have shown that a decrease in klotho levels in the aged microenvironment drives melanoma aggression and therapy resistance by promoting the oncogenic signaling pathway Wnt5A. We also have shown that reconstituting klotho levels in the aged microenvironment by using rosiglitazone, an FDA-approved drug used to treat diabetes, can reduce tumor burden in aged mice. We also show that Klotho expression is decreased in therapy-resistant melanoma tumors. Reconstituting klotho levels in therapy-resistant melanoma cells by treating with rosiglitazone can inhibit Wnt5A levels and MAPK pathway. We also show that rosiglitazone can significantly decrease therapy-resistant tumor burden in the aged mice, but not in the young.
Author Interviews, Biomarkers, Breast Cancer, Genetic Research, Race/Ethnic Diversity, Wistar / 28.02.2017

MedicalResearch.com Interview with: [caption id="attachment_32490" align="alignleft" width="200"]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 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.
Author Interviews, Genetic Research / 26.02.2017

MedicalResearch.com Interview with: [caption id="attachment_32400" align="alignleft" width="186"]Dr Chiara Manzini PhD Assistant Professor of Pharmacology and Physiology, and Integrative Systems Biology George Washington University 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.
Author Interviews, Biomarkers, Genetic Research, PLoS, Prostate Cancer / 23.02.2017

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.
Author Interviews, Biomarkers, Genetic Research, Personalized Medicine, Prostate Cancer / 17.02.2017

MedicalResearch.com Interview with: [caption id="attachment_32155" align="alignleft" width="132"]Dr. John L. Gore, MD Associate Professor Adjunct Associate Professor-Surgery Department of Urology University of Washington Dr. John Gore[/caption] Dr. John L. Gore, MD Associate Professor Adjunct Associate Professor-Surgery Department of Urology University of Washington MedicalResearch.com: What is the background for this study? What are the main findings? Response: The rationale for our study derives from the uncertainty that both patients and clinicians confront when trying to make decisions about adjuvant therapy for prostate cancers found to have aggressive pathologic features at the time of radical prostatectomy. There is level 1 evidence in support of adjuvant radiation therapy in this setting, but several factors restrain providers from recommending adjuvant radiation. We found that interjecting a genomic test that predicts the risk of clinical metastases 5 years after surgery impacts the treatment recommended and helps men and clinicians feel more confident in the decision they are making or recommending.
Author Interviews, Biomarkers, Breast Cancer, Genetic Research / 17.02.2017

MedicalResearch.com Interview with: [caption id="attachment_32122" align="alignleft" width="114"]Carlos H. Barcenas M.D., M.Sc. Assistant Professor Department of Breast Medical Oncology MD Anderson Cancer Center 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.
Author Interviews, Breast Cancer, Genetic Research / 16.02.2017

MedicalResearch.com Interview with: [caption id="attachment_32075" align="alignleft" width="130"]Dr. med. Rachel Würstlein</strong> Senior Specialist Clinic and Polyclinic for Obstetrics and Gynecology Klinikum der Ludwig-Maximilians-Universität München • Campus Innenstadt Munich Dr. Rachel Wuerstlein[/caption] Dr. med. Rachel Würstlein Senior Specialist Clinic and Polyclinic for Obstetrics and Gynecology Klinikum der Ludwig-Maximilians-Universität München • Campus Innenstadt Munich MedicalResearch.com: What is the background for this study? Response: Gene expression profiles provide important information on the risk of recurrence, and subtyping in HR+ HER2- early breast cancer, in addition to conventional clinicopathological factors. The PRIMe study was performed by the West German Study Group (WSG) and prospectively investigated the impact of the gene expression tests MammaPrint, a 70-Gene Breast Cancer Recurrence Assay, and the corresponding 80-Gene Molecular Subtyping Assay, BluePrint, on adjuvant chemotherapy decisions for early-stage breast cancer patients. To do this, a risk assessment (chemotherapy followed by endocrine therapy, versus endocrine therapy alone) for distant metastasis was performed in 452 patients from 27 study centers using conventional clinicopathological factors such as tumour size and grade first, then compared to the results of the gene expression tests MammaPrint and BluePrint. Doctors and patients then reviewed the results and made a decision on the optimal treatment plan, namely in deciding whether or not patients would benefit from, and should therefore be treated with adjuvant chemotherapy.
ALS, Author Interviews, Genetic Research, JAMA / 15.02.2017

MedicalResearch.com Interview with: Prof. Dr. Christine Van Broeckhoven PhD DSc Professor in Molecular Biology and GeneticsUniversity 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.
Author Interviews, Brigham & Women's - Harvard, Genetic Research, Hearing Loss, Nature / 09.02.2017

MedicalResearch.com Interview with: [caption id="attachment_31894" align="alignleft" width="100"]Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Children's Hospital and Harvard Medical School Boston, MA Dr. Gwenaelle Geleoc[/caption] Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Children's Hospital and Harvard Medical School Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function.
Author Interviews, Diabetes, Genetic Research, JAMA, Race/Ethnic Diversity / 07.02.2017

MedicalResearch.com Interview with: Mary E. Lacy, MPH Department of Epidemiology Brown University School of Public Health Providence, RI MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hemoglobin A1c (A1C) is a blood test that is used to screen for and monitor diabetes. It measures average blood sugar control over the past 2-3 months. A person with sickle cell trait is a carrier for sickle cell disease but often doesn’t have any clinical symptoms. African Americans are more likely than Whites to have diabetes and are more likely to have sickle cell trait. In this article we examined if A1C can be interpreted in the same way in people with and without sickle cell trait. We found that, despite similar results on other measures of blood sugar control, people with sickle cell trait had lower A1C results than people without sickle cell trait. This means that A1C may underestimate diabetes risk in people with sickle cell trait. We also found that, when using standard A1C cutoffs to screen for disease prevalence, we identified 40% fewer cases of prediabetes and 48% fewer cases of diabetes in individuals with sickle cell trait than in those without sickle cell trait. To me, this finding really underscores the potential clinical impact that the observed underestimation of A1C in those with sickle cell trait could have.
ASCO, Author Interviews, Cancer Research, Colon Cancer, Genetic Research, Journal Clinical Oncology / 01.02.2017

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.
Author Interviews, Blood Pressure - Hypertension, Genetic Research / 01.02.2017

MedicalResearch.com Interview with: [caption id="attachment_31612" align="alignleft" width="180"]Helen R Warren PhD</strong> Analysis, Statistics, Genetic Epidemiology Queen Mary, University of London Dr. Helen Warren[/caption] Helen R Warren PhD Analysis, Statistics, Genetic Epidemiology Queen Mary, University of London MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study analysed data from UK Biobank, which is a large cohort including over 500,000 male and female participants from across the UK, aged 40-69 years. We performed a genetic association study for blood pressure, which analysed ~140,000 individuals of European ancestry (as currently interim genetic data is only available for ~150,000 participants). Our study identified 107 genetic regions associated with blood pressure, which had not been previously reported at the time of our analysis. All our new findings were robustly validated within independent replication data resources, comprising a large, total sample size of up to 420,000 individuals.