Author Interviews, Genetic Research, Mental Health Research, PNAS / 22.06.2016 Interview with: Brian W. Haas PhD Department of Psychology Interdisciplinary Neuroscience Graduate Program University of Georgia, Athens, GA What is the background for this study? Response: A burgeoning body of evidence highlights the role of several key genes within the oxytocin signaling pathway linked to sociability. Although many studies strongly supports the role of OXTR in the phenotypic expression of sociability in humans, the roles of other oxytocin pathway genes, such asOXT, has received relatively little attention. (more…)
ASCO, Author Interviews, Breast Cancer, Genetic Research, Journal Clinical Oncology, NIH / 14.06.2016 Interview with: Valentina Petkov, MD, MPH Health Scientist/Program Officer NIH/NCI/DCCPS/Surveillance Research Program What is the background for this study? Dr. Petkov: The number of breast cancer diagnoses is increasing in older patients because of increasing life expectancy and changing population demographics. Despite high incidence, little is known about breast cancer biology and outcomes in patients older than 70, which are often under-represented in clinical trials. The 21-gene Oncotype DX Breast Recurrence Score assay has been used in clinical practice to predict distant recurrence risk and chemotherapy benefit in lymph node negative, hormonal receptor positive (estrogen and/or progesterone receptor positive) invasive breast cancer since 2004. The goal of our study was to evaluate the role of the 21 gene assay in older patients at population level. We used Surveillance Epidemiology and End Results (SEER) data. We included in the analysis 40,134 patients who were diagnosed with invasive breast cancer between 2004 and 2011, had negative nodes and their tumors were hormonal receptor positive and HER2 negative. Breast Cancer Specific Mortality (BCSM) was assessed at 5 years after diagnosis in patients with low risk (Recurrence Score <18), intermediate risk (Recurrence Score 18-30) and high risk (Recurrence Score >30). (more…)
Author Interviews, Autism, Genetic Research / 09.06.2016 Interview with: David Beversdorf, M.D. Associate professor in the departments of radiology, neurology and psychological sciences University of Missouri and Missouri University Thompson Center for Autism and Neurodevelopmental DisordersDavid Beversdorf, M.D. Associate professor in the departments of radiology, neurology and psychological sciences University of Missouri and Missouri University Thompson Center for Autism and Neurodevelopmental Disorders What is the background for this study? What are the main findings? Dr. Beversdorf: Our previous work had demonstrated in retrospective surveys a higher incidence of prenatal psychosocial stress exposure during the late 2nd and early 3rd trimester in pregnancies where the offspring had developed autism spectrum disorder (ASD). This had been confirmed in other studies, including a study examining the timing of exposure to tropical storms during pregnancy. However, not everyone exposed to stress during pregnancy has a child with ASD, so we began to look at genetic risk for augmented stress reactivity. This initial exploration involved examination of the interaction between stress exposure during ASD-associated pregnancies and the maternal presence of variations in one gene well known to affect stress reactivity. Variations in this gene were also targeted as they have been associated with ASD in some studies. We found in two independent groups of patients (one in Missouri, one in Ontario, Canada) that maternal presence of at least one copy of the stress-susceptible variant of this gene is associated with the link between maternal stress exposure during this time window of pregnancy and subsequent development of ASD in the offspring. (more…)
Author Interviews, Genetic Research / 08.06.2016 Interview with: Dr Addolorata Pisconti Ph.D. Department of Biochemistry Institute of Integrative Biology University of Liverpool Liverpool United Kingdom What is the background for this study? Dr. Pisconti: Duchenne muscular dystrophy (DMD) is a genetic disorder caused by lack of the cytoskeletal protein dystrophin which, under normal conditions, protects the muscle fibres during the stress of contraction. In the absence of dystrophin, muscle fibres are more fragile and are easily damaged leading to progressive loss of muscle mass and strength, loss of ambulation, difficulties breathing, cardiomyopathy and eventually premature death. There is no cure for DMD. In Duchenne muscular dystrophy the resident muscle stem cells are impaired and therefore regeneration of damaged muscle fibres is also impaired. Some of the mechanisms leading to impaired muscle stem cell function have been hypothesised, however this remains to date an elusive topic. Chronic inflammation and fibrosis are a hallmark of dystrophic muscle but how they affect muscle stem cells and their regenerative potential remains largely unknown. (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, Kidney Disease, Surgical Research / 07.06.2016 Interview with: David E. Leaf, MD, MMSc, FASN Instructor in Medicine, Harvard Medical School Associate Physician, Renal Division, Brigham and Women's Hospital What is the background for this study? What are the main findings? Dr. Leaf: Heme oxygenase-1 (HO-1), the rate-limiting enzyme in the degradation of heme, has a central role in the pathophysiology of acute kidney injury (AKI) in animal models, but data on HO-1 in human AKI are sparse. Genetic polymorphisms in the number of guanosine thymidine dinucleotide [(GT)n] repeats in the promoter of the HO-1 gene are inversely associated with HO-1 expression, and longer (GT)n repeats are associated with increased cardiovascular events and mortality in a variety of clinical settings. However, no study has evaluated the association between number of (GT)n repeats and risk of AKI in a large cohort of patients. We analyzed the allelic frequencies of (GT)n repeats in the HO-1 gene promoter in 2377 Caucasian patients who underwent cardiopulmonary bypass surgery to evaluate their association with AKI. We categorized patients as having the short (S) or long (L) allele if they had. (more…)
ASCO, Author Interviews, Cancer Research, Genetic Research / 06.06.2016 Interview with: Gregory Idos MD Division of Gastroenterology and Hepatology Keck School of Medicine University of Southern California Los Angeles, CA 90033 What is the background for this study? What are the main findings? Dr. Idos: Identifying individuals at increased risk for hereditary cancer prompts enhanced cancer surveillance as early detection mitigates disease specific morbidity and mortality. This justifies germ line genetic testing for specific cancer risk alleles. In recent years, the field of cancer genetics has moved from a gene by gene sequencing approach to now having the ability to examine multiple genes concurrently. Multiplex gene panel (MGP) testing allows simultaneous analysis of multiple high- and moderate- penetrance genes. As a result, more pathogenic mutations and variants of uncertain significance (VUS) are discovered. MGP tests are increasingly being used by cancer genetic clinics, but questions remain about the clinical utility and complexities of these tests. We are conducting a multi center prospective trial to measure the added yield of detecting pathogenic mutations using the MGP approach. In our interim analysis of the first 1000 participants, we found that multiplex gene panel testing increased the yield of detection of pathogenic mutations by 26%. In some cases, we found patient’s who had a mutation in the BRCA gene, but their family history did not indicate a history of breast or ovarian cancer. (more…)
Author Interviews, Genetic Research, Weight Research / 02.06.2016 Interview with: Dr. Yann C. Klimentidis PhD Assistant Professor Epidemiology and Biostatistics Department The University of Arizona Tucson, AZ 85724 What is the background for this study? What are the main findings? Dr. Klimentidis: There is a large gender disparity in obesity rates among African-Americans. African-American women have much higher rates of overweight and obesity as compared to African-American men. We hypothesized that genetic factors may partly explain this difference. So we tested whether the influence of West-African genetic ancestry on obesity differed among men and women. We found that greater West-African genetic ancestry was associated with protection against central obesity in men, but no such effect was observed in women. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research / 01.06.2016 Interview with: Dr. Nicholas Turner Academic Consultant Medical Oncologist Team leader at the Breakthrough Breast Cancer Research Centre Institute of Cancer Research, London What is the background for this study? What are the main findings? Dr. Turner: Prior laboratory research had identified that gastric cancers with a particular mutation, amplification of the gene FGFR2, were potential sensitive to a drug that inhibits FGFR2. We conducted a trial and showed that gastric cancers with this FGFR2 amplification respond to FGFR inhibition with a drug AZD4547. The amplification is rare, occurring in only a few percent of gastric cancers, so we designed a blood test to identify which patients have the amplification in their cancer, and we are not using the blood test to screen patients for the study. (more…)
Author Interviews, Disability Research, Genetic Research, NEJM / 29.05.2016 Interview with: Dr. Clara van Karnebeek PhD Certified Pediatrician and Biochemical Geneticist at the BC Children’s Hospital Principal Investigator, University of British Columbia What is the background for this study? Dr. van Karnebeek: The goal of the study was to diagnose patients with genetic conditions and discover and describe new diseases with potential for treatment. The study included patients with neurodevelopmental conditions that doctors suspected were genetic or metabolic in origin but had not been diagnosed using conventional methods. Our team tested the children and their parents using a combination of metabolomic (large scale chemical) analysis and a type of genomic sequencing called whole exome sequencing. With this state-of-the-art technique, experts analyze and interpret the portion of DNA called genes that hold the codes for proteins. Some people’s intellectual disability is due to rare genetic conditions that interfere with the processes the body uses to break down food. Because of these metabolic dysfunctions, there is an energy deficit and build-up of toxic substances in the brain and body leading to symptoms such as developmental and cognitive delays, epilepsy, and organ dysfunction. Some of these rare diseases respond to treatments targeting the metabolic dysfunction at the cellular level and range from simple interventions like dietary modifications, vitamin supplements and medications to more invasive procedures like bone marrow transplants. Because the right treatment can improve cognitive functioning or slow or stop irreversible brain damage, early intervention can improve lifelong outcomes for affected children and their families. (more…)
Author Interviews, Dermatology, Genetic Research / 28.05.2016 Interview with: Ryuta Muromoto, Ph.D. Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University Sapporo, Japan What is the background for this study? Dr. Muromoto: Psoriasis is an immune-mediated chronic inflammatory skin disorder that affects some 125 million people worldwide. It is characterized by itchy, scaly skin plaques. It has been known that a cytokine IL-17A, which is produced by immune cells, plays a central role in the development and maintenance of clinical features of psoriasis. IL-17A acts on keratinocytes and up-regulates anti-microbial peptides and a set of chemokines, that are important for immune cell infiltration. This immune cell feedback amplifies psoriatic inflammation. Also, other inflammatory cytokines such as TNF-alpha and interferon-gamma are up-regulated, and have been implicated in pathogenesis of psoriasis. So, the interplay between cytokines appears to be important for development of psoriasis through keratinocyte activation. In this study, we sought to clarify the actual role of IL-17A and its interplay with other cytokines in keratinocyte activation. (more…)
Author Interviews, Depression, Duke, Genetic Research, Mental Health Research, Pediatrics / 27.05.2016 Interview with: Dr. Johnna Swartz, PhD Postdoctoral researcher in the lab of Ahmad Hariri Duke postdoctoral researcher in the lab of Ahmad Hariri What is the background for this study? What are the main findings? Dr. Swartz: Prior research has shown that low socioeconomic status is a risk factor for the development of depression. In this study, we examined whether this risk factor was associated with changes in an epigenetic tag near the gene coding for the serotonin transporter, which has previously been linked to depression. We found that adolescents growing up in families with lower socioeconomic status accumulated more of these tags over time, which may lead to decreased gene expression. Moreover, we found that more of these tags were associated with increased activity in the amygdala, a brain region that plays an important role in the stress response. Finally, we found that adolescents with increased activity in the amygdala were more likely to develop depression symptoms a year later, particularly if they had a close relative with a history of depression. This is some of the first research to draw a link from an environmental risk factor to changes in depression symptoms through changes in epigenetic markers and brain function. (more…)
Author Interviews, Breast Cancer, Genetic Research, Ovarian Cancer / 26.05.2016 Interview with: Sibaji Sarkar Ph.D Instructor of medicine Boston University School of Medicine Boston What is the background for this study? What are the main findings? Dr. Sarkar: Although breast and ovarian cancers have different clinical presentations, there are certain molecular events that are conserved between the two types of cancers. For example, mutation in a few genes, such as BRCA1, BRCA2, is an indicator of possible development of both breast and ovarian cancers. ARHI, a pro-apoptotic imprinted gene is epigenetically silenced in both breast and ovarian cancers. A similar pattern was observed in microRNA as well. There are also several genes which are differentially expressed in these two types of cancers but few of these striking resemblances led us to investigate whether they have a common origin. In this paper, we compared genetic and epigenetic events in both breast and ovarian cancers and we hypothesize that they may have similar origin (mechanism of formation of cancer progenitor cells), which should be regulated by epigenetic mechanism. (more…)
Author Interviews, Diabetes, Genetic Research, Hepatitis - Liver Disease, Weight Research / 24.05.2016 Interview with: Prof-Dr. Annette Schürmann Department of Experimental Diabetology German Institute of Human Nutrition Potsdam-Rehbruecke Nuthetal, Germany What is the background for this study? Dr. Schürmann: The aim of our study was to clarify why genetically identical mice respond very different to a high fat diet. Some of the mice react with an elevated body weight, others not. We analyzed the expression pattern of liver at two time points, at the age of 6 weeks, (the earliest time point to distinguish between those that respond to the diet (responder mice) and those that did not (non-responders)), and at the age of 20 weeks. One transcript that was significantly reduced in the liver of responder mice at both time points was Igfbp2. The reason for the reduced expression was an elevated DNA-methylation at a position that is conserved in the mouse and human sequence. The elevated DNA-methylation of this specific site in human was recently described to associate with elevated fat storage (hepatosteatosis) and NASH. However, as 6 weeks old mice did not show differences in liver fat content between responder and non-responder mice we conclude that the alteration of Igfbp2 expression and DNA methylation occurs before the development of fatty liver. Our data furthermore showed that the epigenetic inhibition of Igfbp2 expression was associated with elevated blood glucose and insulin resistance but not with fatty liver. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research / 14.05.2016 Interview with: Dr. Geoffrey Liu, MD MSC Princess Margaret Hospital/Ontario Cancer Institute University of Toronto Toronto, Ontario Canada What is the background for this study? What are the main findings? Dr. Liu: Cetuximab is a monoclonal antibody therapy used in metastatic colorectal cancer patients when other chemotherapy options have been exhausted. Currently, the only useful biomarker to determine whether metastatic colorectal cancer patients will benefit from the drug, cetuximab, is whether patients carry a RAS mutation in their tumours. We evaluated additional biomarkers using samples from a Phase III clinical trial led by the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group. Our study identified a germline, heritable biomarker, a FCGR2A polymorphism, that further identifies an additional subgroup of patients who would benefit most from receiving cetuximab. This is important because the drug does have toxicity and is expensive to use; patients who are found not to likely benefit from this drug can go on quickly to try other agents, including participation in clinical trials. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, PLoS / 13.05.2016 Interview with: Katarina Truvé PhD Swedish University of Agricultural Sciences and Kerstin Lindblad-Toh Uppsala University What is the background for this study? What are the main findings? Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function. (more…)
Author Interviews, Education, Genetic Research, Nature / 13.05.2016 Interview with: Dr. Daniel J. Benjamin PhD Associate Professor (Research), USC, 2015-present Associate Professor (with tenure), Cornell, 2013-2015 Assistant Professor, Cornell University, 2007-2013 Research Associate, NBER, 2013-present Faculty Research Fellow, NBER, 2009-2013 What is the background for this study? Dr. Benjamin: Educational attainment is primarily determined by environmental factors, but decades of twin and family studies have found that genetic factors also play a role, accounting for at least 20% of variation in educational attainment across individuals. This finding implies that there are genetic variants associated statistically with more educational attainment (people who carry these variants will tend on average to complete more formal education) and genetic variants associated statistically with less educational attainment (people who carry these variants will tend on average to complete less formal education). But none of these genetic variants had been identified until our 2013 paper on educational attainment. That paper, which studied a sample of roughly 100,000 individuals, identified 3 genetic variants associated with educational attainment, each of which has a very small effect. In the current paper, we expanded our sample to roughly 300,000 individuals, with the goal of learning much more about the genetic factors correlated with educational attainment. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, MD Anderson / 11.05.2016 Interview with: Dr. Han Liang PhD Associate Professor and Deputy Department Chair, Department of Bioinformatics and Computational Biology The University of Texas MD Anderson Cancer Center Faculty Member, Baylor College of Medicine Houston, TX MedicalResearch: What is the background for this study? What are the main findings? Dr. Liang: An individual’s sex has been long recognized as a key factor affecting the risk of cancer development and management. However, previous studies on the sex effect have been limited to individual genes, single molecular data types, and single cancer lineages. We performed a comprehensive analysis of molecular differences between male and female patients in a diversity of cancer types and revealed two sex-effect groups. One group contains a small number of sex-affected genes, whereas the other shows much more extensive sex-biased molecular signatures. More than half of clinically actionable genes (e.g., therapeutic targets or biomarkers) show sex-biased signatures. (more…)
Author Interviews, Genetic Research, Nature / 10.05.2016 Interview with: Serena Nik-Zainal MD PhD Wellcome Beit Fellow & Honorary Consultant in Clinical Genetics CDF Group Leader Wellcome Trust Sanger Institute United Kingdom What is the background for this study? What are the main findings? Dr. Nik-Zainal: We have used the massive improvement in speed of "sequencing" (reading the human genetic material) in order to obtain comprehensive whole genome maps of 560 human breast cancer patients. This is the largest whole genome sequencing study of a single cancer type in the world. We wanted to forensically search these cancers, find all the important genes that drive breast cancer, find all the important mutation patterns that tell us something about why breast cells turn into cancer cells and then to pull it altogether for each patient. We wanted to be able to "profile" each cancer patient, to see if we could further our understanding of personal cancer genomes. In all, we had 556 female and four male patients, and they were sought from all over the world – USA, Europe and Asia. (more…)
Author Interviews, BMJ, Diabetes, Genetic Research / 08.05.2016 Interview with: Wenpeng You, PhD student Biological Anthropology and Comparative Anatomy Research Unit University of Adelaide | School of Medicine Adelaide, Australia  Maciej Henneberg, PhD, DSc, FAIBiol Wood Jones Professor of Anthropological and Comparative Anatomy University of Adelaide School of Medicine; Institute for Evolutionary Medicine, University of Zurich Editor in Chief, Journal of Comparative Human Biology HOMO What is the background for this study? What are the main findings? Response: Type 1 diabetes disease has very strong genetic background. Prevalence of type 1 diabetes has been increasing globally. Previous studies focusing on regional genetics and environmental factors cannot fully explain this phenomenon. Due to insufficient medical knowledge up until early 20th century, people with type 1 diabetes disease would most commonly die during their teens or early 20s. Therefore, they did not have the opportunity to pass on their genes providing background for the development of type 1 diabetes to their next generations. Since discovery and introduction of insulin to modern medicine in early 1920s, more and more type 1 diabetes patients have been able to survive their reproduction cycle (up until and past 50 years of age). This has made more and more genes related to type 1 diabetes to accumulate in human populations. We applied the Biological State Index which measures a probability to pass genes on to the next generation at population level.  We found that the rapid increase in type 1 diabetes over the last few decades was correlated with increases of the Biological State Index and its proxy, human life expectancy, especially in more developed world in which natural selection has been relaxed most. This correlation was found after statistically excluding differences in countries income, levels of urbanization, sugar consumption and obesity prevalence. (more…)
Author Interviews, Genetic Research, MD Anderson, Pain Research / 05.05.2016 Interview with: Hui-Lin Pan, MD, PhD Helen T. Hawkins Distinguished Professor and Deputy Division Head for Research Division of Anesthesiology and Critical Care, Unit 110 The University of Texas MD Anderson Cancer Center Houston, TX What is the background for this study? Dr. Hui-Lin Pan: Chronic nerve pain caused by damage to the peripheral nerve is a debilitating health problem and remains very difficult to treat. Sensory neurons in the spinal cord are normally inhibited by inhibitory neurotransmitters (GABA and glycine) to regulate transmission of painful information. A major feature of nerve injury-induced chronic pain is reduced spinal cord inhibition, resulting from diminished activity of a chloride transporter called KCC2. In this study, we investigated whether increasing KCC2 expression at the spinal level using a lentiviral vector can restore KCC2 activity, thereby reducing chronic nerve pain. (more…)
Author Interviews, Genetic Research, Science / 04.05.2016 Interview with: Lluís Ribas de Pouplana, Ph.D IRB Barcelona Barcelona 08028 What is the background for this study? What are the main findings? Response: Ever since the discovery of the genetic code it became obvious that the system had not grown to its full theoretical potential of making proteins with 63 different amino acids. Francis Crick called the code 'a frozen accident', but it was unclear what had actually froze it. In this article we offer an explanation to that, and we validate it experimentally. What we find is that the central pieces of the genetic code, the transfer RNAs, are unable to incorporate enough specific elements for the system to be able to use 63 of them without confusion. Since you need a new tRNA for each new amino acid, once the tRNA identification limit is reached you also reach the maximum number of usable amino acids. This limit happened to be reached at 20, and that's where it has stayed for 3 billion years. (more…)
Addiction, Author Interviews, Genetic Research, PNAS / 29.04.2016 Interview with: Shelly B. Flagel, PhD Molecular and Behavioral Neuroscience Institute Department of Psychiatry University of Michigan, Ann Arbor, MI 48109 What is the background for this study? What are the main findings? Dr. Flagel: We used a unique genetic animal model to examine individual differences in addiction liability. This model of selectively bred rat lines allowed us to examine the brains of “addiction-prone” and “addiction-resilient” rats before and after they were exposed to cocaine. I mportantly, even though all rats were exposed to the same amount of drug, only a certain subset exhibited addiction-like behavior. We focused our neurobiological analyses on two molecules that have been previously implicated in response to drugs of abuse – the dopamine D2 receptor and fibroblast growth factor (FGF2). We examined gene expression and the epigenetic regulation of these molecules and found that low levels of FGF2 in the core of the nucleus accumbens, a brain region known for regulating motivated behavior, may protect individuals from becoming addicted; whereas low levels of D2 in this brain region may predispose individuals to addiction. Further, this is the first study to show that epigenetic modulation of these molecules may be a predisposing factor and that, the epigenetic regulation of D2 may be especially important in susceptibility to relapse. (more…)
Author Interviews, Breast Cancer, Compliance, Genetic Research, Mammograms / 27.04.2016 Interview with: Stamatia Destounis, MD, FSBI, FACR Elizabeth Wende Breast Care, LLC, Clinical Professor of Imaging Sciences University of Rochester School of Medicine and Dentistry  Rochester NY 14620 What is the background for this study? What are the main findings? Dr. Destounis: Identification of women who have an increased risk of breast cancer is important, as they are often eligible for additional screening methods, such as breast MRI. One criterion for eligibility for screening breast MRI is >20% lifetime risk of breast cancer, as determined by risk assessment models through genetic counseling. At my facility, we have incorporated a genetics program. Through the program we are flagging and identifying a large volume of patients who are potentially eligible for additional services. This study was conducted to determine the value of screening MRI in the patient subgroup who have undergone genetic counseling at my facility. In this group we found 50% of patients who were referred for counseling were also recommended to have screening MRI. However, only 21.3% of those recommended actually pursued the exam. Of those patients who did have a screening MRI, 4 were diagnosed with breast cancer, all of which were invasive and node negative. We ultimately had a 10% biopsy rate and 50% cancer detection rate in this subgroup. (more…)
Author Interviews, Genetic Research, PLoS, Vitamin D / 27.04.2016 Interview with: Haidong Zhu, MD, PhD Associate Professor of Pediatrics Georgia Prevention Institute Medical College of Georgia Augusta University What is the background for this study? What are the main findings? Dr. Zhu: Vitamin D plays an important role in a wide range of body functions beyond bone health. Vitamin D deficiency is associated with increased risk of cancer and cardiovascular disease. Vitamin D deficiency is common among darker skin individuals, particularly African-Americans, which could contribute to health disparity. We want to understand underlying molecular mechanism (i.e. global DNA methylation) for how vitamin D deficiency causes cancer, cardiovascular disease and impaired immune function. DNA methylation, a chemical modification to our genome, is one of the ways that our body adapts to the environment. Low rate of global DNA methylation is a common event in cancer, which may lead to disturbances in the genome, make the genome more vulnerable to environmental damage and increase disease risk. Our study shows that majority of black teens are vitamin D deficient and have a lower rate of global DNA methylation than white teens. We further demonstrate that vitamin D3 supplementation for 16 weeks increases global DNA methylation in black teens and young adults. Our study provides an important piece of evidence that vitamin D plays a role in epigenetic regulation in humans, which could be an underlying mechanism for vitamin D-deficiency related disease risk and health disparity. (more…)
AACR, Author Interviews, Cancer Research, Genetic Research, MD Anderson, Weight Research / 20.04.2016 Interview with: Dr. Xifeng Wu, MD PhD Department Chair, Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences Director, Center for Translational and Public Health Genomics Professor, Department of Epidemiology Division of Cancer Prevention and Population Sciences The University of Texas MD Anderson Cancer Center, Houston, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Wu: Obesity is a well-established risk factor for renal cell carcinoma (RCC), the most common form of kidney cancer. It has been estimated that more than 40% of RCC incident cases in the US may be attributed to excessive body weight. Growing body of evidence suggests that obesity may also influence clinical outcome of RCC; however, the findings are sometimes conflicting. So far, the molecular mechanism linking obesity to RCC risk or prognosis is not well understood. In this study, we evaluated the promoter CpG site methylation of 20 candidate obesity-related genes and their association with RCC risk and recurrence in a two-phase study of 240 newly diagnosed, previously untreated RCC patients. Pyrosequencing was conducted on paired RCC tumor and normal adjacent tissues to measure promoter methylation. Among the 20 markers, we found NPY, LEP and LEPR showed significant differential methylation levels between tumors and normal adjacent tissues, and methylation was significantly higher in tumors in both discovery and validation groups. Consistent with our findings, we also found lower expression of LEPR in tumor tissues compared to normal adjacent tissues in data obtained from The Cancer Genome Atlas. Additionally, high LEPR methylation in tumors was associated with more advanced tumor features, such as high pathologic stage, high grade and clear cell RCC histology, and increased risk of recurrence compared to the low methylation group. These results suggest that tissue changes in promoter methylation in obesity-related genes may provide some biological basis for the association between obesity and RCC outcome, and that LEPR may be an independent prognostic indicator of recurrence in RCC patients. Further research in larger study population and functional studies are warranted to validate our findings and to elucidate the underlying causal mechanisms. (more…)
Author Interviews, Exercise - Fitness, Genetic Research / 20.04.2016 Interview with: Nicholas Jones BSc (Hons) MSc ISAK CSCS ASCC DNA Sports Performance Ltd Director What is the background for this study? Response: Coaches and trainers all know that individuals can respond differently to the same stimulus. One person may be a super responder to X training method, another may be a none-responder to the very same training method. The reasons for this have never been fully explained, however genetics have been discussed and thought to play a role for some time. What are the main findings? Response: At the beginning of the eight weeks of training, the participants were set two fitness tests to measure their power and endurance. Power was measured by a countermovement jump (CMJ) and endurance by an aerobic three minute cycle test (known as Aero3). After eight weeks, those whose training had been matched to their genes improved their CMJ power test of 7.4% compared to just a 2.6% increase in the mismatched group. In the cycle endurance test, those who trained to their genetic strengths saw an average 6.2% improvement compared to 2.3% for the mismatched group. (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA, UCSD / 01.04.2016 Interview with: H Kirk Hammond, MD Professor of Medicine (Cardiology) University of California San Diego Veterans Affairs San Diego Healthcare System San Diego, CA 92161 What is the background for this study? Dr. Hammond: Heart failure affects >28 million patients worldwide and is the only cardiovascular disease that is increasing in prevalence. Despite steady improvement in drug therapy for heart failure, recent hospitalization rates and mortality have changed little. New therapies are needed. Adenylyl cyclase type 6 (AC6), is a protein that catalyzes the conversion of ATP to cAMP and is an important determinant of heart function. The amount and function of AC6 are reduced in failing hearts, and preclinical studies have shown benefits of increased cardiac AC6 content on the heart. The aim of the trial was to determine safety and heart function gene transfer of AC6, achieved by intracoronary delivery of an inactivated virus carrying the gene for AC6 (Ad5hAC6) in patients with symptomatic heart failure and reduced ejection fraction. Our hypothesis was that AC6 gene transfer would safely increase function of the failing hearts of patients with heart failure. (more…)