Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Genetic Research, Journal Clinical Oncology, Race/Ethnic Diversity / 20.09.2015

Aditya Bardia MBBS, MPH Attending Physician, Massachusetts General Hospital Cancer Center, Assistant Professor, Harvard Medical School Boston, MA 02114MedicalResearch.com Interview with: Aditya Bardia MBBS, MPH Attending Physician, Massachusetts General Hospital Cancer Center, Assistant Professor, Harvard Medical School Boston, MA 02114   Medical Research: What is the background for this study? What are the main findings? Response:  Multiple studies have consistently shown that African American women with cancer, including breast cancer, have worse outcomes than Caucasian counterparts. While socioeconomic issues, including access to care plays an important role, the contribution of tumor biology has been less clear. In this study, utilizing exome sequencing data, we linked the racial distribution of primary breast cancer with tumor genotypic traits, including somatic mutations, gene-expression profiles and intra-tumor heterogeneity. We observed that in addition to having a higher prevalence of triple negative breast cancer than Caucasian women (something that has been documented in the literature), African American women had a significantly higher prevalence of TP53 mutations, TNBC basal-like 1 and mesenchymal stem-like tumors, and intratumor genetic heterogeneity, and all of which suggest more aggressive tumor biology, suggesting that differences in tumor genomic profile contribute, at least partly, to the known racial disparity in survival between African Americans and Caucasians breast cancer patients. (more…)
Author Interviews, Cancer Research, Case Western, Colon Cancer, Genetic Research / 16.09.2015

Ahmad M. Khalil, PhD Department of Genetics School of Medicine Case Western Reserve University Cleveland, Ohio 44106-4955 MedicalResearch.com Interview with: Ahmad M. Khalil, PhD Department of Genetics School of Medicine Case Western Reserve University Cleveland, Ohio 44106-4955 Medical Research: What is the background for this study? What are the main findings? Dr. Khalil: DNA in human cells is modified chemically by methylation. The process of DNA methylation plays important roles in protecting human DNA and ensures proper gene expression.  In cancer cells, the process of DNA methylation becomes deregulated, however, the mechanisms of how this occurs are not known.  In our study, we have uncovered a novel mechanism on how colon cancer cells change their DNA methylation, and consequently, become more tumorigenic. We specifically identified a long non-coding RNA that interacts with and regulates the enzyme that modifies DNA with methylation - the enzyme is called DNMT1. This lncRNA become suppressed in colon tumors, which we believe is a key step in loss of DNA methylation in colon cancer cells. (more…)
Author Interviews, Dermatology, Genetic Research / 12.09.2015

Thomas N. Darling, MD, PhD Department of Dermatology Uniformed Services University of the Health Sciences Bethesda, MD 20814 MedicalResearch.com Interview with: Thomas N. Darling, MD, PhD Department of Dermatology Uniformed Services University of the Health Sciences Bethesda, MD 20814 Medical Research: What is the background for this study? What are the main findings? Dr. Darling: Many people with tuberous sclerosis complex (TSC) have skin tumors that can bleed or cause distress. Only surgical approaches were useful for treating these skin tumors in the past. Recently, drugs called mTOR inhibitors, including sirolimus, were shown to shrink internal tumors in those affected by tuberous sclerosis complex. We wanted to document what happens to the skin tumors in those being treated with oral sirolimus. We found that most patients taking oral sirolimus showed improvement in their skin tumors, and that these effects were maintained during a couple years of treatment. We did not observe any evidence for the skin tumors becoming resistant to the drug. (more…)
Author Interviews, Genetic Research, Sexual Health / 12.09.2015

MedicalResearch.com Interview with: Binbin Wang, PhD Center for Genetics, National Research Institute for Family Planning Beijing China Medical Research: What is the background for this study? What are the main findings? Dr.Wang:Homosexuality has become an important issue all around the world, as well as in China. Beside of the human right problems it poses, the reality that more and more HIV cases are infected through homosexual activity,especially men who have sex with men (MSM), should be concerned. People are wondering how homosexuality develops. As a genetic researcher, I'd like to find the answers in the field of genetics. This study is based on previous evidence that genes may have impact on homosexuality. Besides, animal models have provided clues that abnormality in some neurotransmitters, such as dopamine, may alter the sex behavior of animals. Therefore, we choose COMT (the gene catechol-O-methyltransferase) as the target, which is important for the synthesis of dopamine. We find that an amino acid residue change in COMT could increase the risk of developing male homosexuality. Our results provide some evidence that male homosexuality is connected with genes. (more…)
Author Interviews, Breast Cancer, Genetic Research, UCSF / 04.09.2015

Dr. Elisa Long PhD Assistant professor UCLA Anderson School of ManagementMedicalResearch.com Interview with: Dr. Elisa Long PhD Assistant professor UCLA Anderson School of Management Medical Research: What is the background for this study? What are the main findings? Dr. Long: The study was motivated by my own diagnosis of triple-negative breast cancer last year, at the age of 33. I also learned that I carried a BRCA1 mutation, despite no family history. As a patient, I would have benefitted tremendously from a universal BRCA screening program, but as a health services researcher, I had to ask if indiscriminate screening of all women in the U.S.—where only 1 in 400 carry a mutation—is a good use of resources. Using a previously published decision analytic model, we calculated the cost-effectiveness of universal BRCA screening. We find that compared to screening based on family history, it is not cost-effective, assuming a test price of $2,000 to $4,000. However, as the price of genetic testing continues to fall, as indicated by the $249 test now offered by Color Genomics, universal BRCA screening becomes much more affordable. Additionally, population screening of Ashkenazi Jewish women—among whom 1 in 50 carry a BRCA mutation—is very cost-effective, because the chances of finding a carrier are much higher. (more…)
Author Interviews, Genetic Research, Pediatrics, Psychological Science / 02.09.2015

Beate W. Hygen PhD Student Department of Psychology Norwegian University of Science and Technology Social ScienceMedicalResearch.com Interview with: Beate W. Hygen PhD Student Department of Psychology Norwegian University of Science and Technology Social Science Medical Research: What is the background for this study? Response: The study is part of the Trondheim Early Secure Study (TESS) conducted at the  Department of Psychology, Norwegian University of Science and Technology (NTNU) and NTNU Social Science. The main aim of TESS is to detect risk and protective factors with regards to children’s mental health and well-being.  TESS examines multiple factors which may play a role in children`s development. There is substantial research, based on diathesis-stress theorizing, indicating that some individuals, including children, are more susceptible to the negative effects of contextual adversity than are others. However, according to differential susceptibility theory, such "vulnerable" individuals may also be the ones that benefit the most from positive environmental conditions. Thus, some individuals are more malleable for "better and for worse" to environmental exposures. The article Child exposure to serious life events, COMT, and aggression: Testing differential susceptibility theory was designed to examine if the COMT polymorphism moderated the effect of early-life adversity on aggressive behavior. Thus, we sought to competitively evaluate which model of person X environment interaction best accounted for the anticipated differential effects of life event stress on children's aggressive behavior. (more…)
Author Interviews, Cancer Research, Genetic Research / 02.09.2015

Sameek Roychowdhury, MD, PhD Assistant Professor, Internal Medicine, College of Medicine Assistant Professor, Department of Pharmacology, College of Pharmacy Department of Internal Medicine Division of Medical Oncology Wexner Medical Center The Ohio State UniversityMedicalResearch.com Interview with: Sameek Roychowdhury, MD, PhD Assistant Professor, Internal Medicine, College of Medicine Assistant Professor, Department of Pharmacology College of Pharmacy Department of Internal Medicine Division of Medical Oncology Wexner Medical Center The Ohio State University Medical Research: What is the background for this study? What are the main findings? Dr. Roychowdhury: Precision cancer medicine is a new paradigm to match patients to therapies based on the molecular alterations in their cancer. Novel genomic testing of cancer using next generation sequencing can reveal numerous mutations for each patient across many genes and types of cancer, and this requires detailed time-intensive interpretation. Driver mutations can confer a selective growth or survival advantage to cancer cells, while passenger mutations do not. Cancer Driver Log, or CanDL, is meant to aid interpretation of mutations by providing the latest literature evidence for individual driver mutations, and thereby aiding pathologists, lab directors, and oncologists in interpreting mutations found in their patient’s cancer. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research / 02.09.2015

Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C. Medicalresearch.com Interview with: Roger Packer MD Senior Vice President Center for Neuroscience & Behavioral Health Children's National Medical Center Washington, D.C.   MedicalResearch: What is the background for this study? What are the main findings? Dr. Packer: The background is that medulloblastoma is the most common childhood malignant brain tumor. It carries with it a variable prognosis. For some subsets of patients, with current available treatment which includes surgery, radiation and chemotherapy, we see survival rates as high as 90% (and often cures) 5 years following diagnosis and treatment. However, for some subsets of patients, survival rates are much poorer, in those with higher risk characteristics as low as 40% at 5 years. Current treatment also carries with it a significant risk for long term sequelae, including intellectual loss secondary to radiation therapy and persistent, at times devastating neurologic complications such as unsteadiness. To try to improve our understanding and ultimately our therapy for medulloblastoma, an international working group has shared patient specimens and patient information to attempt to determine what the molecular predictors of outcome are for children with medulloblastoma and if such molecular genetic findings can be used to develop better, safer therapies. Children’s National is part of this international collective of institutions, which published this and other studies. The main findings of this study are that complex, integrated genetic analysis of tumor specimens can be used to better understand and set the scene for better treatment of medulloblastoma.  Medulloblastoma can be broken into relatively distinct, molecular subtypes each with its own prognosis and potential therapy. A major finding of this study was that within a given tumor, different areas showed the same molecular genetic pattern. The importance of this is that since the tumors are relatively the same in different areas, molecularly-targeted therapies have an excellent chance of working on the entire tumor, resulting in better tumor control and safer treatments. (more…)
Author Interviews, Case Western, Dermatology, Genetic Research / 27.08.2015

Nely Aldrich, MD Department of Dermatology University Hospitals Case Medical CenterMedicalResearch.com Interview with: Nely Aldrich, MD Department of Dermatology University Hospitals Case Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Aldrich:   To our knowledge, no formal studies have been performed on the genetic vs. environmental factors that lead to the development of rosacea. Our department has the unique opportunity to attend the Twins Days festival in Twinsburg, Ohio. This is a yearly festival where thousands of twin pairs come from all over the world. This was the perfect setting to ask our research question. Our main finding was that there is an approximately 50% contribution of genetics to rosacea and the other 50% can be attributed to environmental factors. Sun exposure, smoking, alcohol use, skin cancer history, and heart disease were also found to be correlated with a higher rosacea severity. (more…)
Author Interviews, Breast Cancer, Genetic Research, Race/Ethnic Diversity / 26.08.2015

Tuya Pal MD Division of Population Sciences Department of Health Outcomes and Behavior Moffitt Cancer Center Tampa, Florida MedicalResearch.com Interview with: Tuya Pal MD Division of Population Sciences Department of Health Outcomes and Behavior Moffitt Cancer Center Tampa, Florida   Medical Research: What is the background for this study? Dr. Pal:  Young Black women bear a disproportionate burden associated with breast cancer incidence and mortality compared to their White counterparts. Given that inherited mutations in the BRCA1 and BRCA2 genes are more common among young breast cancer survivors, we questioned to what extent mutations in these genes might contribute to the racial disparity in breast cancer incidence among young women. Medical Research: What are the main findings? Dr. Pal:  Through conducting the largest U.S. based study of BRCA mutation frequency in young black women diagnosed with breast cancer at or below age 50, we discovered they have a much higher BRCA mutation frequency than that previously reported among young white women with breast cancer.  Specifically, of the 396 Black women with breast cancer diagnosed at or below age 50, 12.4% had mutations in either BRCA1 or BRCA2.  Furthermore, over 40 percent of those with a mutation had no close relatives with breast or ovarian cancer, which suggests that family history alone may not identify those at risk for carrying a BRCA mutation.  (more…)
Author Interviews, Genetic Research / 21.08.2015

Hendrik Marks Ph.D Group leader Epigenetics of Stem Cells Radboud University, Department of Molecular Biology, RIMLS, Nijmegen, The Netherlands MedicalResearch.com Interview with: Hendrik Marks Ph.D Group leader Epigenetics of Stem Cells Radboud University, Department of Molecular Biology, RIMLS Nijmegen, The Netherlands   Medical Research: What is the background for this study? What are the main findings? Dr. Marks: In mammals, sex is determined by two so-called "sex" chromosome: males have a single X chromosome as well as a Y chromosome, whereas females have two copies of the X chromosome. However, if both X chromosomes were to be active in female cells, these cells would have a double dosis of X-chromosomal gene products as compared to male cells. As this is lethal for almost all cells, female cells shut off one X chromosome in every cell in a process called X inactivation. This process occurs during early embryonic development. A lot is known about how this process is turned on, but is was unclear how such a silencing process spreads along a full chromosome. In order to further study this, we used female mouse embryonic stem cells (mESCs) as a model system and initiated X inactivation by means of differentiation. With the latest technologies, we were able to keep the two X chromosomes apart and measure one of them – with its 166 million base pairs (Mbs) – in detail. Every day we checked which parts of the chromosome had been switched off. The whole process took about eight days, and the inactivation spreads out from the centre of the X chromosome towards the ends. That doesn’t happen gradually but moves jumpwise from domain to domain. Domains are long pieces of DNA (of around 1Mb) that cluster together in knots. As it seems that X inactivation jumps from domain to domain, we now know that these domains are co-regulated. Also, we collected strong evidence that the same process is occurring in human. (more…)
Author Interviews, Education, Genetic Research, Social Issues / 21.08.2015

Ben Domingue Assistant Professor (starting 9/2015) Stanford Graduate School of Education   MedicalResearch.com Interview with: Ben Domingue Assistant Professor (starting 9/2015) Stanford Graduate School of Education     Medical Research: What is the background for this study? What are the main findings? Response: Earlier research has started to illuminate which genetic variants are associated with educational attainment. Subsequent work has taken these variants, combined them into a "polygenic score", and studied how that polygenic score predicts educational attainment. Our research continues this line of inquiry by examining the predictive performance of that polygenic score in a representative sample of US adults who are now in their 30s. A few notable findings include that: (A) the polygenic score predicts educational attainment in the African Americans in our sample and (B) that the polygenic score is associated with neighborhood characteristics. As with earlier research, we are able to show that the higher score sibling from within a family will complete more years of schooling (on average) than their lower score co-sib. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA, Ovarian Cancer / 13.08.2015

Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114MedicalResearch.com Interview with: Leif W. Ellisen, M.D., Ph.D Professor of Medicine, Harvard Medical School Program Director, Breast Medical Oncology Co-Leader, Breast Cancer Program MGH Research Scholar MGH Cancer Center Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Dr. Ellisen: The traditional approach to genetic testing for women with suspected hereditary breast and/or ovarian cancer risk is to test for BRCA1 and BRCA2 alone. Recent studies have shown that testing with a multi-gene panel finds relevant risk gene mutations in substantially more women than does testing for BRCA1 and BRCA2 alone. However, one of the concerns about broader multi-gene testing has been that the results really wouldn’t change what you told women about their risk and management – either because the risk associated with the other genes may not be as high as for BRCA1/2, or because the clinical practice guidelines associated with some of the other genes are less specific. Our study sought to determine how often testing such women using a multi-gene panel would find mutations in genes other than BRCA1/2, and more importantly to ask whether finding those mutations would change how you would manage the patient and their family. We found that multi-gene panel testing finds relevant risk gene mutations in substantially more women (approximately 40% more) than does testing for BRCA1 and BRCA2 alone. Furthermore, in a case-by-case analysis we showed that finding mutations in these other genes is likely to change the clinical management that is considered or recommended for the majority of the mutation-positive women and their families.  Notably, our analysis of the predicted management change is based not just on the gene mutation alone, but on how the gene appears to be behaving in that particular family. (more…)
Author Interviews, Genetic Research, NYU, PLoS / 08.08.2015

Dr. Arthur Caplan Ph.D. Drs. William F and Virginia Connolly Mitty Professor Head of the Division of Medical Ethics New York University, Langone Medical Center, NYMedicalResearch.com Interview with: Dr. Arthur Caplan Ph.D. Drs. William F and Virginia Connolly Mitty Professor Head of the Division of Medical Ethics New York University, Langone Medical Center, NY Medical Research: What is the background of the Down Syndrome Prenatal Education Act? Dr. Caplan: For many years women who  receive a positive prenatal test for Down syndrome have been aborting their pregnancies.  Rates of pregnancy termination, while somewhat disputed, are very high.  In the USA, UK and Denmark they have consistently been over 80% for many years.   This has led some parents of children with Down to wonder if the counseling that women receive is biased negatively against a life with Down. They working with pro life legislators in many states have promoted legislation to insure that mothers carrying an infant with a diagnosis of Down Syndrome have access to positive information and helpful resources about life with a child with Down.  This legislation has been enacted in many states and there is a Federal law as well. Medical Research: How does Chloe's Law impact genetic testing? Dr. Caplan: These laws represent a seismic shift in counseling about genetic disorders and diseases.  Historically counselors aspired to be value-free—simply trying to provide objective information to their patients/clients.  With laws like Chloe’s the public is saying they do not trust the neutrality of counselors and counseling and want more positive messages sent about Down.  This is quite simply an ethical revolution in how counseling for Down will be done in the future.  It is also a direct Challenge to the legitimacy of value-neutrality as a counseling norm that certainly will be extended to other conditions and disabilities where abortion rates are high and where there is the belief that there is unjustified prejudice or bias against disabilities among those working in clinical genetics. (more…)
Author Interviews, Cancer Research, Genetic Research / 02.08.2015

Christos Nikolaidis Ph.D. Laboratory of Pharmacology Medical School, Democritus University of Thrace Dragana, Alexandroupolis GreeceMedicalResearch.com Interview with: Christos Nikolaidis Ph.D. Laboratory of Pharmacology Medical School, Democritus University of Thrace Dragana, Alexandroupolis Greece Medical Research: What is the background for this study? Response: Epigenetic changes are part of the natural history of cervical neoplasia. Tracking these changes at the molecular level is necessary for understanding disease progression, response to treatment and prognosis. Epigenetic biomarkers can potentially assess the stage of cervical intraepithelial neoplasia (CIN). This information can be used for screening purposes, to improve the overall quality of cervical cancer diagnostics. Medical Research: What are the main findings? Response: Paired boxed 1 (PAX1) gene methylation status has been widely used as a biomarker for cervical cancer screening.  We have conducted a meta-analysis of the diagnostic test accuracy of PAX1 methylation, on moderate cervical dysplasia or worse (CIN2+) versus normal epithelium, and severe cervical dysplasia or worse (CIN3+) versus normal epithelium, for a total population of 1385 women. The results of this assay were generally satisfactory for CIN2+ vs normal, and extremely satisfactory for CIN3+ vs normal (Sensitivity=0.77, Specificity=0.92, AUC=0.931). This raises the possibility of utilizing this biomarker to improve current diagnostic protocols. (more…)
Author Interviews, Genetic Research / 01.08.2015

Dr. Rosalind Arden Centre for Philosophy of Natural & Social Science London School of Economics LondonMedicalResearch.com Interview with: Dr. Rosalind Arden Centre for Philosophy of Natural & Social Science London School of Economics London MedicalResearch: What is the background for this study? What are the main findings? Dr. Arden: We've known for a while that people who score higher on IQ-type tests tend to live longer. A study published in the British Medical Journal (Whalley & Deary, 2001) examined intelligence in childhood and later survival. People born in Scotland in 1921 took an IQ-type test at age 11 in 1932. Those with higher test scores were more likely to survive to age 76. What we haven't known is 'why?' One possibility is that advantages from being raised in a wealthier family may enhance intelligence and health - leading to brighter people living longer. Another possibility is that many genes that influence brains also influence bodies. If well-built brains co-occur with well-built bodies, that could also explain the link. These are only two of several possible explanations. We aimed to test whether genes caused the link between intelligence and life-expectancy. We found 1) the link between intelligence and life expectancy is positive but small. 2) The cause of the link is almost all genetic. We found this by examining differences within twin pairs. Twins offer a quasi-natural experiment because they share many features of the environment that are often thought (mistakenly) to cause differences between people. And marvelously, for science there are two kinds of twins, with known genetic relatedness (100 % or 50%). This give us a means to test questions about the cause of differences in a population, as well as the causes of correlations among traits within a population. (more…)
Author Interviews, Cancer Research, Genetic Research, MD Anderson / 24.07.2015

Eduardo Vilar-Sanchez, MD, PhD Assistant Professor, Department of Clinical Cancer Prevention Division of OVP, Cancer Prevention and Population Science The University of Texas MD Anderson Cancer Center Houston, TX 77030MedicalResearch.com Interview with: Eduardo Vilar-Sanchez, MD, PhD Assistant Professor, Department of Clinical Cancer Prevention Division of OVP, Cancer Prevention and Population Science The University of Texas MD Anderson Cancer Center Houston, TX 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Vilar-Sanchez: I am a physician scientist at The University of Texas MD Anderson Cancer Center (MDA), a medical oncologist specializing in cancer genetics, especially colorectal cancer (CRC) syndromes. At MD Anderson, I have medical practice consisting primarily of colorectal cancer, as part of the clinical cancer arm of MD Anderson. I became interested in this topic because it is now well recognized that colorectal cancer is increasing in prevalence in young individuals. CRC is the third most common cancer in the US with 90% diagnosed in patients older than 50. While most CRC patients develop cancer in their 60s or 70s, the incidence is now rising in individuals younger than 50. Over the next two decades, it is projected that the incidence of CRC in young adults under 35 will double. Only 5% of all CRC patients have a known hereditary predisposition cancer syndrome. Patients diagnosed at or under age 35 represent an extreme phenotypic presentation, constituting only 1.5% of all CRC cases. We retrospectively reviewed all patients with CRC patients age 35 or under, who were evaluated by the Genetic Services group at MD Anderson. In this group, a surprising 30% had a recognized hereditary cancer syndrome, a marked increase compared to the general CRC population. (more…)
Author Interviews, Genetic Research, Heart Disease / 24.07.2015

MedicalResearch.com Interview with: Dr. Paraskevi Christofidou Department of Cardiovascular Sciences, University of Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Leicester UK MedicalResearch: What is the background for this study? Dr. Christofidou: Homozygosity arises when identical alleles are present on both chromosomes. Runs of homozygosity (ROHs) are very long segments of uninterrupted sequences of homozygous variants across the human genome. Runs of homozygosity represent "re-union" of pieces from DNA from parents in their children. The two DNA copies are identical because have been inherited from a common ancestor somewhere in the distant past. Runs of homozygosity are recognized signature of recessive inheritance, because they allow unmasking of recessive variants. Recessive variants only show their effect when present on both chromosomes of an individual's genome. Some of these ROHs may potentially harbor variants that exert their pathological effects in the homozygous recessive state. This is important because it helps us better understand the consequences of the recessive model of inheritance in relation to complex diseases. Coronary artery disease (CAD) is a terminal clinical manifestation of cardiovascular disease and is the leading cause of death worldwide and is the UK's single biggest killer. Nearly one in six men and one in ten women die from CAD. Coronary artery disease is a complex, multifactorial disorder originating from a complicated interplay of multiple genetic and environmental factors. Contributions of ROHs to the genetic architecture of CAD are not known. The primary goal of this project was a comprehensive analysis of association between genome-wide homozygosity measures and CAD in individuals of white European ancestry. A secondary aim was to explore the association of ROHs and gene expression in human monocytes and macrophages. MedicalResearch: What are the main findings? Dr. Christofidou: Our analysis of 24,320 individuals from 11 populations of white European ethnicity revealed statistically significant differences in homozygosity levels between individuals with Coronary artery disease and control subjects. On average, individuals with CAD had 0.63 ROHs more than control subjects. The average total length of ROHs was approximately 1046.92 kb greater in individuals with CAD than control subjects. We were able to qualify a measure of genome-wide homozygosity levels in relation to CAD - an estimated 13% increase in CAD per 1 standard deviation increase in the proportion of the autosomal genome covered by ROHs. Individual ROHs showed significant associations with monocyte and macrophage expression of genes located nearby. These associations suggest that many ROHs might be signatures of biologically active recessive variants with a potential to regulate transcription. (more…)
Author Interviews, Genetic Research, Heart Disease, McGill / 20.07.2015

Christopher Labos MD CM, MSc FRCPC Division of Epidemiology, Biostatistics and Occupational Health McGill University Montreal, Quebec CanadaMedicalResearch.com Interview with: Christopher Labos MD CM, MSc FRCPC Division of Epidemiology, Biostatistics and Occupational Health McGill University Montreal, Quebec Canada Medical Research: What is the background for this study? What are the main findings? Response: There have been great advances in the field of genetics in recent years. Especially in cardiology, a number of genetic variants have been identified that are associated with cardiovascular disease. But it is not clear how useful these variants are in terms of predicting future evens in patients that have already suffered a myocardial infarction. What we found in our study is that a genetic risk score composed of the 30 most common genetic variants associated with cardiovascular diseases was not useful in predicting recurrent events in the first year after a patient suffered a myocardial infarction. (more…)
Author Interviews, Genetic Research, Ophthalmology / 17.07.2015

Professor Robert E MacLaren MB ChB DPhil FRCOphth FRCS Nuffield Laboratory of Ophthalmology Nuffield Department of Clinical Neurosciences, University of Oxford Oxford Biomedical Research Centre, University of Oxford, Oxford, UK Moorfields Eye Hospital & UCL NIHR Biomedical Research Centre for Ophthalmology London, UK.MedicalResearch.com Interview with: Professor Robert E MacLaren MB ChB DPhil FRCOphth FRCS Nuffield Laboratory of Ophthalmology Nuffield Department of Clinical Neurosciences Oxford Biomedical Research Centre, University of Oxford, Moorfields Eye Hospital & UCL NIHR Biomedical Research Centre for Ophthalmology London, UK.
Medical Research: What is the background for this study? What are the main findings? Prof. MacLaren: The study shows that gene therapy can be used to release a protein in the eye that arrests the development of retinitis pigmentosa, a blinding disease caused by degeneration of the retina. The study was performed in mice which had a similar genetic defect to that found in humans with the disease. The mice also had fluorescent green “glow in the dark” light sensing cells known as cones, which we could see and count by looking into the eye – like counting stars in the night sky. By counting the green fluorescent cones we were able to work out the exact dose of gene therapy needed to keep these cells alive indefinitely. The study was funded by Fight for Sight, a UK charity that supports finding cures for eye diseases. (more…)
Author Interviews, Genetic Research, Surgical Research, Yale / 17.07.2015

John A. Elefteriades, MD William W.L. Glenn Professor of Surgery Chief of Cardiothoracic Surgery Director, Aortic Institute at Yale-New Haven Yale University School of MedicineMedicalResearch.com Interview with: John A. Elefteriades, MD William W.L. Glenn Professor of Surgery Chief of Cardiothoracic Surgery Director, Aortic Institute at Yale-New Haven Yale University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Elefteriades: The race to map the human genome was declared completed in 2003, at a cost of 3 billion dollars for the international collaborative university group and 300 million dollars for Craig Venter at Celera. Whole exome sequencing can now be performed at a cost of only several thousand dollars per individual. So, whole exome sequencing (also called Next Generation Sequencing) can now be applied to understand and treat diseases of many organ systems. In this study, we applied whole exome sequencing to study over 100 patients with thoracic aneurysm. In the late 1990s, both Dr. Diana Milewicz in Texas and our group at Yale had determined that many thoracic aortic aneurysms were genetically transmitted. Dr. Milewicz went on to identify many of the causative mutations. In this study, we were able to look, by whole exome sequencing performed on saliva, for all 21 mutations known to cause thoracic aortic aneurysm--all at one time in one comprehensive genetic test. We were able to protect patients with the most serious discovered mutations by early surgery, the need for which could not otherwise have been apparent.  (more…)
Author Interviews, Biomarkers, Cancer Research, Mayo Clinic, MD Anderson, Nature / 18.06.2015

Eric Jonasch, MD Associate Professor Department of Genitourinary Medical Oncology University of Texas MD Anderson Cancer Center Houston, TXMedicalResearch.com Interview with: Eric Jonasch, MD Associate Professor Department of Genitourinary Medical Oncology University of Texas MD Anderson Cancer Center Houston, TX and Dr. Thai H. Ho, MD Ph.D. Department of Oncology Mayo Clinic Scottsdale ArizonaDr. Thai H. Ho, MD Ph.D. Department of Oncology Mayo Clinic Scottsdale Arizona Medical Research: What is the background for this study? What are the main findings? Response: The blueprints of a cell are encoded in DNA strands (its genome) which are highly compressed in order to fit into a tiny cell. The reading (called the epigenome) of these DNA ‘blueprints’ determines whether that cell will develop into a kidney cell or another type of cell. However, in cancer, errors occur either in the blueprints themselves or the cell makes mistakes in reading the blueprints. Cancers of the kidney affect more than 61,000 patients annually and over 13,000 patients die annually, making it one of the top 10 leading causes of cancer deaths. Studies have revealed that mutations occur in genes that regulate how our DNA ‘blueprints’ are compacted in greater than >50% of kidney cancers, making these genes as a group the most frequently mutated. In our study, we identified that these errors that initially arise in an early kidney cancer lead to propagation of these same errors in metastases, a phenomenon in which the cancer has spread to another organ and is a major cause of death. Furthermore, we generated a detailed map of these epigenomic changes in patient-derived tumors. (more…)
Author Interviews, Breast Cancer, Duke, Genetic Research, JAMA / 11.06.2015

Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North CarolinaMedicalResearch.com Interview with: Michaela Dinan, Ph.D. Duke Clinical Research Institute and Duke Cancer Institute Department of Medicine Duke University School of Medicine Durham, North Carolina Medical Research: What is the background for this study? What are the main findings? Response: I think it will be critical to further explore the implications of Oncotype DX breast cancer assay (ODX testing) in women with breast cancer.  The ODX test helps predict which cancers will be more aggressive as well as guide recommendations as to which patients would most likely benefit from chemotherapy. I think we should look to see what impact this test is really having on the use of chemotherapy and its associated costs and outcomes for real-world breast cancer patients. (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA, Johns Hopkins / 05.06.2015

MedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John HopkinsMedicalResearch.com Interview with: Timothy Michael Pawlik, M.D., M.P.H., Ph.D. Chief, Division of Surgical Oncology Professor of Surgery John Hopkins Medical Research: What is the background for this study? Dr. Pawlik: The prognosis of patients operated on for colorectal liver metastasis (CRLM) is currently defined by various “traditional” clinicopathologic factors. However the insight that they provide is incomplete. KRAS is the most common oncogene of the RAS family and is reported in up to 30 to 40% of patients with colorectal liver metastasis. As a result, KRAS mutational status  recently attracted a lot of attention as a potential prognostic factor in colorectal liver metastasis. However, overall mutant KRAS status (compared to wild type) correlated with worse survival only in some studies. We hypothesized that the specific KRAS activating mutations (codon 12 and codon 13) confer different biologic behaviors to the tumor and in turn, account for different (if any) prognostic values. The different proportions of each KRAS specific mutation could determine whether the overall mutational status would be associated with worse survival. In our view, the different proportions of specific mutations in various cohorts could account for the variability of the outcomes in different studies. Medical Research: What are the main findings? Dr. Pawlik: Our results showed that only codon 12 KRAS mutations conferred a worse prognosis whereas codon 13 ones did not. Furthermore, we examined the different point mutations that constitute codon 12 mutations and we found that among G12A, G12D, G12V, G12C and G12S KRAS point mutations, only G12V and G12S were independent prognostic factors of worse survival. That confirmed our hypothesis that only some of the point mutations do have a significant prognostic role and that the relative incidence of those mutations could determine if overall KRAS mutational status would be associated with worse survival in a certain cohort. (more…)
Author Interviews, Fertility, Genetic Research, NEJM, University of Pittsburgh / 04.06.2015

Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213MedicalResearch.com Interview with: Alexander N Yatsenko, MD, PhD Assistant Professor, Department of OBGYN and Reproductive Science, Magee-Womens Research Institute, University of Pittsburgh, PA Pittsburgh, PA 15213 Medical Research: What is the background for this study? What are the main findings? Dr. Yatsenko: The known causes of male infertility not due to physical obstruction are usually because of sex-chromosome defects, such as deletions of the Y chromosome or duplication of the entire X chromosome in Klinefelter syndrome. Eight times out of 10, conventional genetic testing doesn’t reveal a chromosomal problem and infertility is considered idiopathic. We wanted to try to find other genetic reasons for the problem. We found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest, meaning the precursor cells could not properly undergo meiosis. We also found similar TEX11 gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic azoospermia in Pittsburgh or at a Poland infertility clinic, and in five out of 240 infertile men assessed at a collaborating Andrology clinic in Muenster, Germany. These genetic findings were confirmed on protein level using patients’ testis biopsies. (more…)
ASCO, Author Interviews, Cancer Research, Chemotherapy, Genetic Research / 03.06.2015

MedicalResearch.com spoke with Dr. Jonathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago. Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training.MedicalResearch.com spoke with Dr. Johnathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago. Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training. MedicalResearch.com: Can you tell us a little more about your background? How did you come to work at Myriad? Dr. Lancaster: My background and interests lie at the intersection of patient care and the molecular and genetic understanding of cancer. I completed my MD and Ph.D. in molecular genetics at the University of Wales, and then came to Duke for a research fellowship and residency training in Obstetrics & Gynecology. I spent twelve years as a gynecology-oncology surgeon. At the Moffitt Cancer Center, I ran a research lab attempting to understand the molecular and genetic underpinnings of ovarian cancer development and progression. Our translation research attempted to identify markers, or microRNAs, that help predict ovarian tumors’ response to chemotherapeutic agents. I also have experience in the management and financial issues facing medicine and health care. While at Moffitt, I was president of the 350-member Moffitt Medical Group, deputy physician-in-chief and director of the Center for Women's Oncology. The opportunity at Myriad Genetics allows me to utilize my experience in all three interests, clinical care, research and management, to contribute to a broader mission of cancer treatment and prevention. MedicalResearch.com: What studies are being presented at ASCO this year by Myriad associated researchers? Dr. Lancaster: There are 19 abstracts presented by Myriad at ASCO 2015, which is a testament to the emphasis Myriad places on basic and translational research (Myriad reinvests $300-400 of the proceeds from every clinical test performed into research). The studies center around two main themes: 1: An enhanced panel of genes, called MyRisk, to test for increased risk of hereditary cancers. 2: The use of Homologous Recombination Deficiency (HRD) testing and score, called MyChoice, which helps clinicians determine which patients may respond best to some chemotherapeutic agents. MedicalResearch.com: What does the MyRisk panel offer over and above the information learned from BRAC1/2 testing? Why should a patient or clinician want this testing performed? Dr. Lancaster: The MyRisk panel tests for 25 state-of-the-art genes with the goal of determining who may be at increased risk for certain malignancies even if they are BRAC1/2 negative. The typical patient is one who has a family history of cancer but may have been told she doesn’t have the ‘breast cancer gene’ because she is BRAC1/2 negative. We now know that up to 50% of these patients may carry other genes that make them more susceptible to cancer. Panel testing allows clinicians to identify many more patients at risk for cancer who would have been missed with more traditional BRAC1/2 testing alone. (more…)
Author Interviews, Diabetes, Genetic Research, Lipids, PLoS / 31.05.2015

Dr. Yann C Klimentidis, PhD Assistant professor of Epidemiology and Biostatistics Mel and Enid Zuckerman College of Public Health University of Arizona Medical CenterMedicalResearch.com Interview with: Yann Klimentidis Ph.D. Assistant Professor Mel and Enid Zuckerman College of Public Health University of Arizona Medical Research: What is the background for this study? What are the main findings? Dr. Klimentidis: Previous studies have hinted at the possibility that genes which are associated with higher triglyceride levels may also be associated with lower type-2 diabetes. We set out  to test this hypothesis in multiple prospective cohort studies, in European-Americans and in African-Americans. We found that on a collective basis, the alleles which are associated with higher triglycerides are also associated with reduced type-2 diabetes risk. We also identified some individual genetic variants which are driving this trend. (more…)
Author Interviews, Genetic Research, JAMA / 26.05.2015

Prof. Alexandre Reymond Director, Center for Integrative Genomics University of Lausanne Lausanne SwitzerlandMedicalResearch.com Interview with : Prof. Alexandre Reymond Director, Center for Integrative Genomics University of Lausanne Lausanne Switzerland MedicalResearch : What is the background for this study? Prof. Reymond: Though a subset of recurrent DNA copy number variants (differing numbers of copies of genetic sequence at locations in the genome; CNVs) with rare population prevalence are known to have strong impact on carrier’s health, up to now their association with phenotypes such as intellectual disability has been almost exclusively evaluated in clinical context using individuals ascertained for diagnostics of developmental disorders. Thus the contribution of these genetic variants to health, cognition and life quality in the general population remains unclear. We used a population biobank, that of Estonia (Estonian Genome Center, University of Tartu), which contains samples from 52,000 adult participants (representative 5% of the country’s adult population), a British birth cohort (The Avon Longitudinal Study of Parents and Children; ALSPAC) and two more population-based cohorts from the USA and Italy to explore the consequences of CNVs in presumptively healthy populations. MedicalResearch : What are the main findings? Prof. Reymond: Rare recurrent CNVs known to be causative for specific syndromes (termed genomic disorders) have a global population prevalence of around 1%. Contrary to popular assumption that carriers of these syndromic CNVs identified in unselected, but assumed to be healthy, adult population cohorts are asymptomatic, we found that they are associated with unrecognized, but serious clinical sequelae. Additionally our results showed that individually rare (less than 1 in 2000 individuals) but collectively common (around 10% of population) intermediate-size CNVs are negatively associated with carriers’ educational attainment. Altogether our results suggest that the life quality of at least 1 of 40 people might be negatively affected by rare CNVs. (more…)
Author Interviews, Diabetes, Genetic Research, Weight Research / 22.05.2015

MedicalResearch.com interview Dorota Kaminska, MSc Department of Clinical Nutrition University of Eastern Finland MedicalResearch: What is the background for this study? What are the main findings? Response: The prevalence of obesity is increasing worldwide, making it one of the biggest health problems currently facing both developed and developing countries. Obesity is considered a primary risk factor for developing type 2 diabetes. While the majority of people with type 2 diabetes are obese, most of obese people do not develop diabetes, indicating that obesity is not the only risk factor for type 2 diabetes. Both obesity and type 2 diabetes are multifactorial complex diseases that are caused by a combination of genetic, environmental, and lifestyle factors. Results from twin studies suggest that genetic factors explain 50% to 90% of the variance in body mass index (BMI) and from 45% to 85% of the diabetes risk. However genetic variations identified by genome wide association studies (GWAS) explain only 2-4% of the obesity risk and 5-10% of the type 2 diabetes risk. Several options have been debated to be a source of so called “missing heritability”, including, among others, structural DNA variations, gene-gene and gene-environment interactions, epigenetic modifications and RNA splicing. We used adipose tissue samples from Kuopio Obesity Surgery (KOBS), very low calorie diet (VLCD), Metabolic Syndrome in Men (METSIM) and European Network on Functional Genomics of Type 2 Diabetes (EUGENE2) studies to determine alternative splicing pattern of selected genes. The study focused on determining the effects of obesity and weight loss on alternative splicing of metabolically active genes (TCF7L2 and INSR). We showed that alternative splicing of both genes is dysregulated in obesity and type 2 diabetes, resulting in impaired insulin action in adipose tissue. Additionally we demonstrated, that obesity induced changes in splicing can be reversed by weight loss induced by gastric bypass surgery or very low calorie diet. Furthermore, the study identified alternatively spliced genes in the genomic regions associated with obesity risk, demonstrating that splicing of the MSH5 gene in subcutaneous fat is regulated by weight loss. The study also found that body mass index is a main determinant of TRA2B, BAG6 and MSH5 splicing in subcutaneous fat; however, the functional consequences of this finding require further investigation. These findings imply that the obesity-associated gene variants might act through regulation of splicing which in turn might underlie the pathogenesis of obesity in individuals carrying the risk variants. (more…)
Author Interviews, Genetic Research, Psychological Science / 20.05.2015

Wendong Li, Ph.D. Assistant professor of psychological sciences Department of Psychological Sciences Kansas State University Manhattan, KSMedicalResearch.com Interview with: Wendong Li, Ph.D. Assistant professor of psychological sciences Department of Psychological Sciences Kansas State University Manhattan, KS Medical Research: What is the background for this study? What are the main findings? Dr. Wen-Dong Li: There has been a "nature versus nurture" debate in leadership: Are leaders born or made? In academia, research on trait theories of leadership has shown that important individual characteristics such as personality traits are predictive of whether one is a leader or not (leadership role occupancy or emergence). One author of this paper, Dr. Arvey conducted twin studies showing that about 30% of the individual differences in leadership is attributable to individual differences in their genetic makeup. But so far, little research has examined whether specific genes are involved and no research has examined the pathways linking genes to leadership. This is where this research came in. We found that a dopamine transporter gene, DAT1 was involved in genetic influences on leadership role occupancy, but through two opposing pathways. One pathway is through proactive personality: DAT1 10-repeat allele was negatively related to proactive personality, which in turn was positively associated with leadership role occupancy. The negative indirect effect was significant. On the other hand, DAT1 was positively related to (moderate) rule breaking, which was positively associated with leadership role occupancy. The overall relationship between DAT1 and leadership was not significant. Thus we call it a mixed blessing because the two opposing mechanisms offset each other. (more…)