Author Interviews, Breast Cancer, Genetic Research, Ovarian Cancer / 26.05.2016
Breast and Ovarian Cancers May Have Common Epigenetic Origin
MedicalResearch.com Interview with:
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Dr. Sibaji Sarkar[/caption]
Sibaji Sarkar Ph.D
Instructor of medicine
Boston University School of Medicine
Boston
MedicalResearch.com: 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.
Dr. Sibaji Sarkar[/caption]
Sibaji Sarkar Ph.D
Instructor of medicine
Boston University School of Medicine
Boston
MedicalResearch.com: 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.
Dr. Ingrid Elisabeth-Christophersen[/caption]
Ingrid Elisabeth Christophersen MD PhD
Postdoctoral research fellow
Cardiovascular Research Center (CVRC)
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Christophersen: Several recent studies have utilized the CHA2DS2-VASc risk score to predict risk of atrial fibrillation (AF). However, the CHA2DS2-VASc was developed for prediction of stroke risk in patients with AF and has not been validated for prediction of AF risk. We have evaluated how well the CHA2DS2-VASc performed at predicting risk of AF compared with the most validated clinical risk score for AF - the CHARGE-AF risk score - in the Framingham Heart Study. We showed that the CHARGE-AF risk score performed better at predicting risk of AF than the CHA2DS2-VASc.
Nana Keum[/caption]
NaNa Keum, ScD|
Harvard T. H. Chan
School of Public Health Department of Nutrition
Departments of Nutrition and Epidemiology,
Harvard T.H. Chan School of Public Health
Boston, MA 02115
MedicalResearch.com: What is the background for this study?
Response: While general health benefits of physical activity are well-known, evidence on its specific benefits on cancer endpoints is limited and physical activity guidelines for cancer prevention lack details in terms of the optimal dose, type and intensity of physical activity.
MedicalResearch.com: What are the main findings?
Response: We found that the optimal exercise regime to prevent overall digestive system cancers may be to accumulate 30 MET-hours/week of physical activity primarily through aerobic exercise and regardless of its intensity.
Dr. Jennifer Kuk[/caption]
Jennifer L. Kuk, PhD
Associate Professor
York University
School of Kinesiology and Health Science
Toronto, Ontario
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kuk: Artificial sweeteners are used to help individuals manage their weight, however, individuals who consume aspartame (a type of artificial sweeteners) have worse glucose metabolism than individuals with the same body weight but do not consume aspartame. This observation was only true for adults with obesity. Further, saccharin and natural sugars were not associated with differences in health after considering differences in obesity.
Dr. Prateek Sharma[/caption]
Dr. Prateek Sharma MD
Professor, Gastroenterology, Hepatology and Motility
Kansas University Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sharma: Reflux symptoms are a risk factor for Barrett's esophagus and approximately 10-15% of patients with reflux are diagnosed with Barrett's esophagus. Barrett's esophagus is a risk factor for esophageal adenocarcinoma. We evaluated the trends in the prevalence of be in patients with reflux disease over years and found that the prevalence of be was decreasing.
Dr. Bo Qin[/caption]
Bo (Bonnie) Qin, Ph.D.
Postdoctoral Scholar
Rutgers Cancer Institute of New Jersey
New Brunswick, NJ 08903
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Qin: Preventing or delaying the age-related cognitive decline that typically precedes the onset of dementia is particularly important considering that no effective strategies for dementia treatment have been identified. Vascular conditions such as hypertension are thought to be risk factors for cognitive decline, but important gaps in the literature on this topic remain.
Randomized clinical trials of blood pressure-lowering treatments for reducing the risk of cognitive decline or dementia have largely failed to achieve beneficial effects. However, over the past 6 years, scientific evidence has accumulated that blood pressure variability over monthly or yearly visits may lead to greater risk of stroke and small and larger vessel cerebrovascular diseases. They could lead to subsequent changes related to cognitive dysfunction among older adults. We, therefore, hypothesized that blood pressure variability between visits is associated with a faster rate of cognitive function among older adults.
Dr. Alan Brown[/caption]
Alan S. Brown, M.D., M.P.H.
Professor of Psychiatry and Epidemiology
Columbia University Medical Center
Director, Program in Birth Cohort Studies, Division of Epidemiology
New York State Psychiatric Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Brown: Smoking during pregnancy is a risk factor for several pregnancy-related outcomes including low birthweight and preterm birth. Evidence for a link with schizophrenia is scant. We analyzed a maternal biomarker of smoking called cotinine, a nicotine metabolite, in mothers of nearly 1,000 schizophrenia cases and 1,000 controls in a national birth cohort in Finland. We found that heavy smoking in pregnancy was related to a 38% increase in schizophrenia risk in offspring and that as cotinine levels increased even in the more moderate smokers risk of schizophrenia also increased.
Dr. Jiang He[/caption]
Jiang He, M.D., Ph.D.
Joseph S. Copes Chair and Professor
Department of Epidemiology
School of Public Health and Tropical Medicine
Tulane University, New Orleans
MedicalResearch: What is the background for this study?
Dr. Jiang He: Chronic kidney disease is associated with increased risk of end-stage renal disease, cardiovascular disease, and all-cause mortality. A positive association between sodium intake and blood pressure is well established in observational studies and clinical trials. However, the association between sodium intake and clinical cardiovascular disease remains less clear. Positive monotonic, J-shaped, and U-shaped associations have been reported. Methodologic limitations, including inconsistencies in dietary sodium measurement methods, could be contributing to these conflicting findings. Furthermore, no previous studies have examined the association between sodium intake and incident cardiovascular disease among patients with chronic kidney disease.
Dr. Brian Stansfield[/caption]
Dr. Brian Stansfield MD
Neonatologist
Children's Hospital of Georgia and the Medical College of Georgia
Augusta University
MedicalResearch.com: What is the background for this study?
Dr. Stansfield: Since the mid-20th century, we have experimental evidence in animal models and human data demonstrating the influence of maternal nutrition on the offspring - both in the short term and long term. Low birth weight has been connected with higher incidence of cardiometabolic diseases including insulin resistance, coronary artery disease, and hypertension. Interestingly, low birth weight infants grow up to be relatively thin adults compared to their normal or high birth weight counterparts. Conversely, high birth weight infants tend to become heavier adults and obesity is directly linked with the same adult outcomes. So the association of cardiac and metabolic diseases with low birth weight is not linked to adult obesity in general. Thus, speculation as to why extremes of birth weight lead to adult onset cardiometabolic disease suggests different mechanisms and modifying factors.
MedicalResearch.com: What are the main findings?
Dr. Stansfield: The findings of our study shed considerable light on the relationship between birth weight and risk factors for insulin resistance and visceral adiposity. Using magnetic resonance imaging (MRI) to achieve precise measurements of visceral adipose content and biomarkers for insulin resistance, we show that both low and high birth weight are associated with increased visceral adiposity and insulin resistance in a healthy population of adolescents aged 13-17 years. This association persists when we account for several recognized confounders including age, sex, race, activity level, and socioeconomic status. The most interesting finding of our study is that when you account for each adolescent’s current body mass index, a measure of obesity, the relationship between increased visceral fat and insulin resistance and low birth weight is strengthened suggesting that these adolescents had relatively high visceral adipose content despite obesity rates that were similar to their normal birth weight counterparts. On the other hand, correction for adolescent BMI (obesity) reduced the relationship between these metabolic markers and high birth weight infants. Thus, low birth weight infants may develop insulin resistance and increased visceral fat, both significant risk factors for cardiovascular disease and metabolic disease, despite having a relatively normal body shape in adolescents.
Dr. Sikarin Upala[/caption]
Sikarin Upala MD, MS, LLB
Internal Medicine, Bassett Medical Center and Columbia University College of Physicians and Surgeons, Cooperstown, New York
Preventive and Social Medicine
Mahidol University, Bangkok, Thailand
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Upala: Chronic hepatitis C virus infection is the most common cause of chronic liver disease and cirrhosis as well as the most common cause of liver transplantation in the United States. As caffeine has been found to be related to decreased liver enzymes, chronic liver disease,cirrhosis, and risk of hepatocellular carcinoma in several liver disease pathologies. There is inconclusive findings on the effect of caffeine on hepatitis C infected patients. Thus, we conducted a systematic review and meta-analysis to summarize the effect of caffeine consumption in patients with chronic hepatitis C.
We found that caffeine consumers have a 61% reduced risk of developing advanced hepatic fibrosis, which is one of the consequence of chronic hepatitis C. Our meta-analysis result is in the same way with other studies who found that coffee consumption could prevent the development of hepatic fibrosis in patients with liver disease. However, we cannot conclude about the effect of caffeine on HCV viral load as there is not enough information.
Dr. Deborah Cohen[/caption]
Deborah A. Cohen, MD, MPH
RAND Corporation
Santa Monica, CA 90407
MedicalResearch.com: What is the background for this study?
Dr. Cohen: An extensive infrastructure of neighborhood parks supports leisure time physical activity in most U.S. cities; yet, most Americans do not meet national guidelines for physical activity. Neighborhood parks have never been assessed nationally to identify their role in physical activity. We visited a representative sample of 174 parks in 25 cities across the United States and assessed their use as well as local park management policies.
MedicalResearch.com: What are the main findings?
Dr. Cohen: We found that nationwide, the average neighborhood park of 8.8 acres averaged 20 users/hour or an estimated 1,533 person hours of weekly use. Park use was higher in parks that were larger and had more facilities and that were in neighborhoods with a higher population density and lower percentage of households in poverty. Walking loops and gymnasia each generated 221 hours/week of moderate to vigorous physical activity. Seniors represented 4% of park users, but 20% of the general population. Programming and marketing were associated with 37% and 63% more hours of moderate to vigorous physical activity/week in parks, respectively.
The lower use of parks in low-income than in high-income neighborhoods was largely explained by fewer supervised activities and marketing/outreach efforts.
Dr. Annette Schürmann[/caption]
Prof-Dr. Annette Schürmann
Department of Experimental Diabetology
German Institute of Human Nutrition Potsdam-Rehbruecke
Nuthetal, Germany
MedicalResearch.com: 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.
Dr. James Kirkpatrick[/caption]
James N. Kirkpatrick, MD
Director of the Echocardiography Laboratory
Division of Cardiology
Ethics Consultation Service
University of Washington, Seattle
MedicalResearch.com: What is the background for this study?
Dr. Kirkpatrick: With significant advances in technology, implanted cardiac devices like pacemakers and defibrillators, replacement heart valves, and mechanical pumps which assist or replace the pumping function of the heart have become standard therapies for patients with severe cardiac disease. Many patients who would previously have died after living with severe symptoms live longer and with improved quality of life. This is particularly true for elderly patients who receive transcatheter aortic valve replacement (TAVR—valve replacement that doesn’t require open heart surgery) and ventricular assist device (VAD—a durable mechanical heart pump) implantation.
However, like everyone, these patients will die, and some of the patients will experience device complications which will shorten their lives. Elderly patients, in particular, are at risk for device complications, high symptom burden, and loss of the ability to make healthcare decisions, due to illnesses like strokes or dementia. Symptom management and advance care planning are the hallmarks of the medical specialty of Palliative Care and are particularly important in patients with TAVR and VADs, yet patients and clinicians don’t often think of Palliative Care when considering high tech, life-prolonging therapies. The Palliative Care Working Group of the American College of Cardiology’s Geriatrics Section therefore sought to gather data on the attitudes toward Palliative Care among cardiovascular clinicians and the current state of involvement of Palliative Care in the care of patients with TAVR and VAD.
Dr. Alejandro Sousa[/caption]
Alejandro Sousa, MD, PhD
Department of Urology, Comarcal Hospital
Monforte, Spain
MedicalResearch.com: What is the background for this study?
Dr. Sousa: Bladder Cancer management has remained stable over the past 25 years, with very little in the way of new therapies or approaches being developed. Traditional treatment using intravesical Mitomycin C for Non Muscle Invasive Bladder Cancer (NMIBC) patients is limited due it's low absorption levels. Device assisted therapies that deliver Chemo-hyperthermia offer a new hope, with the potential for improved outcomes and better disease management due the the increased drug activity and better efficacy. We wanted to investigate the optimal treatment regime for this new therapy and whether it provides a safe and effective alternative to current standard treatment.
Dr. James Welsh[/caption]
James S. Welsh, MS, MD, FACRO
President, American College of Radiation Oncology
Professor and Medical Director
Director of Clinical & Translational Research
Department of Radiation Oncology
Stritch School of Medicine Loyola University- Chicago
Cardinal Bernardin Cancer Center
Maywood, IL 60153
Chief of Radiation Oncology
Hines VA Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Welsh: Cancer immunotherapy could represent a truly powerful means of addressing cancer. Although immunotherapy itself is not new, there are new agents and combinations of older agents (including radiation therapy) that could prove more successful than anything we have seen in many years. The data in melanoma thus far is quite encouraging and this preliminary success could possibly extend to many other malignancies as well.
Dr. Aaron Thrift[/caption]
Aaron Peter Thrift, Ph.D
Assistant Professor
Duncan Cancer Center
Department of Medicine, Gastroenterology Section
Baylor College of Medicine
Houston, TX, US
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Thrift: Patients with Barrett’s esophagus are at significantly higher risk of developing esophageal adenocarcinoma. Due to the continued rise in incidence of esophageal adenocarcinoma attention has turned to chemoprevention as a method to delay or halt the progression of Barrett’s esophagus to neoplasia, including invasive cancer. Acid suppressive medications, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs), are commonly used in patients with gastroesophageal reflux disease (GERD), the primary risk factor for Barrett’s esophagus.
We contacted a nested case-control study involving 311 patients with Barrett’s esophagus who developed esophageal adenocarcinoma (cases) and 856 matched controls (patients with Barrett’s esophagus but who did not develop esophageal adenocarcinoma). Compared to never users, we found that Barrett’s esophagus patients taking PPIs and H2RAs had 69% and 45% lower risk of esophageal adenocarcinoma, respectively. The associations were independent of other risk factors for progression, including concomitant use of nonsteroidal anti-inflammatory drugs and statins.
Dr. Jill Cameron[/caption]
Jill Cameron, PhD
Canadian Institutes of Health Research New Investigator
Associate Professor,
Department of Occupational Science and Occupational Therapy
Rehabilitation Sciences Institute
Faculty of Medicine,
University of Toronto
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Cameron: In the world of critical illness, a lot of research has focused on helping people to survive – and now that more people are surviving, we need to ask ourselves, what does quality of life and wellbeing look like afterwards for both patients and caregivers? The aim of our research was to identify factors associated with family caregiver health and wellbeing during the first year after patients were discharged from the Intensive Care Unit. We examined factors related to the patient and their functional wellbeing, the caregiving situation including the impact it has on caregivers everyday lives, and caregiver including their sense of control over their lives and available social support. We used Pearlin’s Caregiving Stress Process model to guide this research.
From 2007-2014, caregivers of patients who received seven or more days of mechanical ventilation in an ICU across 10 Canadian university-affiliated hospitals were given self-administered questionnaires to assess caregiver and patient characteristics, caregiver depression symptoms, psychological wellbeing, and health-related quality of life. Assessments occurred seven days and three, six and 12-months after ICU discharge.
The study found that most caregivers reported high levels of depression symptoms, which commonly persisted up to one year and did not improve in some. Caregiver sense of control, impact on caregivers’ everyday lives, and social support had the largest relationships with the outcomes. Caregivers’ experienced better health outcomes when they were older, caring for a spouse, had higher income, better social support, sense of control, and caregiving had less of a negative impact on their everyday lives. No patient characteristics or indicators of illness severity were associated with caregiver outcomes.
Poor caregiver outcomes may compromise patients’ rehabilitation potential and sustainability of home care. Identifying risk factors for caregiver distress is an important first step to prevent more suffering and allow ICU survivors and caregivers to regain active and fulfilling lives.
Dr. Nicole Shen[/caption]
Dr. Nicole Shen
New York-Presbyterian/Weill Cornell Medical College
MedicalResearch.com: What is the background for this study?
Dr. Shen: Clostridium difficile infection (CDI) is a persistent, healthcare associated infection with significant morbidity and mortality that costs the US billions of dollars annually. Prevention is imperative, particularly for patients at high risk for infection – hospitalized adults taking antibiotics. Trials have suggested probiotics may be useful in preventing CDI. We conducted a systematic review with meta-analysis in this high-risk population, hospitalized adults receiving antibiotics, to evaluate the current evidence for probiotic use for prevention of CDI.
Dr. Susan McCurry[/caption]
Dr. Susan McCurry
Principal Investigator
Clinical psychologist and research professor
School of Nursing
University of Washington
MedicalResearch.com: What is the background for this study?
Dr. McCurry: Every woman goes through menopause. Most women experience nighttime hot flashes/sweats and problems sleeping at some point during the menopause transition. Poor sleep leads to daytime fatigue, negative mood, and reduced daytime productivity. When sleep problems become chronic – as they often do – there are also a host of negative physical consequences including increased risk for weight gain, diabetes, and cardiovascular disease. Many women do not want to use sleeping medications or hormonal therapies to treat their sleep problems because of concerns about side effect risks. For these reasons, having effective non-pharmacological options to offer them is important.
Prof. Luis. Rohde[/caption]
Luis Augusto Rohde MD, PhD
Full Professor
Department of Psychiatry
Federal University of Rio Grande do Sul
Director
ADHD Program
Hospital de Clínicas de Porto Alegre
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The idea that Attention-deficit/Hyperactivity Disorder always begins in childhood has been held for decades even without proper testing. The main manuals of psychiatric diagnoses require age at onset in childhood as a core feature of the disorder. In a large birth cohort followed until age 18, we identified many young adults presenting with a full impairing ADHD syndrome. They had consistently worse outcomes - criminality, substance abuse, traffic accidents, among others - than their counterparts without ADHD. However, most of these young adults (84.6%) presenting with a full impairing syndrome did not have a prior diagnosis in their childhood years. This surprising observation held after many secondary analyses exploring possible biases, like comorbidities in young adulthood, subthreshold ADHD in childhood and change of information source.
Dr. Samir Ballas[/caption]
Samir K. Ballas MD FACP
Emeritus Professor of Medicine and Pediatrics
Department of Medicine/Cardeza Foundation for Hematologic Research
Thomas Jefferson University
Philadelphia, PA
Medicalresearch.com: What is the background for this study?
Dr. Ballas: Previous studies have shown that the incidence of overt stroke is about 11% in children with sickle cell anemia by ages 2 - 20 years. Untreated stokes recur periodically with increasing severity and mortality. Transfusion therapy has been documented to decrease the frequency and morbidity of stroke in children by 90%. Accordingly, children who develop overt stroke are treated with chronic blood exchange transfusion to prevent the recurrence of additional strokes. When children reach the age of 18-20 years their medical care is transitioned to adult programs. This transition process is associated with several issues one of which is the discontinuation of chronic blood exchange transfusion in patients with history of overt stokes partly due to logistic considerations and partly due to lack of research in strokes in adult patients and the complications of chronic blood transfusion .
Medicalresearch.com: What are the main findings?
Dr. Ballas: The major finding of the study is that the discontinuation of chronic blood exchange after transition to adult programs is associated with increased mortality. All the patients who discontinued blood transfusion died within 3-5 years after transition whereas patients who continued having blood exchange transfusion survived to a mean age of 36 years at the time of writing this study.
Dr. Steven Moore[/caption]
Steven C. Moore PhD, MPH
Division of Cancer Epidemiology and Genetics
Rockville, MD
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Moore: More than half of Americans fail to meet recommended levels of regular physical activity; physical inactivity has become a major public health concern.
Physical activity during leisure time is known to reduce risks of heart-disease and all-cause mortality, as well as risks of colon, breast, and endometrial cancers. However, less is known about whether physical activity reduces risk of other cancers.
Hundreds of prospective studies have examined associations between physical activity and risk of different cancers. Due to small case numbers, results have been inconclusive for most cancer types.
In this study, we examined how leisure-time physical activity relates to risk of 26 different cancer types in a pooled analysis of 12 prospective cohort studies with 1.44 million participants. Our objectives were to identify cancers associated with leisure-time physical activity, and determine whether associations varied by body size and/or smoking history.