Serotonin Receptors Tied To Weight Gain From Atypical Antipsychotic Medications

MedicalResearch.com Interview with:

Chen Liu, Ph.D. Assistant Professor Departments of Internal Medicine and Neuroscience Division of Hypothalamic Research The University of Texas Southwestern Medical Center Dallas, Texas 75390-9077

Dr. Chen Liu

Chen Liu, Ph.D.
Assistant Professor
Departments of Internal Medicine and Neuroscience
Division of Hypothalamic Research
The University of Texas Southwestern Medical Center
Dallas, Texas 75390-9077 

MedicalResearch.com: What is the background for this study?

Response: Atypical antipsychotics are second-generation antipsychotics (SGAs) that have been increasingly used to treat a variety of neuropsychiatric conditions such as schizophrenia, depression, and autism. Many patients taking these medications, however, are left in an agonizing dilemma.

On one hand, they rely on these drugs’ psychotropic effect for normal functioning in daily life. On the other, many SGAs, including the most widely prescribed olanzapine and clozapine, can cause a metabolic syndrome that is known for excessive weight gain, dyslipidemia, and type-2 diabetes_ENREF_2. Notably, while full-blown type 2 diabetes and morbid obesity typically take years to unfold in the general population, these conditions progress at a much faster pace (within months) following second-generation antipsychotics treatment. Other factors such as ethnicity, age, and sex can also aggravate SGA-induced metabolic syndrome. Together, these peculiar features strongly suggest a distinct etiology underlying SGA-induced metabolic syndrome that has yet been fully elucidated. Currently, there is no medication specifically targeting SGA-induced metabolic syndrome. For many youths and adults taking second-generation antipsychotics, metabolic complications are difficult to manage as lifestyle changes, nutritional consulting, and commonly used anti-diabetic medications only provide limited relief.

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Holes in Cigarette Filters Linked To Increase in Lung Adenocarcinomas

MedicalResearch.com Interview with:
Peter G. Shields, M.D.
Deputy Director, Comprehensive Cancer Center
James Cancer Hospital
Professor, College of Medicine
Julius F. Stone Chair in Cancer Research
The Ohio State University Columbus, OH

MedicalResearch.com: What do we know about the health effects of cigarette filters? 
Response:  The issue is that the design of the filters makes a cigarette even more dangerous, which can be regulated by the FDA. The issue is not about having a filter, but how they are made. And now we are changing the dialogue to the design of virtually all cigarettes. The holes on the filter are likely one reason the cigarettes of today are more dangerous.

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NSAIDS May Increase Mortality From Endometrial Cancer

MedicalResearch.com Interview with:

Theodore Brasky, PhD Research Assistant Professor Center of Excellence in Regulatory Tobacco Science Epidemiology College of Public Health The Ohio State University

Dr. Theodore Brasky

Theodore Brasky, PhD
The Ohio State University
Comprehensive Cancer Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is a significant amount of data to suggest that long-term, regular use of nonsteroidal anti-inflammatory drugs (NSAIDS; examples include aspirin and ibuprofen) are associated with reduced risks of several cancers. Although the data across studies are inconsistent, one such candidate is endometrial cancer, which is the most common gynecologic cancer. There is good evidence that the use of these medications is associated with improved prognosis among patients diagnosed with colon cancer. Despite the importance of inflammation in endometrial cancer progression, very few have examined whether use of NSAIDs is associated with risk of death or recurrence from the disease. The study we published is the first of its kind to examine NSAID use comprehensively and in a study of over 4,000 patients.

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Study Links Well-Water Arsenic To Increased Bladder Cancer Risk in New England

MedicalResearch.com Interview with:

Dr. Debra Silverman Sc.D Branch Chief and Senior Investigator in the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics National Cancer Institute

Dr. Debra Silverman

Dr. Debra Silverman Sc.D
Branch Chief and Senior Investigator in the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics
National Cancer Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Silverman: We know that bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence patterns in Maine, New Hampshire and Vermont are similar—about 20% higher than those for the United States overall. Elevated rates have been observed in both men and women, suggesting the role of a shared environmental etiologic factor.

A unique feature of northern New England is that a high proportion of the population uses private wells as their primary source of drinking water. The well water may contain low-to-moderate levels of arsenic. There are two possible sources of this arsenic contamination:

  • Naturally occurring arsenic from geological sources (released from rock deep in the earth)
  • Leaching of arsenic-based pesticides used on food crops many years ago. From the 1920s through the 1960s there was extensive agricultural use of arsenic-based pesticides. These compounds were used on food crops such as blueberries, apples and potatoes. Residue from the treatments may have leached into the ground water.

Intake of water containing high levels of arsenic is an established cause of bladder cancer, largely based on studies conducted in highly exposed populations. However, emerging evidence suggests that low-to-moderate levels of exposure may also increase bladder cancer risk.

To explore possible reasons for the excess incidence of bladder cancer in northern New England, we conducted a large, comprehensive population-based case-control study in Maine, New Hampshire and Vermont. We examined the role of known and suspected bladder cancer risk factors, with a focus on private well water consumption and arsenic levels in drinking water.

The major cause of bladder cancer is cigarette smoking. Some occupational exposures (e.g., exposure to metalworking fluids such as that experienced by metalworkers and some types of machine operators) are also associated with elevated risk. However, smoking and occupational exposures do not appear to explain the New England bladder cancer excess.

This study was funded and carried out by researchers in the NCI Division of Cancer Epidemiology and Genetics in collaboration with the Geisel School of Medicine at Dartmouth, the Departments of Health for Maine, New Hampshire, and Vermont, and the US Geological Survey.

We reported that heavy consumption of drinking water from private dug wells (which are shallow—less than 50 feet deep—and susceptible to contamination from manmade sources than drilled wells), established prior to 1960 (when arsenic-based pesticides were widely used), may have contributed to the longstanding bladder cancer excess in northern New England.

We saw that cumulative arsenic exposure from all water sources showed an increasing risk with increasing exposure (exposure-response relationship). Among the highest exposed participants, risk was twice that of the lowest exposure group. (Cumulative arsenic exposure is a measure of the average daily arsenic intake by number of days of arsenic exposure.)

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Hepatitis C Raises Risk of HPV Head and Neck Cancers

MedicalResearch.com Interview with:

Harrys A. Torres, MD, FACP, FIDSA Associate Professor Director of Hepatitis C Clinic Department of Infectious Diseases, Infection Control and Employee Health The University of Texas MD Anderson Cancer Center Houston TX 77030

Dr. Harrys Torres

Harrys A. Torres, MD, FACP, FIDSA
Associate Professor
Director of Hepatitis C Clinic
Department of Infectious Diseases, Infection Control and Employee Health
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. Torres: Hepatitis C virus (HCV) is an oncogenic virus and is associated with an increased risk of liver cancer and certain types of non-Hodgkin lymphomas. In 2009, at MD Anderson Cancer Center, we set up the first clinic in the United States, and probably in the world, specifically devoted to managing HCV infection in cancer patients. In the clinic, we expected to see a number of patients with liver cancers and non-Hodgkin’s lymphoma, as these have documented associations with HCV. Unexpectedly, we saw a high number of HCV-infected patients with head and neck cancers, and wondered whether there was an undiscovered association between having the infection and head and neck cancers. To explore this, we conducted a case-control study using 409 head and neck cancer subjects (164 oropharyngeal, 245 non-oropharyngeal [oral cavity, nasopharynx, larynx] cancers) and 694 control subjects with other smoking-associated cancers (378 lung, 168 esophagus, and 148 urinary bladder cancers), and compared the prevalence of HCV infection in the two groups. We observed a high prevalence of HCV infection in oropharyngeal (14%) and non-oropharyngeal (20%) cancer patients when compared to control subjects (6.5%). After adjusting for confounders such as smoking, alcohol intake, and socioeconomic status, HCV-infected individuals were 2.04 times more likely to have oropharyngeal cancers and 2.85 times more likely to have non-oropharyngeal cancers. Of note, HCV was associated only with patients with oropharyngeal cancers that tested positive for human papilloma virus, which is one of the main virus linked with increased risk of oropharyngeal cancers.

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Early Breast Cancer Screening Recommended For Survivors of Childhood Hodgkin’s Lymphoma

MedicalResearch.com Interview with:

David Hodgson, MD, MPH, FRCPC Associate Professor University of Toronto

Dr. David Hodgson

David Hodgson, MD, MPH, FRCPC
Associate Professor
University of Toronto
Toronto, ON Canada  

MedicalResearch.com: What is the background for this study?

Dr. Hodgson: We know that treatment for childhood Hodgkin lymphoma can cause some side effects that arise years after treatment is  finished. In particular, radiotherapy given to the chest of adolescent females increases the risk of developing breast cancer in young adult survivors. But there are very little data about whether the early initiation of breast cancer screening will prevent breast cancer deaths in these survivors, and what kinds of screening is optimal. This is important because less than half of these young survivors are undergoing breast cancer screening, and in some jurisdictions early screening is not covered by insurance.

MedicalResearch.com: What are the main findings?

Dr. Hodgson: Because there has not been, and likely never will be, a large randomized screening trial for these patients, we used all the available information about their breast cancer risk, other health issues and the effectiveness of screening, and created a mathematical model that allows us to estimate the number of breast cancer deaths prevented by starting screening at age 25 for women who had received chest RT as teenagers. We found that one would have to invite about 260 survivors to early mammographic screening to prevent one breast cancer death, which compares favorably to other accepted reasons for breast cancer screening. Using MRI for screening, approximately 80 women would have to be invited to prevent one breast cancer death, because MRI is so much more sensitive than mammography. One of the problems with MRI, however, is that a substantial number of women will have “false positive” tests – abnormal findings that are not really cancer.

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Genetics Study Points To Different Pathways For Melanoma Risk

MedicalResearch.com Interview with:

Nancy E. Thomas, MD PhD Department of Dermatology, University of North Carolina Chapel Hill, NC 27599

Dr. Nancy E. Thomas

Nancy E. Thomas, MD PhD
Department of Dermatology, University of North Carolina
Chapel Hill, NC 27599

Medical Research: What is the background for this study?

Dr. Thomas: Melanoma had been thought for some time to arise from at least two causal pathways, a ‘chronic sun exposure pathway’ and a ‘nevus pathway’. However, the role of inherited genetic variation in development of melanoma along these pathways had not previously been studied. Thus, we chose to examine the association of SNPs in putative low-penetrance melanoma susceptibility loci with histologic markers of divergent pathways.

Medical Research: What are the main findings?

Dr. Thomas: Within the large Genes, Environment and Melanoma Study, we investigated the relationship of germline variants in newly identified low-penetrance melanoma risk loci to histologic markers of divergent causal pathways in melanoma. We present strong evidence that the IRF4 rs12203592*T genotype is positively associated with chronic sun exposure-related melanoma and inversely associated with nevus-related melanoma. We also found that the IRF4 rs12203592 genotype is linked to the bi-model age distribution known to occur in melanoma and which is related to the divergent pathways. IRF4 rs12203592 is a functional variant known to affect IRF4 expression in human skin and melanoma cell lines. We conclude that IRF4rs12203592 is likely, at least in part, to determine pathway-specific risk for melanoma development.

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No Increase Risk of Breast Cancer Recurrence With Antidepressants While On Tamoxifen

Reina Haque, PhD, MPH Research scientist Department of Research & Evaluation Kaiser Permanente Southern California Pasadena Calif

Dr. Haque

MedicalResearch.com Interview with:
Reina Haque, PhD, MPH

Research scientist
Department of Research & Evaluation
Kaiser Permanente Southern California
Pasadena Calif

Medical Research: What is the background for this study? What are the main findings?

Dr. Haque: Tamoxifen is a commonly prescribed generic drug taken by women with breast cancer to reduce their chances of developing a recurrence. Tamoxifen is recommended for five years, but has notable side effects, including hot flashes, night sweats and depression. Since hormone replacement therapy is not recommended to alleviate these symptoms in breast-cancer survivors, antidepressants have been increasingly prescribed for relief. Almost half of the 2.4 million breast-cancer survivors in the U.S. take antidepressants.

However, previous studies have suggested that antidepressants reduce tamoxifen’s effectiveness in lowering subsequent breast-cancer risk. This study was conducted to determine whether taking tamoxifen and antidepressants (in particular, paroxetine) concomitantly is associated with an increased risk of recurrence or contralateral breast cancer.
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Young Black Colon Cancer Patients Have Greater Risk of Recurrence

Harry H. Yoon, MD Mayo Clinic Rochester, MN 55905MedicalResearch.com Interview with:
Harry H. Yoon, MD
Mayo Clinic
Rochester, MN 55905

Medical Research: What is the background for this study? What are the main findings?

Dr. Yoon: In the U.S., the survival of patients with colon cancer is known to differ by race, with individuals of black race having worse outcomes than those of white race.

However, it has been difficult to tease apart why the differences in survival exist.

It is generally believed that social or other non-biologic factors (eg, decreased access to care, suboptimal treatment) contribute to the discrepancy.  It’s also known that differences in the general medical condition of patients could affect how long a patient lives.

However, it is unknown whether there are race-based differences in the biology of colon tumors themselves.  This biology can be reflected in the genetic composition of tumors, as well as by whether and how quickly the cancer returns after the patient has undergone surgery and chemotherapy.

In addition, it is unknown whether race-based differences in biology may be related to the age of the patient at the time of diagnosis.  Blacks with colorectal cancer typically have an earlier age of onset than whites do.

A major barrier to addressing these questions are that there are very few large populations of colon cancer patients where everyone had the same disease stage and received uniform treatment, and where patients were monitored for years afterward specifically to see whether the cancer returned.  It is much harder to measure whether cancer has returned (ie, cancer recurrence), as compared to simply knowing whether a patient is alive or dead.  This difference is important, because knowing about cancer recurrence sheds more light on cancer biology than only knowing about patient survival, since many factors unrelated to cancer biology (eg., heart disease) can affect whether a person is alive or dead.

The most reliable data on cancer recurrence (not just patient survival) generally comes from patients who have enrolled in a clinical trial.  In the Alliance N0147 trial, all patients had the same cancer stage (ie, stage III), underwent surgery and received standard of care chemotherapy (ie, “FOLFOX”) after surgery.  Patients had uniform, periodic monitoring after chemotherapy to see if the cancer returned.

In other words, examining racial outcomes in this cohort largely eliminates some of the key factors (eg, decreased access to care, suboptimal treatment) that are believed to contribute to racial discrepancies, and provides a unique opportunity to determine if differences in cancer biology between races may exist.

This study was done to see if colon cancers are genetically different based on race, and whether race-based differences exist in cancer recurrence rates.

The study found that tumors from whites, blacks, and Asians were different in terms of the frequency of mutations in two key cancer-related genes, BRAF and KRAS.  Tumors from whites were twice as likely to have mutated BRAF (14% in whites compared to 6% in Asians and 6% in blacks).  Tumors from blacks had the highest frequency of KRAS mutations (44% in blacks compared to 28% in Asians and 35% in whites).  Tumors from Asians were the mostly likely to have normal copies of both genes (67% in Asians compared to 50% in blacks and 51% in whites).

Next, the study found that the colon cancers among blacks had more than double the risk of cancer recurrence, compared to whites.  However, this discrepancy was only evident among young patients (ie, aged less than 50 years).  Almost 50% of younger black patients experienced colon cancer recurrence within 5 years, compared to ~30% of black patients over age 50, or compared to white or Asian patients regardless of age. The worse outcome among young blacks remained evident even after adjusting for many potential confounding factors, such as tumor grade, the number of malignant nodes, or the presence of BRAF or KRASmutations.  Because this question was examined in a clinical trial cohort of uniform stage and treatment, the role of multiple important potential confounders was diminished.

To our knowledge, this is the first report indicating that colon cancers from young black individuals have a higher chance of relapsing after surgery and chemotherapy, compared to those from white individuals.

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Breast Cancer Pattern Likely To Change as Population Ages

Philip S. Rosenberg, PhD Biostatistics Branch, Senior Investigator Division of Cancer Epidemiology and Genetics National Cancer Institute, 9609 Medical Center Drive Bethesda, MD 20892MedicalResearch.com Interview with:
Philip S. Rosenberg, PhD
Biostatistics Branch, Senior Investigator
Division of Cancer Epidemiology and Genetics
National Cancer Institute, 9609 Medical Center Drive
Bethesda, MD 20892 

Medical Research: What is the background for this study? What are the main findings?

Dr. Rosenberg: It has been previously reported that breast cancer burden (number of new cases diagnosed in a year) is expected to rise in the future, mostly due to the aging of the female population in the US.

Also, it has been established that the age-adjusted breast cancer incidence rates (cases per 100,000 women per year) are increasing for invasive ER-positive cancers overall and decreasing for ER-negative cancers overall. When taken together, these two trends tend balance each other out, resulting in a somewhat flat breast cancer incidence rate overall. 

Though the overall trends for invasive breast cancer have been previously reported, this study uses a more refined forecasting method by including recent birth cohort patterns to forecast breast cancer to 2030 by age group, estrogen receptor-status, and invasive vs. in situ tumors.

New in this report are the findings for in situ tumors and the more granular break down by age, ER status, and invasive vs. in situ tumors both for rate and burden (number of cases).
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