2.50
Hdl Handle:
http://hdl.handle.net/10755/157388
Type:
Presentation
Title:
CANDIDATE GENE APPROACH TO ENHANCE BREAST CANCER SYMPTOM MANAGEMENT
Abstract:
CANDIDATE GENE APPROACH TO ENHANCE BREAST CANCER SYMPTOM MANAGEMENT
Conference Sponsor:Western Institute of Nursing
Conference Year:2010
Author:Von Ah, Diane, PhD, RN
P.I. Institution Name:Indiana University
Title:Assistant Professor
Contact Address:1111 Middle Drive, Indianapolis, IN, 46202, USA
Co-Authors:Todd Skaar; Fredrick Unverzagt; Janet Carpenter
PURPOSES/AIMS: Breast cancer survivors comprise the largest group of cancer survivors with over 2.4 million female BCS living in the United States alone. Breast cancer survivors often experience frequent, severe, and bothersome symptoms that co-occur including hot flashes, mood disturbance, and cognitive dysfunction. One potential shared physiological mechanism underlying this symptom cluster is serotonin. Serotonin is a neurotransmitter that is synthesized, stored, and released by specific neurons in the brain and serotonin levels are significantly affected by estrogen withdrawal; a common side effect of breast cancer treatment. Based on this evidence, our lab has focused on a candidate gene approach to identify predictive physiologic and genetic biomarkers to further enhance our understanding of symptom pathophysiology and to provide insight to improve symptom management strategies.
RATIONALE/CONCEPTUAL BASIS/BACKGROUND: In a previous study with 300 breast cancer survivors starting on tamoxifen (anti-estrogen) therapy, we evaluated the association between SNPs in the serotonin receptors (HTR1A & HTR2A) and the serotonin synthesis pathway (TPH1). Although neither the TPH1 nor HTR1A genotypes were associated with hot flashes, the HTR2A genotypes were associated with therapy-induced hot flashes 3-months after starting treatment. In addition, in premenopausal women who received chemotherapy and were initiating tamoxifen, hot flashes were associated with the HTR2A C/T SNP rs#6313 genotype (Chemo: p=0.03). Similarly, the HTR2A rs#6313 C/T SNP and the rs#799701 A/G SNP in the same gene were also associated with tamoxifen-induced hot flashes in post-menopausal women.
METHODS: To further understand the role of serotonin in these common symptoms, we conducted a double-blind, crossover, randomized controlled trial that temporarily lowered central serotonin concentrations via acute tryptophan depletion (ATD) and explored genetic variation in response. Twenty female breast cancer survivors who were post-treatment for non-metastatic breast cancer received ATD or control in a double-blind, crossover design. Hot flashes were monitored continuously, mood disturbance was measured hourly, and cognitive performance was measured at the 5 hour tryptophan/serotonin nadir on each test day using standardized neuropsychological tests.
RESULTS: As anticipated, at +5 hour (nadir), the active amino acid drink resulted in 85% drop in tryptophan. However, the control drink also resulted in a 49% decrease in tryptophan. No significant changes in mood or hot flashes were noted. Significant cognitive impairment was noted in long-term memory (p = .04) and motor speed (p =.02) during ATD versus control. Due to small sample size no significant genetic variation was noted. Significant findings may have been difficult to detect due to the 49% drop in tryptophan seen with the control drink.
IMPLICATIONS: Findings from this series of studies will be used to further our understanding of the underlying mechanisms of these co-occurring cancer treatment-related symptoms. The premise that serotonin is involved in cognitive functioning of breast cancer survivors has important implications. First, it broadens our understanding of the potential underlying mechanisms involved with cognitive deficits. Secondly, such insights may help in identifying appropriate pharmacological (SSRIs) or non-pharmacological (dietary tryptophan) interventions that enhance performance. Further research in this area is needed to ultimately enhance breast cancer symptom management.
Repository Posting Date:
26-Oct-2011
Date of Publication:
17-Oct-2011
Sponsors:
Western Institute of Nursing

Full metadata record

DC FieldValue Language
dc.typePresentationen_GB
dc.titleCANDIDATE GENE APPROACH TO ENHANCE BREAST CANCER SYMPTOM MANAGEMENTen_GB
dc.identifier.urihttp://hdl.handle.net/10755/157388-
dc.description.abstract<table><tr><td colspan="2" class="item-title">CANDIDATE GENE APPROACH TO ENHANCE BREAST CANCER SYMPTOM MANAGEMENT</td></tr><tr class="item-sponsor"><td class="label">Conference Sponsor:</td><td class="value">Western Institute of Nursing</td></tr><tr class="item-year"><td class="label">Conference Year:</td><td class="value">2010</td></tr><tr class="item-author"><td class="label">Author:</td><td class="value">Von Ah, Diane, PhD, RN</td></tr><tr class="item-institute"><td class="label">P.I. Institution Name:</td><td class="value">Indiana University</td></tr><tr class="item-author-title"><td class="label">Title:</td><td class="value">Assistant Professor</td></tr><tr class="item-address"><td class="label">Contact Address:</td><td class="value">1111 Middle Drive, Indianapolis, IN, 46202, USA</td></tr><tr class="item-email"><td class="label">Email:</td><td class="value">dvonah@iupui.edu</td></tr><tr class="item-co-authors"><td class="label">Co-Authors:</td><td class="value">Todd Skaar; Fredrick Unverzagt; Janet Carpenter</td></tr><tr><td colspan="2" class="item-abstract">PURPOSES/AIMS: Breast cancer survivors comprise the largest group of cancer survivors with over 2.4 million female BCS living in the United States alone. Breast cancer survivors often experience frequent, severe, and bothersome symptoms that co-occur including hot flashes, mood disturbance, and cognitive dysfunction. One potential shared physiological mechanism underlying this symptom cluster is serotonin. Serotonin is a neurotransmitter that is synthesized, stored, and released by specific neurons in the brain and serotonin levels are significantly affected by estrogen withdrawal; a common side effect of breast cancer treatment. Based on this evidence, our lab has focused on a candidate gene approach to identify predictive physiologic and genetic biomarkers to further enhance our understanding of symptom pathophysiology and to provide insight to improve symptom management strategies. <br/>RATIONALE/CONCEPTUAL BASIS/BACKGROUND: In a previous study with 300 breast cancer survivors starting on tamoxifen (anti-estrogen) therapy, we evaluated the association between SNPs in the serotonin receptors (HTR1A &amp; HTR2A) and the serotonin synthesis pathway (TPH1). Although neither the TPH1 nor HTR1A genotypes were associated with hot flashes, the HTR2A genotypes were associated with therapy-induced hot flashes 3-months after starting treatment. In addition, in premenopausal women who received chemotherapy and were initiating tamoxifen, hot flashes were associated with the HTR2A C/T SNP rs#6313 genotype (Chemo: p=0.03). Similarly, the HTR2A rs#6313 C/T SNP and the rs#799701 A/G SNP in the same gene were also associated with tamoxifen-induced hot flashes in post-menopausal women. <br/>METHODS: To further understand the role of serotonin in these common symptoms, we conducted a double-blind, crossover, randomized controlled trial that temporarily lowered central serotonin concentrations via acute tryptophan depletion (ATD) and explored genetic variation in response. Twenty female breast cancer survivors who were post-treatment for non-metastatic breast cancer received ATD or control in a double-blind, crossover design. Hot flashes were monitored continuously, mood disturbance was measured hourly, and cognitive performance was measured at the 5 hour tryptophan/serotonin nadir on each test day using standardized neuropsychological tests.<br/>RESULTS: As anticipated, at +5 hour (nadir), the active amino acid drink resulted in 85% drop in tryptophan. However, the control drink also resulted in a 49% decrease in tryptophan. No significant changes in mood or hot flashes were noted. Significant cognitive impairment was noted in long-term memory (p = .04) and motor speed (p =.02) during ATD versus control. Due to small sample size no significant genetic variation was noted. Significant findings may have been difficult to detect due to the 49% drop in tryptophan seen with the control drink.<br/>IMPLICATIONS: Findings from this series of studies will be used to further our understanding of the underlying mechanisms of these co-occurring cancer treatment-related symptoms. The premise that serotonin is involved in cognitive functioning of breast cancer survivors has important implications. First, it broadens our understanding of the potential underlying mechanisms involved with cognitive deficits. Secondly, such insights may help in identifying appropriate pharmacological (SSRIs) or non-pharmacological (dietary tryptophan) interventions that enhance performance. Further research in this area is needed to ultimately enhance breast cancer symptom management.<br/></td></tr></table>en_GB
dc.date.available2011-10-26T19:49:40Z-
dc.date.issued2011-10-17en_GB
dc.date.accessioned2011-10-26T19:49:40Z-
dc.description.sponsorshipWestern Institute of Nursingen_GB
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