Individualized Cancer Treatment based on Pharmacogenomics Analysis

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CONFERENCE: Appalachian Student Research Forum

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Balagoni, Harika; Mando, Rufaat; Reddy, Keerthy; Bansal, Apurva; Aregbe, Adegbemisola; Bajaj, Kailash; Zheng, Shimin; Dula, Mark; Kozinetz, Claudia; Cuervo-Pardo, Nathaly; Young, Mark; Reddy, Chakradhar; Gonzalez-Estrada, Alexei Show More Hide
diabetes mellitus; auditory processing; audiology; APD; posttraumatic growth; shame; guilt; veterans; time; healing; binge drinking; child sexual abuse; nutrition; students; speech language pathology; HIV; AIDS; metabolic hormones; metabolic syndrome; hispanic children; Tennessee; epidemiological study; heat effects; rural populations; urban heat island effect; UHI; elevated temperatures; heat mortality; urban popluations; vulnerability; adaptive capacity; sub-populations; relative risk; YouTube; technology; irritable bowel syndrome; IBS; asthma; obesity; sleep loss; physical activity; substance use; United States; adolescents; YRBS; Youth Risk Behavior Survey; sexual abuse; exposure; parental substance abuse; childhood; drunk driving; US; adults; Aedes aegypti; A. aegypti; infectious disease modeling; climate change; Maxent; human population density; heavy alcohol consumption; coronary heart disease; BRFSS; Behavioral Risk Factor Surveillance System; substrate specificity; kinetic properties; flavonol-3-O-glucosyltransferase; citrus paradisi; enzymes; GTs; glucosyltransferases; UDP-activated glucose; first generation; second generation; hispanic adolescents; united states; national survey of children's health; 2011-2012; suicide risk; self-compassion; effects; buprenorphine; methadone; hypertension; opioid dependence; Individualized cancer treatment; pharmacogenomics analysis; bullying; victimization; failure to use condom; sexual intercourse; US high school students; eosinophilic esophagitis; educational quality; information; narrative skills; children; specific language impairment; language; Behavior and Behavior Mechanisms; Biostatistics; Epidemiology; Substance Abuse and Addiction; Health Psychology; Public Health; Gastroenterology; Oncology; Pharmacy and Pharmaceutical Sciences; Cardiovascular System; Musculoskeletal Diseases; Speech Pathology and Audiology; Environmental Health and Protection; Environmental Monitoring; Environmental Policy; Environmental Public Health; Environmental Studies; Speech and Hearing Science; Biochemistry; Molecular Biology; Plant Biology; Endocrinology, Diabetes, and Metabolism; Cardiovascular Diseases
lecture / presentation description
5-Fluorouracil (5-FU) is one of most frequently used chemotherapeutic medications for the treatment of many types of cancer in curative and palliative setting. It is important to recognize chemotherapy side effects and toxicities because some of these symptoms may indicate a clinical syndrome needing evaluation for a principal cause. We discuss a patient who developed severe mucositis requiring hospitalization after first use of Fluorouracil. Dihydropyrimidine dehydrogenase ( DPD) deficiency was suspected and was proven to be a cause of severe drug-related toxicity. Our patient is fifty six year old gentleman with stage III nasopharyngeal squamous cell carcinoma who developed two masses on right side of the neck and large posterior right nasopharyngeal mass. Patient was treated with concurrent chemotherapy with high dose of cisplatin along with radiation. Once completion of concurrent chemotherapy and radiation he was started on combination of 5-Fluorouracil and cisplatin. Three days after completion of ninety six hour continuous 5-flurouracil infusion patient developed severe mucositis. Clinical exam was consistent with swollen tongue and mouth and inability to clear oral secretions. Patient was tested for DPYD gene mutation. Testing showed heterozygous for the c.1679T>G(*13) variant in the DPYD gene consistent with predicted intermediate DPD activity (30-70% enzyme activity). About 80% of administered 5-fluorouracil is normally inactivated by DPD. A decrease in DPD enzymatic activity may lead to increased concentrations of 5-FU and elevated risk for severe toxicities. Standard dose of 5-FU was decreased by 50% with second cycle of chemotherapy. Patient tolerated the second cycle of chemotherapy well. Variants in the DPD gene can lead to reduced 5-FU catabolism resulting in severe toxicities. Some of the toxicities can cause death. It is important to screen for this deficiency and closely observe patients during chemotherapy treatment.