Browsing by Author "Shah, Ebony"

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    Identifying Racial/Ethnic Differences in Clinical Trial Enrollment, Drug Response, and Genetic Biomarkers of Taxane Induced Peripheral Neuropathy in African American Breast Cancer Patients
    (2021-08) Shah, Ebony; Skaar, Todd C.; Radovich, Milan; Quinney, Sara; Liu, Yunlong
    My first aim identified enrollment patterns and variables that predict enrollment in a diverse underserved population and evaluated barriers to enrollment. We analyzed data from the INGENIOUS, (Indiana GENomics Implementation and Opportunity for the UnderServed), pharmacogenomics implementation clinical trial conducted at a community hospital for underserved subjects and a statewide healthcare system. Our main finding revealed, African-Americans were less likely to refuse the study than non-Hispanic Whites (Safety net, OR =0.68, p<0.002; Academic hospital, OR=0.64, p<0.001), using a logistic regression model. The most frequent barriers to enrollment included not being interested, being too busy, transportation, and illness in African-American and non-Hispanic White subjects. In conclusion, improving research awareness, widening the inclusion criteria, and hiring recruiters who represent potential enrollees, should improve enrollment in African-Americans and other diverse populations. My 2nd research aim evaluated racial/ethnic differences in pharmacokinetics, safety, efficacy, and pharmacogenetics in 213 new molecular entities (NMEs). The current approved drug label for NMEs between 2014 to 2018 was updated in the FDA database. A qualitative analysis revealed ~ 9% (n=20/213) of NMEs reported racial/ethnic differences in the approved product label for PK, safety, efficacy, and/or pharmacogenetics. In conclusion, evaluating racial/ethnic differences in drug exposure and response early in the drug development program is essential to providing recommendations for different racial/ethnic subpopulations. My final aim 3, identified genetic biomarkers of Taxane Induced Peripheral Neuropathy (TIPN) in African-American breast cancer patients. We used an innovative computational tool, ALDY, to identify genetic variants in CYP2C8, CYP3A4, and CYP3A5 in 207 breast cancer subjects. TaqMan SNP genotyping for SNP, rs776746 (T>C) was performed in 160 subjects. Subjects were collapsed into three metabolizer groups; normal, intermediate, and poor metabolizer to test the association of peripheral neuropathy, dose reductions and CYP2C8/CYP3A5 metabolizer status. A logistic regression revealed CYP2C8 metabolizer status is associated with grades 3-4 peripheral neuropathy (p=0.04, OR= 2.21). CYP2C8*2 was modestly associated with dose reductions. In conclusion, evaluating pharmacogenetic and pharmacokinetic studies of paclitaxel and CYP2C8 is important. These studies may lead to clinical actionable prescribing of paclitaxel and improve the tolerance and efficacy in African-American breast cancer patients.
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    Relationship between West African ancestry with lung cancer risk and survival in African Americans
    (SpringerLink, 2019-11) Mitchell, Khadijah A.; Shah, Ebony; Bowman, Elise D.; Zingone, Adriana; Nichols, Noah; Pine, Sharon R.; Kittles, Rick A.; Ryan, Bríd M.; Medical and Molecular Genetics, School of Medicine
    Purpose: African Americans, especially men, have a higher incidence of lung cancer compared with all other racial and ethnic groups in the US. Self-reported race is frequently used in genomic research studies to capture an individual's race or ethnicity. However, it is clear from studies of genetic admixture that human genetic variation does not segregate into the same biologically discrete categories as socially defined categories of race. Previous studies have suggested that the degree of West African ancestry among African Americans can contribute to cancer risk in this population, though few studies have addressed this question in lung cancer. Methods: Using a genetic ancestry panel of 100 SNPs, we estimated West African, European, and Native American ancestry in 1,407 self-described African Americans and 2,413 European Americans. Results: We found that increasing West African ancestry was associated with increased risk of lung cancer among African American men (ORQ5 vs Q1 = 2.55 (1.45-4.48), p = 0.001), while no association was observed in African American women (ORQ5 vs Q1 = 0.90 (0.51-1.59), p = 0.56). This relationship diminished following adjustment for income and education. Conclusions: Genetic ancestry is not a major contributor to lung cancer risk or survival disparities.