Browsing by Subject "race/ethnicity"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Ethnic differences in the metabolism of 1,3-butadiene and lung cancer risk
    (2019-01) Boldry, Emily
    Cigarette smoking remains one of the most preventable causes of death in the world, and is the leading cause of lung cancer. Epidemiological studies show inherent differences in lung cancer risk among smokers of different ethnic groups, with Native Hawaiian and African Americans have the highest risk, European Americans having an intermediate risk, and Latinos and Japanese Americans having the lowest risk. It has been proposed that these disparities in risk are due to ethnic differences in the metabolism, and ultimately bioactivation, of carcinogens in present in cigarette smoke. 1,3-butadiene (BD) is one of the most abundant and potent carcinogens present in cigarette smoke. BD is metabolically activated to the reactive species 3,4-epoxy-1-butene (EB), hydroxymethylvinylketone (HMVK), 3,4-epoxy-1,2-butanediol (EBD), and 1,2,3,4-diepoxybutane (DEB), which have the ability to form pro-mutagenic DNA adducts. These species can be detoxified through glutathione conjugation and excreted in urine; EB and HMVK are excreted as 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/ 1-(N-acetyl-L-cystein-S-yl)-2-hydroxybut-3-ene (MHBMA) and 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA). The research presented in this thesis focuses on ethnic differences in BD metabolism and the initial development of a DEB specific biomarker. A high throughput HPLC-ESI--MS/MS method for the simultaneous quantitation of MHBMA and DHBMA in humans previously developed in our laboratory was applied to quantify these mercapturic acids in smokers of different ethnic groups. In a large multi-ethnic study composed of African American, European American, and Japanese American smokers (N = 1,072). Urinary MHBMA and MHBMA/MHBMA+DHBMA were highest in African Americans, followed by European Americans, and Japanese Americans, and strongly influenced by GSTT1 genotype. A genome wide association study (GWAS) revealed strong associations between MHBMA and GSTT1: associations with 136 SNPs were detected, and all of them were located between 24.2—24.4 Mb near the GSTT1 gene on chromosome 22q11. Additional experiments with recombinant human GSTT1 and GSTT2 confirmed EB as a substrate for the first time. The same method was also applied to a separate smaller study of African American and European American smokers (N = 151). In contrast to the previous work, urinary MHBMA was higher in European Americans than African Americans in this study; this is likely due to decreased sample size. Statistical analyses revealed no correlation between urinary MHBMA or DHBMA and urinary N7-(1-hydroxy-3-buten-2-yl)guanine (EBGII), as well no significant associations between urinary EBGII, MHBMA, or DHBMA and various specific SNPs from BD-metabolizing genes (EPHX1 and CYP2E1) and DNA repair genes (FANCE). GSTT1 copy number was also included in this analysis, and showed a significant association with urinary MHBMA. Urinary MHBMA and DHBMA were also quantified in smokers (N=79) receiving treatment with the chemopreventative agent 2-phenethyl isothiocyanate (PEITC). Overall, PEITC treatment resulted in only slight increases in MHBMA and DHBMA as compared to treatment with a placebo, but was found to significantly increase MHBMA in individuals null for GSTT1 or both GSTT1 and GSTM1, indicating a potential protective effect of PEITC in these individuals. Lastly, an HPLC-ESI+-MS/MS method for the of detection of a novel DEB-specific biomarker, Nε, Nε-(2,3-dihydroxybutan-1,4-diyl)-L-lysine (DHB-Lys) was explored. Initial development focused on the use of an ion-pairing agent, perfluoroheptanoic acid (PFHA), which was chosen to increase HPLC retention of DHB-Lys. Though addition of PFHA to the aqueous mobile phase during HPLC-ESI+-MS/MS analysis did result in increased retention of the analyte, its use also presented additional challenges with analyte carryover, sample contamination, and ion suppression. Methodology utilizing derivatization of DHB-Lys through the addition of a 6-aminoquinolyl group (6-AQ) at the alpha nitrogen was tested on DEB-treated O6-alkylguanine DNA alkyltransferase (AGT), and showed a dose dependent increase in DHB-Lys formed.
  • Thumbnail Image
    Item
    Social Capital, Self-Control, and Academic Performance in School-Age Children and Adolescents: Patterns Associated with Race/Ethnicity
    (2018-11) Song, Wei
    Children’s abilities to control behaviors and emotions continue to grow from childhood to adolescence. The thesis examined the degree to which the social capital in family and school contexts shaped self-control among four racial/ethnic groups (i.e., Caucasian, African American, Hispanic, Asian American), and whether self-control served as a mediator of the relationship between social capital and academic performance. It consisted of two studies using two major datasets (Early Childhood Longitudinal Study – Kindergarten: 2011 and Minnesota Student Survey). Study 1 analyzed a nationally representative sample of children who entered kindergarten during the school year of 2010-2011, following them through second grade. Study 2 analyzed a statewide sample of adolescents in secondary schools (8th, 9th, and 11th grader) between 12 to 18 years old in 2016. In the investigation of racial/ethnic differences, first the measurement equivalence of family/school social capital, self-control, and academic performance were established in each study. Then multi-group Structural Equation Modeling (SEM) was conducted to assess whether racial/ethnic membership moderates proposed associations for children and adolescence. Study 1 found that family social capital positively predicted self-control and academic achievement for Caucasian and Hispanic children, while school social capital was not significant for any group. Self-control was a partial and positive mediator of the relationship between family social capital and academic achievement for the Caucasian and Hispanic children. Study 2 found positive associations from family and school social capital to self-control, and self-control partially and significantly mediated associations between social capital and academic achievement for adolescents across racial/ethnic groups. Implications for prevention, intervention, and public policy for different populations of interest are provided.