Abstract

Abstract The major research focus of this project is the identification of genetic variants involved in disparities in carcinogen metabolism and risk for cancer. Specifically, this research focuses on the identification of genetic variants in carcinogen metabolism genes, that increase lung cancer risk, particularity when the risk differs between men and women or by racial groups. Although cigarette smoking causes the vast majority of lung cancers, most lifetime smokers do not develop this disease. Many studies suggest that women have greater susceptibility than men for lung cancer, and that risk varies by racial groups. Genetic variation in tobacco carcinogen-metabolizing enzymes could give details as to why only some smokers develop lung cancer and why women or certain racial groups may be at a greater risk. Genetic changes have been shown to vary significantly between individuals of different races, which could contribute to racial disparities in cancer risk. Uridine glucuronosyltransferase (UGT) genes detoxify many carcinogens found in tobacco, so variants in UGT genes could explain differences in lung cancer risk among smokers. Many genetic association studies of UGT genes and lung cancer risk have been performed to identify alleles (SNPs and Copy Number Variants) in UGT genes that increase risk for lung cancer, and to determine if some variants display a gender or racial-specific association with this cancer. cBioPortal provides gene-based visualizations and analyses, so that users can find altered genes and/or networks within a study of interest or across all cancer studies. cBioPortal is a web application platform that facilitates data exploration and analysis through the use of a variety of visualization and analytical tools using populations of cancer cases and controls. cBioPortal has been utilized in this study to visualize variations in UGT genes across many lung cancer data sets. A copy number variant that deletes the entire UGT2B17 gene (which metabolizes the lung cancer carcinogen, NNAL) is a particular focus in this study using data from cBioPortal, as well as common copy number alterations (amplifications) in UGT3A1 and UGT3A2. Citation Format: James W. Gallagher, Talayshia Vicks, Carla J. Gallagher. Lung cancer risk in women and racial minorities and genetic variants of UGT genes [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B069.

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