Lung cancer is a leading cause of cancer in the United States and accounts for more deaths than prostate, breast, and colorectal cancers combined. Genetic variation has been known to play a role in lung cancer survival and risk. Furthermore, a racial disparity exists in lung cancer risk and survival such that African American males have increased risk and greater mortality compared to other U.S. racial/ethnic groups. This dissertation sought to expand our present understanding of the role of genetics in lung cancer survival and risk in African Americans. In a population of African Americans and whites from the Southern Community Cohort Study (SCCS), we examined the association between global African ancestry and overall survival and found no significant association. Stage and treatment, however, were strong predictors of overall survival. Since both stage and treatment are highly dependent on external social factors such as access to healthcare and willingness to seek treatment, we conclude that the observed racial disparity in lung cancer survival is strongly driven social determinants. We next examined genetic variants associated with lung cancer survival in the SCCS African Americans. We identified rs1878022 to be significantly associated with lung cancer survival, though in opposing direction to a previous study in whites. We also identified a region on chromosome 6p21.33 as suggestive of association with lung cancer survival. Finally, we sought to identify cross-cancer pleiotropic associations of lung cancer risk in African Americans by examining variant regions previously associated with cancer risk. We confirmed previous associations between chromosomes 15q25 and 5p15 and lung cancer risk. We also identified a peak on chromosome 16q22.2 significantly associated with increased lung cancer risk. Cumulatively these findings deepen our understanding of the role of genetics in both lung cancer risk and survival, particularly in African Americans. Future studies in African Americans are necessary to confirm these genetic associations.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-08022017-161854 |
| Date | 03 August 2017 |
| Creators | Jones, Carissa Christine |
| Contributors | Jeffrey Blume, Eric Grogan, Scott Williams, Digna Velez Edwards, Melinda Aldrich |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-08022017-161854/ |
| Rights | restrictone, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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