Genetic ancestry and population health: elucidating the relative role of African genetic ancestry in cancer genomics and the broader implications for racial health disparities in cancer

Racial health disparities in cancer remain a persistent and deeply rooted issue disproportionately affecting minoritized populations in the United States. Among these groups, individuals of African ancestry, particularly African Americans, face some of the most severe outcomes, including higher incidence rates, delayed diagnoses, poorer prognoses, reduced survival, and less effective responses to treatment. While historical and systemic inequities in healthcare, as well as socioeconomic factors such as income, education, and access to care, have long been cited as major contributors, mounting evidence suggests that these disparities persist even after controlling for these variables. This persistence demonstrates that additional biological factors, including ancestry-associated genetic variation, may play a critical and underexplored role in shaping cancer risk and outcomes. This thesis investigates how ancestry-linked genetic variants may contribute to cancer development, progression, and disparities between human populations, particularly those found in populations of African ancestry. The central objective is to determine whether African ancestry-informative markers (AIMs) directly or indirectly influence molecular mechanisms implicated in cancer biology and to assess whether these markers are broadly relevant across multiple cancer types or demonstrate specificity to particular malignancies. Identifying the extent and nature of these associations will improve our understanding of where disparities are primarily driven by ancestry-linked biology and where external factors exacerbate them. Additionally, this work examines the impact of environmental exposure on cancer risk through the lens of gene-environment interactions. Complicating the investigation into disease variation is the fact that environmental and genetic factors can interact cooperatively to influence disease risk in a manner that would not occur independently. Such insight is crucial for developing and implementing equitable strategies in cancer prevention, diagnosis, treatment, and precision medicine. To accomplish these goals, the thesis employs a multi-pronged methodological framework, beginning with a comprehensive literature review that situates AIMs within the broader discourse on cancer health disparities and genomic equity. Chapter 1 focuses on the functional characterization of a large panel of African AIMs, assessing their potential biological roles in cancer-relevant pathways. The results show these AIMs, distributed throughout the genome, were effective in separating populations of African ancestry from others. Some of these markers are linked to genes, many of which have been documented to be involved in various cancers. However, only a small percentage of these markers are located in the coding region of the genome, making it challenging to characterize and annotate the vast majority of them. Chapter 3 extends this analysis through a comprehensive eQTL analysis of seven different cancers with documented racial health disparities. The study focused on markers in non-coding regions of the genome and examined whether these markers disrupt key processes, such as gene expression. This work identified 196 SNPs acting as cis- or trans-eQTLs across the various cancers, with the bulk of the interactions being tissue-specific. Only 13 of the SNPs were found as eQTL in 3 or more cancers. The associated eGenes were involved in a wide array of biological functions, with many implicated in the cancer machinery, such as tumor suppression, cell proliferation, and DNA repair. Chapter 4 explores how genetic factors interact with environmental exposures through a genome-wide gene-by-environment interaction study (GEWIS), querying how lifestyle choices may mediate the impact of genetic factors on cancer susceptibility. From this GEWIS, multiple novel markers were found to significantly increase head and neck cancer risk, with rs74125744 and rs11804045 remaining statistically significant after controlling for multiple testing. The SNPs influencing head and neck cancer risk through interaction with tobacco exposure did not meet the genome-wide threshold for significance. However, a few were highlighted as suggestive associations worthy of further investigation, as they are linked to genes implicated in critical pathways. Whether they were found to be associated with increased cancer risk through SNP-only or SNP-by-tobacco exposure interactions, the reported markers were involved in key mechanisms, including genome integrity, transcriptional control, and protein synthesis, which, when altered, can promote tumorigenesis. One of these markers is particularly compelling, as it maps to an intronic region of a tumor-promoting gene with documented changes in expression in response to tobacco smoke exposure. Altogether, these integrated analyses provide novel insights into how African ancestry influences molecular and cellular processes relevant to cancer. By approaching African AIMs from multiple biological and contextual angles, this thesis contributes to a more nuanced and comprehensive understanding of how genetic ancestry intersects with cancer biology and health disparities. The findings of this work reinforce the urgency of diversifying genomic research, tailoring biomedical tools to ancestrally diverse populations, and adopting inclusive frameworks in precision medicine. Using AIMs, this thesis seeks to illuminate the molecular consequences of African ancestry for cancer risk and outcomes, and to inform future research, policy, and clinical practice dedicated to mitigating racial health disparities in cancer.

Grantor dc:publisher

Temple University. Libraries

Year dc:date.issued

2026

Author dc:creator

• Boudeau, Samantha

Advisors dc:contributor.advisor

• Kulathinal, Rob J.
• Ragin, Camille

Committee members dc:contributor.committeemember

• Pond, Sergei
• Hey, Jody
• Lachance, Joseph
• Shi, Xinghua Mindy

• Bioinformatics
• Biomedical sciences

Statement dc:rights

• IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available.

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

eng

Repository record dc:identifier.uri

https://scholarshare.temple.edu/handle/20.500.12613/12125

OAI identifier oai:identifier

oai:scholarshare.temple.edu:20.500.12613/12125