Date of Award
Fall 8-17-2026
Embargo Period
12-31-2030
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Public Health Sciences
College
College of Graduate Studies
First Advisor
Kristin Wallace
Second Advisor
Alexander Alekseyenko
Abstract
Background: Cigarette smoking increases risk of colorectal cancer (CRC) and preinvasive lesions and aberrant host immune responses may be involved. This dissertation evaluated whether smoking impacted mean T-cell densities and gene expression, whether smoking increased risk of metachronous lesions and whether this was mediated by the immune response. These analyses used preinvasive lesions from over 400 participants of 3 completed epidemiological studies.
Methods: Gene expression and mean T-cell densities were examined using the NanoString nCounter platform and the Akoya and Visiopharm software. To complete these aims, we used 1) generalized linear mixed models with a log link and negative binomial distribution, using log of the total cell area as an offset, 2) distance-based multivariate analysis of variance tests and 3) logistic regression, multinomial regression and causal mediation analysis. Analyses were adjusted for age, sex and histologic type.
Results: Mean densities of T-cell subtypes CD8+ and Tc17 differed by smoking duration. For gene expression, innate and adaptive profile expression significantly differed by smoking metrics in former smokers, but not current smokers. For risk of metachronous lesions, ever, former, long duration, and high intensity smoking showed increased risk of multiple lesions at follow-up. In causal mediation analysis, we observed no significant mediating effects.
Conclusions: These analyses showed that smoking impacts innate and adaptive immune responses within the TiME of preinvasive colorectal lesions and increases risk of multiple metachronous lesions. These results motivate detailed exploration on mechanisms for smoking-associated CRC risk and may provide clues for future immune-focused CRC prevention strategies.
Recommended Citation
Fanning, Lauren R., "Cigarette Smoking and the Immune Contexture in Preinvasive Colorectal Lesions: Associations and Causal Mediation Analysis for Risk of Metachronous Lesions" (2026). MUSC Theses and Dissertations. 1145.
https://medica-musc.researchcommons.org/theses/1145
Rights
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