Thesis
TERT genetic polymorphisms and survival after colorectal cancer diagnosis
University of Iowa
Master of Science (MS), University of Iowa
Spring 2023
DOI: 10.25820/etd.007144
Abstract
Telomerase reverse transcriptase (TERT) has elevated expression in over 90% of cancers. The key role of TERT is as the catalytic protein subunit of the telomerase complex. Increasing expression of telomerase works against constant telomere erosion by increasing telomere length and allows a tumor cell to evade senescence and apoptosis. Variation within TERT has been linked to increased risk of colorectal cancer (CRC) development, and differences in CRC prognosis. In this thesis, we examine whether single nucleotide changes along the TERT gene have any relation to all-cause mortality after CRC diagnosis. Additionally, due to the differences in molecular patterns in cancers of the ascending and descending colon, relevant single nucleotide polymorphism (SNP) expression might vary based on the location of the primary tumor within the bowel. As a second aim, we examine whether the location of the tumor (ascending/ descending colon) influences TERT SNP survival associations. Finally, we examine if changes in the TERT gene influence telomere length. We found limited support that TERT SNPs may have an association with CRC survival. Similarly, we found no association between any TERT SNPs and overall or CRC-specific survival from CRC diagnosed in any region of the colon. There is some support for the hypothesis that TERT SNPs have an association with telomere length, though this is known to be polygenic.
Details
- Title: Subtitle
- TERT genetic polymorphisms and survival after colorectal cancer diagnosis
- Creators
- Seth Borrowman
- Contributors
- Michael O'Rorke (Advisor)Sarah Nash (Committee Member)Hatem El-Shanti (Committee Member)
- Resource Type
- Thesis
- Degree Awarded
- Master of Science (MS), University of Iowa
- Degree in
- Epidemiology
- Date degree season
- Spring 2023
- Publisher
- University of Iowa
- DOI
- 10.25820/etd.007144
- Number of pages
- x, 47 pages
- Copyright
- Copyright 2023 Seth Borrowman
- Language
- English
- Date submitted
- 04/25/2023
- Date approved
- 05/10/2023
- Description illustrations
- Illustrations, tables, graphs, charts
- Description bibliographic
- Includes bibliographical references (pages 34-38).
- Public Abstract (ETD)
Colorectal cancer (CRC) is a disease of the large intestine (colon) and/or the region connecting the colon to the anus (rectum). CRC is one of the most common cancers worldwide and the second deadliest. One method to reduce CRC mortality and morbidity is to identify biological markers (biomarkers) that indicate a person has increased risk of dying from a specific cancer.
Our DNA is wound tightly within our cells into structures called chromosomes. End caps on these chromosomes called telomeres serve as a protective feature of the DNA – just like plastic caps on shoelaces. Telomeres get shortened each time a cell divides, and when they get too short, a normal cell would die. Cancer cells have found ways to keep these telomeres extra-long so that they can stay alive and produce more cancer cells.
A gene called TERT produces a protein that helps build these telomeres. Changes, called SNPs, along this gene can change its function. Our study seeks to understand if any of these SNPs can change our risk of dying after CRC diagnosis and if they change the length of our telomeres.
We found no evidence that variation within TERT is associated with how long CRC patients survive after diagnosis. This finding was the same even after we broke the analysis down by what part of the intestine the cancer was in. We did find some evidence that TERT SNPs are associated with telomere length.
- Academic Unit
- Epidemiology
- Record Identifier
- 9984425313302771
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