FUT2 gene polymorphism, gut microbiota composition and risk of colorectal adenomas
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Foley, Catherine. Fut2 Gene Polymorphism, Gut Microbiota Composition and Risk of Colorectal Adenomas. 2016. https://doi.org/10.17615/43qt-qc92APA
Foley, C. (2016). FUT2 gene polymorphism, gut microbiota composition and risk of colorectal adenomas. https://doi.org/10.17615/43qt-qc92Chicago
Foley, Catherine. 2016. Fut2 Gene Polymorphism, Gut Microbiota Composition and Risk of Colorectal Adenomas. https://doi.org/10.17615/43qt-qc92- Last Modified
- February 26, 2019
- Creator
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Foley, Catherine
- Affiliation: College of Arts and Sciences, Department of Biology
- Abstract
- Previous studies have investigated the relationship between blood type and pancreatic cancer, but little research has been done to determine how blood type correlates with the development of colon cancer. The fucosyltransferase2 (FUT2) gene is involved in the production and secretion of ABH blood group antigens along with mucin into the lumen of the colorectal tract. These antigens serve as carbon sources and anchoring sites for bacteria that are normally present in our gut and aid with digestion. However, a mutation in the FUT2 gene inhibits secretion of the ABH blood group antigens. The absence of these antigens could lead to a decrease in the number of normal bacteria in the gut, in turn allowing pathogenic, potentially cancer-causing, bacteria to colonize the colorectal tract. Therefore, we examined the relationship between the rs516246 SNP in the FUT2 gene, the microbial composition of the gut and the presence of colorectal adenomas (CRAs), which are precursors to colorectal cancer. We hypothesized that individuals with the variant allele (T) of the rs516246 SNP would be more likely to have CRAs and would have different bacterial profiles than those with the wildtype allele (C). We genotyped the rs516246 SNP and sequenced bacterial DNA in over 600 cases and controls using genomic DNA extracted from blood and biopsies respectively. We found no significant overall correlation between the variant genotype and the risk of developing CRAs, but that the variant genotype does affect the bacterial profile. Genotype was also linked to the level of expression of inflammation and mucin genes. It was expected that a change in the mucin secreted would increase inflammation in epithelial cells of the colorectal tract, because the mucus layer covering epithelial cells may be less capable of preventing pathogenic bacteria from penetrating the cells. While the presence of a T allele was significantly associated with increased expression of TLR4, which activates the immune system, it was also significantly associated with decreased expression of the inflammation marker IL-10. Our findings suggested that the rs516246 FUT2 variant alters bacterial composition and inflammation of the colorectal tract. Further studies are needed in order to analyze additional FUT2 SNPs and confirm their role in colorectal adenomas and cancer.
- Date of publication
- spring 2016
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- In Copyright
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- Funding: National Institute of Health
- Funding: Tom and Elizabeth Long Excellence Fund for Honors
- Advisor
- Keku, Temitope
- Degree
- Bachelor of Science
- Honors level
- Honors
- Degree granting institution
- University of North Carolina at Chapel Hill
- Extent
- 18
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