Browsing by Author "Ness, Reid M."

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    Comparison of Biomarker Expression between Proximal and Distal Colorectal Adenomas: The Tennessee-Indiana Adenoma Recurrence Study
    (Wiley, 2017-02) Su, Timothy; Washington, M. Kay; Ness, Reid M.; Rex, Douglas K.; Smalley, Walter E.; Ulbright, Thomas M.; Cai, Qiuyin; Zheng, Wei; Shrubsole, Martha J.; Medicine, School of Medicine
    It is unclear if proximal and distal traditional adenomas present with differences in molecular events which contribute to cancer heterogeneity by tumor anatomical subsite. Participants from a colonoscopy-based study (n=380) were divided into subgroups based on the location of their most advanced adenoma: proximal, distal, or “equivalent both sides”. Eight biomarkers in the most advanced adenomas were evaluated by immunohistochemistry (Ki-67, COX-2, TGFβRII, EGFR, β-catenin, cyclin D1, c-Myc) or TUNEL (apoptosis). After an adjustment for pathological features, there were no significant differences between proximal and distal adenomas for any biomarker. Conversely, expression levels did vary by other features, such as their size, villous component, and synchronousness. Large adenomas had higher expression levels of Ki-67(P<0.001), TGFβRII (P<0.0001), c-Myc (P<0.001), and cyclin D1 (P<0.001) in comparison to small adenomas, and tubulovillous/villous adenomas also were more likely to have similar higher expression levels in comparison to tubular adenomas. Adenoma location is not a major determinant of the expression of these biomarkers outside of other pathological features. This study suggests similarly important roles of Wnt/β-catenin and TGF-β pathways in carcinogenesis in both the proximal and distal colorectum.
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    Genome-wide association study identifies possible genetic risk factors for colorectal adenomas
    (American Association for Cancer Research, 2013) Edwards, Todd L.; Shrubsole, Martha J.; Cai, Qiuyin; Li, Guoliang; Dai, Qi; Rex, Douglas K.; Ulbright, Thomas M.; Fu, Zhenming; Delahanty, Ryan H.; Murff, Harvey J.; Smalley, Walter; Ness, Reid M.; Zheng, Wei; Pathology and Laboratory Medicine, School of Medicine
    Background: Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown. Methods: In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls. We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. Results: No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81-0.94; P = 4.4 × 10(-4)), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18-1.47; P = 1.1 × 10(-6)). Conclusions: This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies. Impact: These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis.