Barrett's esophagus (BE), a prelimalignant disease predisposing to human esophageal adenocarcinoma (EAC), is known to predominantly afflict Caucasian Americans. Our preliminary data have shown that in human BE a series of genes and pathways are activated to mediate the process of intestinal metaplasia, and thatintestinal transcription factors (e.g., Cdxl and Cdx2) are crucial to this process. Both Cdxl and Cdx2 are induced and expressed in esophageal epithelial cells through loss ef promoter methylation. Transfection of Cdx2 into human esophageal squamous epithelial cells induces metaplastic changes in morphology and gene expression, in this proposal, we hypothesize that environmental factors, genetic factors, and potentially gene-environment interactions play crucial roles in the observed racial disparity in BE. Clinical data, gastric secretions, endoscopic biopsy samples and blood samples will be collected from Caucasian and African American patients to identify critical environmental and genetic factors leading to BE. We hypothesize that differential distribution of genetic risk factors make Caucasian Americans more susceptible to BE than African Americans. Understanding the pathogenesis of the lesion is vital to future attempts at preventing metaplastic and dysplastic changes in the esophagus.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
1U54CA156735-01
Application #
8068482
Study Section
Special Emphasis Panel (ZCA1-SRLB-3 (O1))
Project Start
2010-09-01
Project End
2013-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
1
Fiscal Year
2010
Total Cost
$358,116
Indirect Cost
Name
North Carolina Central University
Department
Type
DUNS #
783691801
City
Durham
State
NC
Country
United States
Zip Code
27707
Kilfoyle, Kimberly A; Des Marais, Andrea C; Ngo, Mai Anh et al. (2018) Preference for Human Papillomavirus Self-Collection and Papanicolaou: Survey of Underscreened Women in North Carolina. J Low Genit Tract Dis 22:302-310
Xiong, Zhaohui; Ren, Shuang; Chen, Hao et al. (2018) PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium. J Pathol 244:164-175
Ahmad, Syed; St Hilaire, Valentine R; Dandepally, Srinivasa R et al. (2018) Discovery and characterization of an iminocoumarin scaffold as an inhibitor of MEKK2 (MAP3K2). Biochem Biophys Res Commun 496:205-211
Butler, EboneƩ N; Bensen, Jeannette T; Chen, Mengjie et al. (2018) Prediagnostic Smoking Is Associated with Binary and Quantitative Measures of ER Protein and ESR1 mRNA Expression in Breast Tumors. Cancer Epidemiol Biomarkers Prev 27:67-74
Des Marais, Andrea C; Zhao, Yuqian; Hobbs, Marcia M et al. (2018) Home Self-Collection by Mail to Test for Human Papillomavirus and Sexually Transmitted Infections. Obstet Gynecol 132:1412-1420
DeBono, Nathan L; Robinson, Whitney R; Lund, Jennifer L et al. (2018) Race, Menopausal Hormone Therapy, and Invasive Breast Cancer in the Carolina Breast Cancer Study. J Womens Health (Larchmt) 27:377-386
Ma, Shaohua; Paiboonrungruan, Chorlada; Yan, Tiansheng et al. (2018) Targeted therapy of esophageal squamous cell carcinoma: the NRF2 signaling pathway as target. Ann N Y Acad Sci 1434:164-172
Kienka, Tamina; Varga, Matthew G; Caves, Josie et al. (2018) Epstein-Barr virus, but not human cytomegalovirus, is associated with a high-grade human papillomavirus-associated cervical lesions among women in North Carolina. J Med Virol :
Bruno, Robert D; Fleming, Jodie M; George, Andrea L et al. (2017) Mammary extracellular matrix directs differentiation of testicular and embryonic stem cells to form functional mammary glands in vivo. Sci Rep 7:40196
Ma, Zhikun; Parris, Amanda B; Xiao, Zhengzheng et al. (2017) Short-term early exposure to lapatinib confers lifelong protection from mammary tumor development in MMTV-erbB-2 transgenic mice. J Exp Clin Cancer Res 36:6

Showing the most recent 10 out of 72 publications