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 Cdx1 and Cdx2 are induced and expressed in esophageal epithelial cells through loss of 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 #
5U54CA156733-02
Application #
8329641
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$395,586
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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
Puvanesarajah, Samantha; Nyante, Sarah J; Kuzmiak, Cherie M et al. (2018) PAM50 and Risk of Recurrence Scores for Interval Breast Cancers. Cancer Prev Res (Phila) 11:327-336
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
Smith, Jennifer S; Des Marais, Andrea C; Deal, Allison M et al. (2018) Mailed Human Papillomavirus Self-Collection With Papanicolaou Test Referral for Infrequently Screened Women in the United States. Sex Transm Dis 45:42-48
Williams, Lindsay A; Nichols, Hazel B; Hoadley, Katherine A et al. (2018) Reproductive risk factor associations with lobular and ductal carcinoma in the Carolina Breast Cancer Study. Cancer Causes Control 29:25-32
Troester, Melissa A; Sun, Xuezheng; Allott, Emma H et al. (2018) Racial Differences in PAM50 Subtypes in the Carolina Breast Cancer Study. J Natl Cancer Inst 110:
Anderson, Chelsea; Breithaupt, Lindsay; Des Marais, Andrea et al. (2018) Acceptability and ease of use of mailed HPV self-collection among infrequently screened women in North Carolina. Sex Transm Infect 94:131-137
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
Jiang, Ming; Li, Haiyan; Zhang, Yongchun et al. (2017) Transitional basal cells at the squamous-columnar junction generate Barrett's oesophagus. Nature 550:529-533

Showing the most recent 10 out of 49 publications