Esophageal adenocarcinoma (EA) has the fastest rising incidence of all cancers in the United States. The overall annual incidence has more than tripled over a twenty year period. These statistics imply an urgent problem that needs addressing, and an environmental component to the etiology and pathogenesis of EA. Although gastroesophageal reflux disease, Barrett's esophagus and obesity are known risk factors for EA, more recently, a protective effect for Helicobacter pylori (HP) has been hypothesized based on the results of several studies. One objective of this research is to confirm earlier results in a large sample of over 250 histologically-confirmed incident EA cases. Through a secondary analysis of data and specimens from two separate molecular epidemiologic studies, the association between Helicobacter pylori and EA risk will be examined via a case-control design, after taking into account important covariates such as gastroesophageal reflux, Barrett's esophagus, and body-mass index. In addition, there may be host factors such as genetic polymorphisms that modify the relationship between HP and EA risk. Genetic polymorphisms involved in three pathways will be evaluated as potential modifiers of this relationship: (a) genes in the inflammatory pathway, such as IL1-beta; (b) genes involved in free radical formation such as MPO and MnSOD; and (c) several candidate DNA repair genes. Both single nucleotide polymorphisms and haplotypes will be evaluated as potential modifiers of the HP-EA risk association. One long-term goal of this small grant project is to generate information that will ultimately lead to a more comprehensive large scale population-based case-control study of EA risks. This application addresses directly priorities set by the NCl, in particular, the recommendations of the Stomach and Esophageal Cancer Progress Report Group (2002), and may have important impact on current medical practices related to the aggressiveness of treating HP infections.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
1R03CA110822-01
Application #
6840282
Study Section
Special Emphasis Panel (ZCA1-SRRB-Q (M1))
Program Officer
Starks, Vaurice
Project Start
2004-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$87,250
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Zhai, Rihong; Zhao, Yang; Liu, Geoffrey et al. (2012) Interactions between environmental factors and polymorphisms in angiogenesis pathway genes in esophageal adenocarcinoma risk: a case-only study. Cancer 118:804-11
Cheung, Winson Y; Zhai, Rihong; Bradbury, Penny et al. (2012) Single nucleotide polymorphisms in the matrix metalloproteinase gene family and the frequency and duration of gastroesophageal reflux disease influence the risk of esophageal adenocarcinoma. Int J Cancer 131:2478-86
Zhai, Rihong; Zhao, Yang; Su, Li et al. (2012) Genome-wide DNA methylation profiling of cell-free serum DNA in esophageal adenocarcinoma and Barrett esophagus. Neoplasia 14:29-33
Wu, I-Chen; Zhao, Yang; Zhai, Rihong et al. (2011) Association between polymorphisms in cancer-related genes and early onset of esophageal adenocarcinoma. Neoplasia 13:386-92
Zhai, Rihong; Chen, Feng; Liu, Geoffrey et al. (2010) Interactions among genetic variants in apoptosis pathway genes, reflux symptoms, body mass index, and smoking indicate two distinct etiologic patterns of esophageal adenocarcinoma. J Clin Oncol 28:2445-51
Liu, Chen-Yu; Wu, Michael C; Chen, Feng et al. (2010) A Large-scale genetic association study of esophageal adenocarcinoma risk. Carcinogenesis 31:1259-63
Cheung, Winson Y; Zhai, Rihong; Kulke, Matthew H et al. (2009) Epidermal growth factor A61G gene polymorphism, gastroesophageal reflux disease and esophageal adenocarcinoma risk. Carcinogenesis 30:1363-7
Bradbury, Penelope A; Zhai, Rihong; Ma, Clement et al. (2009) Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis. Clin Cancer Res 15:4680-5
Lanuti, Michael; Liu, Geoffrey; Goodwin, Jonathan M et al. (2008) A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome. Clin Cancer Res 14:3216-22
Asomaning, Kofi; Reid, Amy E; Zhou, Wei et al. (2008) MDM2 promoter polymorphism and pancreatic cancer risk and prognosis. Clin Cancer Res 14:4010-5

Showing the most recent 10 out of 14 publications