Grant Number:	5R03CA110822-02 Interpret this number
Primary Investigator:	Liu, Geoffrey
Organization:	Massachusetts General Hospital
Project Title:	H.pylori, Genes and Esophageal Adenocarcinoma
Fiscal Year:	2005

DESCRIPTION (provided by applicant): 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.





None