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Smoking, microsatellite instability & gastric cancers

Institution: University of Southern California
Investigator(s): Anna Wu, Ph.D.
Award Cycle: 2001 (Cycle 10) Grant #: 10RT-0251 Award: $729,199
Subject Area: Epidemiology
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Cigarette smoking has been associated with increased risks of cancers at many different sites including the stomach. However, the mechanism by which smoking influences gastric cancer development is not known. Cigarette smoking was recently shown to significantly increase the risk of microsatellite instability (MSI) in a study of sporadic colon cancer. MSI is a type of genetic change that is believed to promote cancer development by accelerating the accumulation of mutations. The role of MSI in gastric cancer is not known but it occurs quite frequently in gastric cancers. Another type of genetic change that is commonly found in colon and gastric cancer patients with MSI tumors is DNA methylation of the MLH1 gene (the MLH1 gene is commonly mutated in individuals with familial colon cancer and have MSI tumors). In addition, there is suggestive data that DNA methylation levels are higher among current smokers with lung cancer than never smokers with lung cancer. The relationship between MSI and smoking, DNA methylation and smoking, and the interrelationships between MSI, DNA methylation and smoking in gastric cancers are not known.

The objective of this proposed study is to expand a recently completed case-control study of some 700 gastric cancer patients in Los Angeles County by collecting tumor block materials. This will allow us to determine the prevalence of MSI and DNA methylation in these gastric cancer patients and to link the genetic information to smoking information and other lifestyle factors we have already collected. At the completion of this study, we will be able to determine on a population level the frequency of gastric cancers that show high level of MSI, low level of MSI, or no MSI. Using the information on smoking that has been collected, we will be able to address two questions: One, does cigarette smoking increase the risk of MSI in gastric tumors? Two, does cigarette smoking increase DNA methylation in tissues of gastric cancer patients? Addressing these questions will offer insights regarding the mechanism of smoking and will improve smoking education and prevention strategies.
Publications

A multiethnic population-based study of smoking, alcohol and body size and risk of adenocarcinomas of the stomach and esophagus (United States)
Periodical: Cancer Causes Control Index Medicus:
Authors: Wu AH, Wan P, and Bernstein L ART
Yr: 2001 Vol: 12 Nbr: Abs: Pg: 721 - 732

Role of helicobacter pylori CagA+ strains and risk of adenocarcinoma of the stomach and esophagus.
Periodical: International Journal of Cancer Index Medicus:
Authors: Wu AH, Crabtree JE, Bernstein L, Hawtin P, Cockburn M, Tseng CC, Forman D. ART
Yr: 2003 Vol: 103 Nbr: Abs: Pg: 815-821

Hiatal hernia, reflux symptoms, body size and risk of esophageal and gastric adenocarcinoma.
Periodical: Cancer Index Medicus:
Authors: Wu AH, Tseng CC, Bernstein L ART
Yr: 0 Vol: Nbr: Abs: Pg:

Hiatal hernia, reflux symptoms, body size, and risk of esophageal and gastric adenocarcinoma.
Periodical: Cancer Index Medicus:
Authors: Wu AH, Tseng CC, Bernstein L ART
Yr: 2003 Vol: 98 Nbr: Abs: Pg: 940-948

Etiologic clues from the similarity of histology specific trends in esophageal and lung cancers.
Periodical: Cancer Causes Control Index Medicus:
Authors: Cockburn MC, Wu AH, Bernstein L ART
Yr: 2005 Vol: 16 Nbr: Abs: Pg: 1065 - 1074

Occupational physical activity and risk of adenocarcinoma of the esophagus and stomach.
Periodical: International Journal of Cancer Index Medicus:
Authors: Vigen C, Bernstein L, Wu AH ART
Yr: 0 Vol: Nbr: Abs: Pg: