Study
PLCO
(Learn more about this study)
Project ID
2008-0210
Initial CDAS Request Approval
Jan 23, 2009
Title
Role of chronic inflammation and oxidative stress on telomere length and risk of gastric cancer
Summary
Chronic inflammation and oxidative stress, due to factors such as H. pylori infection and smoking, are critical risk factors in the etiology of gastric cancer. Telomere shortening may be increased among individuals with increased chronic inflammation, such as chronic gastric atrophy- a precursor of gastric cancer. Recently, telomere length has been suggested to be a predictor of risk in several small studies of cancer, mostly case-control studies in which DNA samples were collected after cancer diagnosis. Furthermore, the pathway from exposure to shortened telomere length and subsequent elevated cancer risk has not been well examined, particularly for gastric cancer for which no evaluation of germline telomere length has been conducted to date. The purpose of this study is to investigate whether telomere length is associated with gastric cancer risk and to relate measures of chronic inflammation and oxidative stress with telomere length. We are proposing a study to evaluate this hypothesis in gastric cancer cases and controls from four prospective studies: the Shanghai Women's Health Study (SWHS), the Multiethnic Cohort Study (MEC), the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), and the Women's Health Initiative (WHI). We propose to measure germline telomere length in a pooled nested case-control study to address the specific aims. Existing and study generated data on H. pylori status and virulence, gastric atrophy, markers of chronic inflammation and oxidative stress from prospectively collected specimens will be used. Knowledge gained from this study will provide important information on characterizing telomere length and its relation to gastric cancer.
Aims
We propose to study the following specific aims in 449 gastric cancer cases and 898 controls from a nested case-control study of gastric cancer within four prospective cohorts: 1. To evaluate the association between germline telomere length and risk of gastric cancer. 2. To explore whether the association between telomere length and risk of gastric cancer is modified by factors associated with chronic inflammation/oxidative stress, such as H. pylori infection, chronic gastric atrophy, plasma C-reactive protein (CRP) level, smoking status, and antioxidant intake. 3. To identify additional risk factors, such as gender or ethnicity, that may affect telomere length by examining the association between telomere length and chronic inflammation/oxidative stress among controls.
Collaborators
Wong-Ho Chow (NCI, DCEG)
Immaculata DeVivo (Harvard Medical School)
Linda Dong (NCI, DCEG)
Garnet Anderson (Fred Hutchinson Cancer Resarch Center)
Wen-Yi Huang (NCI, DCEG)
Meira Epplein (Cancer Research Center of Hawaii)
Sharon Savage (NCI, DCEG)
Nathaniel Rothman (NCI, DCEG)
