M11 - NCI - Upper GI cancer GWAS and telomere length evaluation (includes M10)

Investigator Names and Contact Information

Phil Taylor (ptaylor@nih.gov)

Introduction/Intent

Gastric cancer is the fourth most common incident cancer and the second leading cause of cancer death in the world. Most cohort studies, such as WHI, were initiated in populations at lower risk for gastric cancer, resulting in small case numbers in most cohort studies. Small case numbers have severely limited the power of prospective studies. We propose a collaborative project in the Cohort Consortium to develop a large nested case-control study by pooling prospectively collected specimens from multiple cohort studies, which can be used to conduct studies of gastric cancer. With almost 2500 prospectively collected cases with available sources of blood and DNA, this project would provide a rich and unique resource for helping to clarify the association of suspected gastric cancer risk factors and for identifying new risk factors.

As a proof of principle, we propose three projects: 1) to examine the association between pepsinogen I/II ratio with gastric cancer risk; 2) alcohol intake, polymorphisms in alcohol metabolizing genes with gastric cancer risk; and 3) germline telomere length with gastric cancer risk.

Aims We propose to study the following specific aims in a pooled nested case-control study of gastric cancer within the cohort consortium gastric cancer project:

1. To evaluate the association between pepsinogen I/II and gastric cancer risk, and determine whether the association varies by anatomic-subsite.
2. To evaluate the interaction between alcohol intake, SNPs in alcohol metabolizing genes, and gastric cancer risk.
3. To evaluate the association between germline telomere length and risk of gastric cancer; as well as explore whether this association is modified by factors associated with chronic inflammation/oxidative stress, such as H. pylori infection, and chronic gastric atrophy.

Gastric cancer remains the second leading cause of cancer-related mortality worldwide¹. Rates are generally higher in developing countries, and lower in North American and Western European countries. Most cohort studies were initiated in populations at lower risk for gastric cancer. As such, case numbers are small in most cohort studies, leading to limited power to investigate moderate risk factors. Furthermore, most previous cohort studies have not measured H. pylori infection and so cannot adjust risk estimates for this very important gastric cancer risk factor. We plan to measure H. pylori in the consortium so as to be able to adjust our analyses for this risk factor.