Study
PLCO
(Learn more about this study)
Project ID
2011-0191
Initial CDAS Request Approval
Aug 31, 2011
Title
Inflammatory Markers and Risk of Colorectal Cancer
Summary
Colorectal cancer (CRC) is the 3rd most common cancer in U.S. men and women. Known risk factor associations, such as an increased association with inflammatory bowel disease, and obesity, and decreased association with NSAID use, suggest a role for chronic inflammation in colorectal tumorigenesis. Inflammation can cause or promote tumors through cell proliferation, inhibition of apoptosis and other mechanisms. Studying circulating inflammatory markers could help uncover important molecular pathways that may help elucidate the role of inflammation in the etiology of colorectal cancer. Recently published nested case-control studies of inflammatory markers have revealed some significant findings, but many were underpowered and tested for only a few markers. We propose to test for 88 inflammatory markers in baseline serum samples from 794 CRC cases and 794 controls enrolled in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial or PLCO. Our objective is to evaluate the association of these inflammatory markers, individually and in aggregate, with the risk of CRC. In addition, we propose to evaluate the markers in relation to CRC risk and genetic factors among controls. If we find significant associations in this study, we will validate the most promising markers (up to 10), using samples from the Women's Health Initiative (WHI), a prospective cohort of over 161,000 women ages 50-79 focused on prevention of various diseases, including colorectal cancer, in postmenopausal women. Identifying inflammatory markers associated with CRC risk will help elucidate the mechanisms by which chronic inflammation contributes to CRC etiology as well as make a significant public health impact in terms of prevention and early detection.
Aims
We propose to test for a large panel of inflammatory markers in baseline serum samples from 794 colorectal cancer (CRC) cases and 794 controls enrolled in the screening arm of PLCO. Controls and cases will be individually-matched by time of blood draw (am/pm), age, sex, ethnicity, time from baseline to diagnosis/selection, time of day of blood draw and calendar year of entry in a 1:1 ratio. The main objectives are: 1. To evaluate the association between baseline inflammatory marker levels and risk of CRC. We will evaluate each marker individually as well as in aggregate with other markers measured. Because many of the markers are likely to be correlated, we will group markers together guided by factor analysis. 2. As a secondary aim, we will evaluate determinants of baseline inflammatory marker levels among controls. We will evaluate marker levels in relation to CRC risk factors and other factors based on the questionnaire data, including BMI, smoking, and NSAID use. We will also evaluate markers in relation to genetic polymorphisms, including inflammatory genes, based on the GWAS data.
Collaborators
Ligia Pinto (NCI-Frederick)
Mahboobeh Safaeian (DCEG)
Ruth Pfeiffer (DCEG)
Ulrike Peters (Univ. of Washington)
Sonja Berndt (DCEG)
Troy Kemp (NCI-Frederick)
Allan Hildesheim (DCEG)
Cindy Chang (NCI)
