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Inflammatory Markers and Subsequent Risk of Prostate Cancer

Principal Investigator
Name
Ann Hsing
Degrees
-
Institution
NCI, DCEG, HREB
Position Title
-
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2010-0034
Initial CDAS Request Approval
Jan 20, 2011
Title
Inflammatory Markers and Subsequent Risk of Prostate Cancer
Summary
Accumulating evidence suggest a possible link between inflammation and prostate cancer risk. Within the PLCO, aspirin use, higher serum C-peptide levels, antibodies to sexually transmitted diseases, and certain variants in inflammation-related genes were associated with prostate cancer risk. Our preliminary analysis of CGEMS data also showed potential joint effects of serum androgens and inflammation genes variants on prostate cancer risk, providing further evidence for a relationship between inflammation and prostate cancer. However, few epidemiologic studies have measured circulating inflammatory markers levels due largely to the lack of reliable serum-based assays. Recent methodological work using PLCO biospecimens show that multiplexed cytokine assays using 0.4 ml of serum can measure over 50 cytokines with good reproducibility, suggesting that it is feasible to use these panels to assess the role of inflammation in prostate cancer etiology. Therefore, we propose a nested case-control study of 1,200 prostate cancer cases and 1,200 controls within the PLCO to measure a panel of 60-65 inflammation markers and test the hypothesis that men with higher circulating levels of pro-inflammatory and/or lower levels of anti-inflammatory markers have increased prostate cancer risk. Secondary aims of the proposed study include determining whether: 1) prostate cancer risk due to circulating inflammatory markers differs by inflammation-related gene variants; and 2) serum cytokines levels correlate with variants of inflammation-related genes. Results from this study will provide a more comprehensive characterization of inflammatory biomarkers involved in prostate carcinogenesis and help elucidate inflammation's role in prostate cancer etiology.
Aims

Primary aim: To evaluate the association of prediagnostic serum levels of 60-65 markers, including cytokines, chemokines, growth factors, and angiogenesis markers, with incident prostate cancer. We plan to measure serum levels of 60-65 markers related to inflammation, including pro- and anti-inflammatory cytokines, chemokines, growth factors, and angiogenesis markers (see Table 1), using a bead-based multiplex assay in a nested case-control study of 1,200 cases and 1,200 controls. We hypothesize that higher levels of pro-inflammatory markers and lower levels of anti-inflammatory markers are associated with an increased risk of prostate cancer. Secondary Aims: To evaluate the effects of SNPs in inflammation-related genes on a varied cytokine background on prostate cancer risk. We will seek approval from the DCEG Genotyping Review Committee (GRC) to gain access to available genotyping data on inflammation-related genes (9,932 tag SNPs representing 758 inflammation-related genes; Table 2) as part of a CGEMS Value-added Study after receiving approval from EEMS for the serum cytokine component. We hypothesize that the effect of SNPs in inflammation-related genes on prostate cancer risk may vary depending on the background of circulating inflammatory markers. To determine the correlation between serum levels of cytokines and variants of inflammation-related genes (already genotyped in CGEMS).

Collaborators

Amanda Black (DCEG)
Anil Chaturvedi (DCEG)
Lisa Chu (DCEG/NCI Contractor)
Wen-Yi Huang (DCEG)
Ligia Pinto (SAIC Frederick)
Mark Purdue (DCEG)
Philip Rosenberg (DCEG)
Kai Yu (DCEG)

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