Study
PLCO
(Learn more about this study)
Project ID
2008-0001
Initial CDAS Request Approval
Feb 15, 2008
Title
Genetic Variation in Epigenetic Control of Gene Function and Inflammation Pathways, and Prostate Cancer Risk
Summary
Although epigenetic abnormalities and inflammation have been independently implicated in prostate cancer and despite the evidence of crosstalk between chronic inflammation and epigenetic events, little is know about the interplay between them in prostate cancer risk. Epigenetics refers to modifications in gene expression that are controlled by heritable but potentially reversible changes in DNA methylation and/or chromatin structure. Aberrant epigenetic events, e.g., DNA hypo- and hypermethylation and altered histone acetylation have both been observed in prostate cancer, where these regulatory events affect a large number of cancer-associated genes including tumor suppressors. Genes that regulate the cellular epigenetic integrity, namely enzymes and catalysts involved in the establishing and maintaining epigenetic markers crucial for normal gene expression, have been implicated in carcinogenesis. To address the measurement challenges due to transient nature of epigenetic regulation, we propose to use common variation in epigenetic control pathways as biomarkers for variation in epigenetic integrity. Some single nucleotide polymorphisms (SNPs) within epigenetic control genes have been implicated in prostate cancer in preliminary results from the PLCO Cancer Genetic Markers of Susceptibility (CGEMS) scan (
https://caintegrator.nci.nih.gov/cgems/ or Appendix 1). The interrelationship between genetic variants in epigenetic control pathways and other inflammation markers, and prostate cancer has yet to be elucidiated in epidemiologic studies. We request the covariates and CGEMS data from the PLCO to evaluate the following specific aims:
Aims
1. To assess gene-environment interrelationship between SNPs in the epigenetic control pathways and available inflammation covariates in PLCO, specifically (i) soluble inflammation markers (serum C-peptide levels); (ii) pharmaceutical down-regulation (NSAID intakes), and susceptibility to prostate cancer. 2. To explore the interaction between genetic variation in epigenetic control pathways and inflammation pathways in prostate cancer risk. We aim to interrogate variants in 783 inflammation genes selected by the inflammation group (Sara Daugherty, Ann Hsing, Wen-Yi Huang, and Hui-Lee Wong; proposals submitted to the PLCO committee) and developed in collaboration with Drs. Hsing and Chanock.
Collaborators
Stephen Chanock (DCEG)
Richard Hayes (DCEG)
Chieh-Lin Hsieh (University of Southern California)
Ann Hsing (DCEG)
Wen-Yi Huang (DCEG)
Idan Menashe (DCEG)
Charles Rabkin (DCEG)
