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Epigenetic Variation at 8q24 and Prostate Cancer Risk

Principal Investigator
Name
Kathryn Barry
Degrees
Ph.D., M.P.H.
Institution
University of Maryland School of Medicine
Position Title
Assistant Professor
Email
About this CDAS Project
Study
PLCO (Learn more about this study)
Project ID
2012-0282
Initial CDAS Request Approval
Oct 22, 2012
Title
Epigenetic Variation at 8q24 and Prostate Cancer Risk
Summary
Chromosome 8q24 has emerged as an important region for genetic susceptibility to cancer, particularly prostate cancer. Although substantial work has been done to study the role of single nucleotide polymorphisms, little research has been conducted to explore the contribution of epigenetic variation in this region on risk. Using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we propose for the first time to evaluate the association between DNA methylation levels in the chromosome 8q24 region in peripheral blood and prostate cancer risk. We will draw our study population from non-Hispanic, Caucasian male prostate cancer case and control participants in Pegasus, who have already-extracted DNA and available genome-wide association study (GWAS) genotyping data. We will quantify DNA methylation at CpG sites in the 8q24 region using pyrosequencing, which is a high-throughput, quantitative method that has been proven to be highly reproducible and is the most sensitive approach to quantify differences in DNA methylation between individuals. As secondary aims, we propose to separately evaluate the association with prostate cancer risk for aggressive and non-aggressive cases. In addition, we propose to evaluate associations between prostate cancer susceptibility loci at 8q24 and DNA methylation in this region, as well as interactions between environmental factors thought potentially related to prostate cancer and DNA methylation at 8q24 in relation to prostate cancer risk. We anticipate that these findings will provide important insights about the role of the chromosome 8q24 region in the etiology of prostate cancer.
Aims

The primary aim of the proposed study is to evaluate the association between DNA methylation levels in the chromosome 8q24 region in peripheral blood and prostate cancer risk. The secondary aims are 1) to evaluate the association between DNA methylation levels in the chromosome 8q24 region and prostate cancer risk separately for aggressive (Gleason score greater than or equal to 8 and/or Stage III/IV) and non-aggressive cases, 2) to evaluate associations between prostate cancer susceptibility loci at 8q24 (identified from prostate cancer GWAS) and DNA methylation in this region, and 3) to evaluate interactions between environmental factors thought potentially related to prostate cancer risk (e.g. dietary factors) and DNA methylation at 8q24 in relation to prostate cancer risk.

Collaborators

Laufey Amundadottir (DCEG)
Kathryn Barry (University of Maryland School of Medicine)
Joshua Sampson (DCEG)
Sonja Berndt (DCEG)
Meredith Yeager (DCEG)
Lee Moore (DCEG)
Søren Bentzen (University of Maryland School of Medicine)
Yuji Zhang (University of Maryland School of Medicine)

Approved Addenda This project has one or more approved addenda.
  • Update affiliation and modify original request for pre-diagnostic blood samples for prostate cancer cases and controls in PLCO (reduce number of subjects and amount of DNA requested)
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