Association of an MBD1 variant with prostate cancer
Principal Investigator
Name
James Burmester
Degrees
-
Institution
Marshfield Clinic Research Foundation
Position Title
-
About this CDAS Project
Study
PLCO
(Learn more about this study)
Project ID
2006-0284
Initial CDAS Request Approval
Nov 21, 2006
Title
Association of an MBD1 variant with prostate cancer
Summary
This study proposes to replicate the association between rs125555, a DNA variant in methyl-CpG binding domain 1 protein (MBD1) with prostate cancer using the PLCO cohort. Our previous results demonstrated that rs125555 associates with increased risk of prostate cancer in both a familial prostate cancer cohort of affected sibs (OR=2.63, P=0.002) and a sporadic prostate cancer cohort (OR=1.9, P=0.002). This variant is located on chromosome 18q21.1 at the linkage peak in families with two or more relatives affected with prostate cancer, but not meeting the strict Hopkin's Criteria for hereditary prostate cancer. The variant is also located extremely close to the peak of loss of heterozygosity at 18q21.1 present in up to 50% of tumors. Although functional MBD1 regulates gene expression by binding to methylated DNA and repressing transcription from methylated gene promoters, analysis of the variant protein using PolyPhen predicts that the mutated protein may be non-functional. Using the PLCO prostate cancer cohort, we may be able to replicate the genetic observation already seen in two separate patient populations, definitively demonstrating that MBD1 is a prostate cancer gene.
Aims
Specific aim 1: To test rs125555 in prostate cancer cases and disease free controls and determine if the rare allele associates with prostate cancer. Specific aim 2: To analyze rs125555 alleles for association with age-at-onset, Gleason score, and tumor stage and grade to determine if the rare allele associates with early age at diagnosis or aggressive prostate cancer.
Collaborators
James Burmester (Marshfield Clinic)
Robert Greenlee (Marshfield Clinic)
Cathy McCarty (Marshfield Clinic)
Douglas Redding (Marshfield Clinic)