James Burmester

-

Marshfield Clinic Research Foundation

-

PLCO (Learn more about this study)

2006-0284

Nov 21, 2006

Association of an MBD1 variant with prostate cancer

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.