A41
From genome-wide association studies to clinical application: MSMB as a prostate cancer biomarker
Hayley Whitaker1, Zsofia Kote-Jarai2, Anne Warren3, William Howat1, Rosalind Eeles2, David Neal1
1CRUK Cambridge Research Institute, Cambridge, UK, 2Institute of Cancer Research, Sutton, UK, 3Addenbrookes Hospital, Cambridge, UK
A small nucleotide polymorphism (SNP) in the microseminoprotein beta (MSMB) promoter has recently been identified in a genome-wide association study as increasing the risk of developing prostate cancer. MSMB is known to promote apoptosis and is suggested to negatively regulate prostate cell growth and metastasis and promote apoptosis. The location of the SNP within the promoter suggests that it may alter MSMB expression.
We have used immunohistochemistry of patient samples (n=434) to demonstrate consistent loss of MSMB with prostate cancer and PIN suggesting MSMB is an effective and robust prostate cancer biomarker. MSMB is prostate specific and could not be detected in normal or tumourigenic tissue from multiple organs. MSMB cannot be detected in urothelium, seminal vesicles or bladder. We have also developed an ELISA allowing detection and comparison of MSMB in urine, serum and plasma (n=380). Using the ELISA we have examined changes urinary MSMB with tumourigenesis and increasing Gleason grade. Work is ongoing to link expression to patient genotype and SNP status.
