Communicated by Stephen J. Chanock
Investigation of the Relationship Between Prostate Cancer and MSMB and NCOA4 Genetic Variants and Protein Expression
Article first published online: 4 OCT 2012
© 2012 Wiley Periodicals, Inc.
Volume 34, Issue 1, pages 149–156, January 2013
How to Cite
FitzGerald, L. M., Zhang, X., Kolb, S., Kwon, E. M., Liew, Y. C., Hurtado-Coll, A., Knudsen, B. S., Ostrander, E. A. and Stanford, J. L. (2013), Investigation of the Relationship Between Prostate Cancer and MSMB and NCOA4 Genetic Variants and Protein Expression. Hum. Mutat., 34: 149–156. doi: 10.1002/humu.22176
Contract grant sponsors: National Cancer Institute, National Institutes of Health (RO1 CA056678, R01 CA092579, R03 CA121871, R03 CA137799 [to J.L.S.], P50 CA097186 [to J.L.S. and L.M.F.]); Fred Hutchinson Cancer Research Center; Intramural Program of the National Human Genome Research Institute.
- Issue published online: 20 DEC 2012
- Article first published online: 4 OCT 2012
- Accepted manuscript online: 7 AUG 2012 04:01PM EST
- Manuscript Accepted: 19 JUL 2012
- Manuscript Received: 22 APR 2012
- National Cancer Institute
- National Institutes of Health. Grant Numbers: RO1 CA056678, R01 CA092579, R03 CA121871, R03 CA137799
- Fred Hutchinson Cancer Research Center
- Intramural Program of the National Human Genome Research Institute
- prostate cancer;
Two genome-wide association studies (GWAS) identified the β-microseminoprotein (MSMB) promoter SNP, rs10993994:C>T, as significantly associated with prostate cancer (PC) risk. Follow-up studies demonstrate that the variant allele directly affects expression of the MSMB-encoded protein, PSP94, and also suggest that it affects mRNA expression levels of an adjacent gene, NCOA4, which is involved in androgen receptor transactivation. In a population-based study of 1,323 cases and 1,268 age-matched controls, we found the NCOA4 SNP, rs7350420:T>C, was associated with a 15% reduction in PC risk, but the association was not significant after adjustment for the rs10993994:C>T genotype. Tumor tissue microarrays of 519 radical prostatectomy patients were used to measure PSP94 and NCOA4 protein expression. Taken together, these data confirm that the rs10993994:C>T variant allele is associated with decreased PSP94 expression, and the association is stronger in tumor compared to normal prostate tissue. No association was observed between rs10993994:C>T and NCOA4 expression, and only moderate associations were seen between two NCOA4 SNPs, rs10761618:T>C and rs7085433:G>A, and NCOA4 protein expression. These data indicate that the increase in PC risk associated with rs10993994:C>T is likely mediated by the variant's effect on PSP94 expression; however, this effect does not extend to NCOA4 in the data presented here.