Get access
Advertisement

Investigation of the Relationship Between Prostate Cancer and MSMB and NCOA4 Genetic Variants and Protein Expression

Authors


  • Communicated by Stephen J. Chanock

  • 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.

Correspondence to: Janet L. Stanford, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109. E-mail: jstanfor@fhcrc.org

ABSTRACT

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.

Get access to the full text of this article

Ancillary