Investigation of the Relationship Between Prostate Cancer and MSMB and NCOA4 Genetic Variants and Protein Expression. Issue 1 (4th October 2012)

• Record Type: Journal Article
• Authors: FitzGerald, Liesel M.; Zhang, Xiaotun; Kolb, Suzanne; Kwon, Erika M.; Liew, Ying Ching; Hurtado‐Coll, Antonio; Knudsen, Beatrice S.; Ostrander, Elaine A.; Stanford, Janet L.
• Is Part Of: Human mutation. Volume 34:Issue 1(2013:Jan.)
• Page Start: 149
• Page End: 156
• Publication Date: 2012-10-04
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22176
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>Two genome‐wide association studies (GWAS) identified the <italic>β</italic>‐<italic>microseminoprotein</italic> (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 <italic>MSMB</italic>‐encoded protein, PSP94, and also suggest that it affects mRNA expression levels of an adjacent gene, <italic>NCOA4</italic>, 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 <italic>NCOA4</italic> 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 <italic>NCOA4</italic> 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.</p> </abstract>