Investigation of the relationship between prostate cancer and MSMB and NCOA4 genetic variants and protein expression.
Hum Mutat
; 34(1): 149-56, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-22887727
ABSTRACT
Two genome-wide association studies (GWAS) identified the ß-microseminoprotein (MSMB) promoter SNP, rs10993994C>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, rs7350420T>C, was associated with a 15% reduction in PC risk, but the association was not significant after adjustment for the rs10993994C>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 rs10993994C>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 rs10993994C>T and NCOA4 expression, and only moderate associations were seen between two NCOA4 SNPs, rs10761618T>C and rs7085433G>A, and NCOA4 protein expression. These data indicate that the increase in PC risk associated with rs10993994C>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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Polimorfismo de Nucleotídeo Único
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Proteínas Secretadas pela Próstata
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Coativadores de Receptor Nuclear
Tipo de estudo:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Hum Mutat
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos