Identification of Differentially Methylated Genes in Normal Prostate Tissues from African American and Caucasian Men

Abstract

Purpose: Aberrant DNA methylation changes are common somatic alterations in prostate carcinogenesis. We examined the methylation status of six genes in prostate tissue specimens from African American (AA) and Caucasian (Cau) males.Experimental Design: We used pyrosequencing to quantitatively measure the methylation status of GSTP1, AR, RARβ2, SPARC, TIMP3, and NKX2-5. Real-time PCR was used to determine gene expression, and gene reactivation was analyzed by 5-aza-2′-deoxycytidine and/or trichostatin A treatment.Results: Statistical analysis showed significantly higher methylation in the prostate cancer tissue samples in comparison with matched normal samples for GSTP1 (P = 0.0001 for AA; P = 0.0008 for Cau), RARβ2 (P < 0.001 for AA and Cau), SPARC (P < 0.0001 for AA and Cau), TIMP3 (P < 0.0001 for AA and Cau), and NKX2-5 (P < 0.0001 for AA; P = 0.003 for Cau). Overall, we observed significant differences (P < 0.05) in the methylation level for all genes, except GSTP1, in the AA samples in comparison with the Cau samples. Furthermore, regression analysis revealed significantly higher methylation for NKX2-5 (P = 0.008) and TIMP3 (P = 0.039) in normal prostate tissue samples from AA in comparison with Cau, and a statistically significant association of methylation with age for NKX2-5 (P = 0.03) after adjusting for race.Conclusion: Our findings show higher methylation of several genes in prostate

Validation of a Real-Time PCR–Based Qualitative Assay for the Detection of Methylated SEPT9 DNA in Human Plasma

“…Additional logistic regression analysis of our data suggests that the difference in specificity can be correlated, in part, with subject age and ethnicity. This is intriguing, as it has been previously reported that DNA methylation patterns for some genes depend on both subject age and ethnicity (33 ).…”

Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone

“…The studies that involved unbiased screening by gene expression analysis have shown SPARC expression to be correlated with high-grade, androgen-resistant, and metastatic disease. In addition, SPARC was shown previously to attract prostate cancer cells into bone by promoting a migratory and invasive phenotype (39 -42 (48) have shown that SPARC is silenced by promoter methylation in African-American patients who often develop aggressive prostate cancer with 2-fold higher mortality rate than Caucasian American patients (48). The apparent disagreement between these studies may be due to multiple factors, including expression profiling of the primary tumor, batch variability, and lack of clinical data for the site of metastasis.…”

Interracial differences in prostate cancer progression among patients from the United States, China and Japan

“…9 These results are supported by differences in the specific methylation of genes such as GSTP1, AR, RAR beta2, SPARC, TIMP3 and NKX2-5 in which higher methylation was found in African-Americans than in Caucasian-Americans. 10 The methylation differences found in adulthood could potentially be contributed by neonatal imprinting, as demonstrated in our early studies where we showed that both the growth of sex steroid-sensitive organs and their steroidmetabolizing enzymes in the target organs were affected by prior exposure of animals to testosterone or 17-b-estradiol during the neonatal period. [11][12][13] In addition to the report cited above characterizing racial/ethnic differences in prostate cancer among AfricanAmericans, Caucasian-Americans, Chinese and Japanese, numerous other attempts have been made to characterize the differences among Americans, Europeans, Africans and other Asian races.…”