-
- Bernard Kwabi-Addo
- 1Department of Pathology, Baylor College of Medicine,
-
- Woonbok Chung
- 3Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
-
- Lanlan Shen
- 3Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
-
- Michael Ittmann
- 1Department of Pathology, Baylor College of Medicine,
-
- Thomas Wheeler
- 1Department of Pathology, Baylor College of Medicine,
-
- Jaroslav Jelinek
- 3Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
-
- Jean-Pierre J. Issa
- 3Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
説明
<jats:title>Abstract</jats:title> <jats:p>Purpose: Prostate cancer is a leading cause of cancer death among the aging male population but the mechanism underlying this association is unclear. Aberrant methylation of promoter CpG islands is associated with silencing of genes and age-dependent methylation of several genes has been proposed as a risk factor for sporadic cancer. We examined the extent of gene methylation in pathologically normal human prostate as a function of age.</jats:p> <jats:p>Experimental Design: We used pyrosequencing to quantitatively analyze the methylation status of nine CpG islands in normal prostate tissue DNA from 45 organ donors and 45 patients who had undergone cystoprostatectomy for bladder cancer. We also analyzed 12 pairs of matched benign and prostate cancer tissue DNA from patients with prostate cancer.</jats:p> <jats:p>Results: Linear regression analysis revealed a significant increase in promoter methylation levels correlating with age for CpG islands at RARβ2 (r = 0.4; P < 0.0001), RASSF1A (r = 0.27; P = 0.01), GSTP1 (r = 0.59; P < 0.0001), NKX2-5 (r = 0.27; P = 0.008), and ESR1 (r = 0.244; P = 0.023) in the normal prostate tissue samples studied. A calculated average methylation (z score) at all nine CpG loci analyzed in the normal prostate tissues showed a strong correlation with age (r = 0.6; P < 0.001). Comparison of the methylation level for the matched benign and prostate cancer tissues from individual patients with prostate cancer showed significantly higher methylation in the prostate cancer tissue samples for RARβ2 (P < 0.001), RASSF1A (P = 0.005), GSTP1 (P < 0.001), NKX2-5 (P = 0.003), ESR1 (P = 0.016), and CLSTN1 (P = 0.01).</jats:p> <jats:p>Conclusions: Our findings show aberrant hypermethylation as a function of age in the normal prostate tissues. Such age-related methylation may precede and predispose to full-blown malignancy.</jats:p>
収録刊行物
-
- Clinical Cancer Research
-
Clinical Cancer Research 13 (13), 3796-3802, 2007-07-01
American Association for Cancer Research (AACR)