Association of Prostate-Specific Antigen Promoter Genotype with Clinical and Histopathologic Features of Prostate Cancer

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 17; no. 9; pp. 2451 - 2457
• Main Authors: Cramer, Scott D, Sun, Jielin, Zheng, S Lilly, Xu, Jianfeng, Peehl, Donna M
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2008
• Subjects: Alleles; Biological and medical sciences; Biomarkers, Tumor - genetics; Chi-Square Distribution; Genotype; Gleason grade; Humans; Logistic Models; Male; Medical sciences; Nephrology. Urinary tract diseases; Polymorphism, Single Nucleotide; promoter; Promoter Regions, Genetic - genetics; prostate-specific antigen; Prostate-Specific Antigen - blood; Prostate-Specific Antigen - genetics; Prostatectomy; Prostatic Neoplasms - blood; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; Statistics, Nonparametric; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urinary system disease; Typing; Prostate disease; Clinical form; Genotype; Tumoral marker; Malignant tumor; Prostate specific antigen; Promoter; Symptomatology; Anatomic pathology; Association; Cancerology; Histopathology; Urogenital system; Male genital diseases; Prostate cancer; Prostate; Cancer
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-08-0374

The serum test for the secreted protease prostate-specific antigen (PSA) is the most widely used screening tool for prostate cancer. The PSA gene contains multiple functional and nonfunctional single nucleotide polymorphisms (SNP) in its promoter. We showed previously that the rs925013 G/A SNP, but not the rs266882 G/A SNP, was significantly associated with serum PSA in healthy men. In this study, we evaluated the association of the PSA promoter genotype with clinical data in a cohort of 1,224 men with prostate cancer. Previous work with a subset of this cohort has shown that percent high-grade (Gleason grades 4 and 5) cancer was the strongest predictor of biochemical recurrence (PSA relapse). We found a statistically significant association ( P < 0.05) of the rs925013 SNP with several clinical and histomorphologic variables. The G allele was associated with higher serum PSA at diagnosis, higher percent Gleason grade 3 cancer, and lower percent high-grade and Gleason grade 4 cancer. The rs266882 SNP was modestly associated with PSA at diagnosis in a dominant model but was not associated with cancer grade. Neither SNP was associated with biochemical recurrence. The statistically significant predictors of biochemical recurrence were tumor location in the peripheral zone [odds ratio (OR), 10.71; 95% confidence interval (95% CI), 3.15-36.49], presence of any Gleason grade 4/5 cancer (OR, 4.26; 95% CI, 1.30-14.00), presence of any intraductal cancer (OR, 1.03; 95% CI, 1.00-1.04), and serum PSA at diagnosis (OR, 2.04; 95% CI, 1.50-2.77). (Cancer Epidemiol Biomarkers Prev 2008;17(9):2451–7)