CYP17 Promoter Variant Associated with Prostate Cancer Aggressiveness in African Americans

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 10; no. 9; pp. 943 - 947
• Main Authors: KITTLES, Rick A, PANGULURI, Ramesh K, WEIDONG CHEN, MASSAC, Aisha, AHAGHOTU, Chiledum, JACKSON, Aaron, UKOLI, Flora, ADAMS-CAMPBELL, Lucile, ISAACS, William, DUNSTON, Georgia M
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2001
• Subjects: Adult; Aged; Biological and medical sciences; Black or African American; Black People - genetics; DNA Primers; Genetic Predisposition to Disease - genetics; Genetic Variation - genetics; Humans; Male; Medical sciences; Middle Aged; Neoplasm Staging; Nephrology. Urinary tract diseases; Polymerase Chain Reaction; Polymorphism, Genetic; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Steroid 17-alpha-Hydroxylase - genetics; Tumors of the urinary system; Urinary tract. Prostate gland; United States; North America; America; Human; Urinary system disease; Prostate disease; Isozyme; Transcription promoter; Cytochrome P450; Genetic variant; Negroid; Malignant tumor; Epidemiology; Risk factor; Race; Genetics; Male genital diseases; Prostate; Public health; African American
• ISSN: 1055-9965; 1538-7755

Androgens play an important role in the etiology of prostate cancer. The CYP17 gene encodes the cytochrome P450c17α enzyme, which is the rate-limiting enzyme in androgen biosynthesis. A T to C polymorphism in the 5′ promoter region has recently been associated with prostate cancer. However, contradictory data exists concerning the risk allele. To investigate further the involvement of the CYP17 variant with prostate cancer, we typed the polymorphism in three different populations and evaluated its association with prostate cancer and clinical presentation in African Americans. We genotyped the CYP17 polymorphism in Nigerian ( n = 56), European-American ( n = 74), and African-American ( n = 111) healthy male volunteers, along with African-American men affected with prostate cancer ( n = 71), using pyrosequencing. Genotype and allele frequencies did not differ significantly across the different control populations. African-American men with the CC CYP17 genotype had an increased risk of prostate cancer (odds ratio, 2.8; 95% confidence interval, 1.0–7.4) compared with those with the TT genotype. A similar trend was observed between the homozygous variant genotype in African-American prostate cancer patients and clinical presentation. The CC genotype was significantly associated with higher grade and stage of prostate cancer (odds ratio, 7.1; 95% confidence interval, 1.4–36.1). The risk did not differ significantly by family history or age. Our results suggest that the C allele of the CYP17 polymorphism is significantly associated with increased prostate cancer risk and clinically advanced disease in African Americans.