CYP1B1 Polymorphism as a Risk Factor for Race-Related Prostate Cancer

Abstract

Abstract : When comparing races, the incidence and mortality rate of prostate cancer are higher in African Americans than in Caucasians and Asians. Cytochrome P450 (CYP) 1B1 converts estrogens to the 4-hydroxy-catechol-estrogens. Studies show this catechol-estrogen is mutagenic and may lead to prostate cancer. Recently, the authors showed that CYP1B1 polymorphisms present a higher risk for prostate cancer; however, studies of CYP1B1 are lacking in race-related prostate cancer. There are at least 4 polymorphisms that have been identified on the CYP1B1 gene that result in a structural change in the enzyme, and they are at the following locations: codons 48, 119, 432, and 453. The goal of this project is to investigate whether polymorphisms of the CYP1B1 gene are a risk factor for race-related prostate cancer. Two hypotheses were tested: (1) that the CYP1B1 gene is hyper-activated during malignant transformation of race-related prostate cells, and (2) that single nucleotide polymorphisms (SNPs) of the CYP1B1 gene have a higher risk for race-related prostate cancer and correlate with a hyper-activated CYP1B1 gene. The authors used 77 benign prostatic hyperplasia (BPH) and 96 prostate cancer (PC) samples from African American and Caucasian patients that were collected earlier. To test the first hypothesis, they performed immunohistochemical analysis to determine CYP1B1 protein expression in the BPH and PC samples. Preliminary results show that the CYP1B1 protein is localized to the cytoplasm of PC cells, and that the intensity of CYP1B1 staining is much higher in the PC than the BPH samples. To test the second hypothesis, single nucleotide polymorphisms (SNPs) at three codons (119, 432, and 453) of CYP1B1 were evaluated to determine if they are risk factors for race-related PC. Racial differences were observed in allele frequencies. The variants at codons 119 (P < 0.05) and 432 (P < 0.001) were greater among Blacks, whereas the 453 variant (P < 0.001) was predominant in Whites.