Characterization and Functional Analysis of Two Common Human Cytochrome P450 1B1 Variants

Pharmacogenetics and Regulation of Human CytochromeP450 1B1: Implications in Hormone-Mediated Tumor Metabolism and a Novel Target for Therapeutic Intervention

“…However, increased basal mRNA levels of CYP1B1 have been observed in cell culture (109), suggesting a possible role for these polymorphisms in CYP1B1-mediated carcinogenesis. Similarly, the A443G polymorphism has not been associated with the functional properties of CYP1B1 when considered outside the context of a haplotype (107,108).…”

“…The C142G and G355T polymorphisms (CYP1B1*2) are tightly linked (106) and result in amino acid substitutions (CYP1B1.2) that have not been found involved in the catalytic properties of CYP1B1 when not considered in combination with other functional alleles (107,108) and are located near the hinge region of CYP1B1 (see Fig. 1A; ref.…”

“…The corresponding protein variants are labeled as CYP1B1.5, CYP1B1.6, and CYP1B1.7. (108). However, other functionally important CYP1B1 variants, including CYP1B1.3 and CYP1B1.4, were not evaluated, and other studies have shown that both CYP1B1.3 and CYP1B1.4 are important in determining catalytic efficiency and the protein processing of CYP1B1 in both COS-1 and other cellular expression systems.…”

Ovarian Cancer Risk and Polymorphisms Involved in Estrogen Catabolism

“…If multiple polymorphisms in a single gene affect enzyme function in an epistatic fashion, such an analysis may have a relatively greater ability to identify an association with cancer risk. Prior in vitro enzyme function studies have shown differences in estrogen 4-OH rates across the CYP1B1 haplotypes with conflicting results (25,(31)(32)(33)(34) allele (SULT1A1*2) is associated with f2-fold lower enzyme activity and is less thermostable (38) (9,10,13,14).…”

Polymorphisms in the CYP1B1 gene are associated with increased risk of prostate cancer

“…Multiple functional studies report that these nonsynonymous SNPs of CYP1B1 alter enzymatic activity and catalytic specificity. However, the results have not been consistent and are difficult to compare because different variants were tested (a total of 16 combinations for four amino-acid substitutions), and different expression and assay systems were used, in each laboratory (Hanna et al, 2000;Li et al, 2000;McLellan et al, 2000;Shimada et al, 2001;Aklillu et al, 2002).…”