BI-RADS® fifth edition: A summary of changes.

The Breast Imaging Reporting and Data System (BI-RADS®) is a standardized system of reporting breast pathology as seen on mammogram, ultrasound, and magnetic resonance imaging. It encourages consistency between reports and facilitates clear communication between the radiologist and other physicians by providing a lexicon of descriptors, a reporting structure that relates assessment categories to management recommendations, and a framework for data collection and auditing. This article highlights the changes made to the BI-RADS® atlas 5th edition by comparison with its predecessor, provide a useful resource for a radiologist attempting to review the recent changes to the new edition, and serve as a quick reference to those who have previously become familiar with the material.

An allele-specific polymerase chain reaction method for the determination of the D85Y polymorphism in the human UDP-glucuronosyltransferase 2B15 gene in a case-control study of prostate cancer.

BACKGROUND: UDP-glucuronosyltransferase 2B15 (UGT2B15) catalyzes the inactivation of dihydrotestosterone (DHT) by forming the DHT-glucuronide and is expressed in normal and hyperplastic prostate tissue. Alterations in the activity of this enzyme could be a major contributing factor to the bioavailability of androgens in target tissue such as the prostate. METHODS: A polymorphism (D85 to Y85) has been identified in the UGT2B15 gene that results in a 50% reduction in enzyme activity. Previously, detection of the polymorphic nucleotide has required direct sequencing. We have developed and validated an allele-specific polymerase chain reaction (PCR) assay to identify the polymorphic base pair in the UGT2B15 gene. This assay was used to examine the distribution of the UGT2B15 polymorphism in a small case-control group (64 cases and 64 controls) from a prostate cancer study. RESULTS: The results of this analysis show that prostate cancer patients were significantly more likely to be homozygous for the lower activity D85 UGT2B15 allele than control individuals (41% versus 19%, respectively, odds ratio = 3.0 (95% confidence intervals 1.3-6.5)). CONCLUSIONS: These results suggest that individuals who are homozygous for the lower activity allele may be at increased risk for developing prostate cancer.

Cancer therapy and polymorphisms of cytochromes P450.

Cytochrome P450 (CYP) enzymes are important in the metabolism of some endogenous compounds, environmental and dietary xenobiotics and many drugs. Many of these enzymes have genetic polymorphisms that produce significant changes in metabolic activity, however the function of other polymorphisms is unknown. Genetic polymorphisms have important influences on variability in human pharmacokinetics, including intra-individual differences in drug toxicity, drug interactions and response to chemotherapy. Other factors that influence drug metabolism include differences in enzyme expression due to differences in age, gender, smoking status, exposure to dietary or environmental xenobiotics or co-administration of other drugs. In addition, some xenobiotics and drugs can directly inhibit or induce the activity of CYPs. All of these factors can produce differences in metabolic capacities among individuals which can produce toxicity in some patients and sub-effective dosing in others. Maximum clinical benefit will require a more complete understanding of the influence of these polymorphisms on allele function and their interaction with inducers and inhibitors of enzyme expression or activity. This effort will permit the pharmacogenetic screening of patients before the administration of drugs and result in the identification of individuals who are prone to adverse reactions or poor response, resulting in more effective individualized therapy.

Relationship of phenol sulfotransferase activity (SULT1A1) genotype to sulfotransferase phenotype in platelet cytosol.

Sulfation catalysed by human cytosolic sulfotransferases is generally considered to be a detoxification mechanism. Recently, it has been demonstrated that sulfation of heterocyclic aromatic amines by human phenol sulfotransferase (SULT1A1) can result in a DNA binding species. Therefore, sulfation capacity has the potential to influence chemical carcinogenesis in humans. To date, one genetic polymorphism (Arg213His) has been identified that is associated with reduced platelet sulfotransferase activity. In this study, data on age, race, gender, SULT1A1 genotype and platelet SULT1A1 activity were available for 279 individuals. A simple colorimetric phenotyping assay, in conjunction with genotyping, was employed to demonstrate a significant correlation (r = 0.23, P < 0.01) of SULT1A1 genotype and platelet sulfotransferase activity towards 2-naphthol, a marker substrate for this enzyme. There was also a difference in mean sulfotransferase activity based on gender (1.28 nmol/min/mg, females; 0.94 nmol/min/mg, males, P = 0.001). DNA binding studies using recombinant SULT1A1*1 and SULT1A1*2 revealed that SULT1A1*1 catalysed N-hydroxy-aminobiphenyl (N-OH-ABP) DNA adduct formation with substantially greater efficiency (5.4 versus 0.4 pmol bound/mg DNA/20 min) than the SULT1A1*2 variant. A similar pattern was observed with 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5b]pyridine (N-OH-PhIP) (4.6 versus 1.8 pmol bound/mg DNA/20 min).