[show abstract][hide abstract] ABSTRACT: Codon 72 polymorphism of the tumor suppressor gene TP53 has been associated with a higher risk in the development of several types of cancer. The polymorphism results in a variant protein with either an arginine (CGC) or a proline residue (CCC). The aim of this study was to analyze the association of the TP53 codon 72 polymorphism with the risk of developing gastric cancer in a high-risk population from the central-western region of Venezuela. DNA was extracted from paraffin-embedded gastric adenocarcinoma biopsies (n=65) and endoscopic biopsies from chronic gastritis patients (n=87). TP53 codon 72 polymorphism was determined by PCR-RFLP from all samples. Patients with gastric cancer had a significantly higher frequency (P = 0.037) of the Arg allele than those with chronic gastritis. A logistic regression analysis suggested that Arg carrier individuals had a 4.6-fold higher risk (95% CI 1.0-21.3) of developing gastric cancer. An increment of the Arg/Arg genotype was observed in poor-differentiated gastric adenocarcinoma (OR: 3.1; 95% CI 1.0-9.2), and of the Arg/Pro genotype in well/moderate-differentiated adenocarcinoma samples (OR: 3.5; 95% CI 1.1-11.0), when comparing within the gastric cancer samples; and the last group also when contrasting it with chronic gastritis patients (OR: 2.4; 95% CI 1.1-5.2). The results of this study suggest that the carriage of the Arg allele could be associated with the development of gastric cancer in this Venezuelan population.
[show abstract][hide abstract] ABSTRACT: Slow drug degradation by CYP enzymes can lead to its accumulation in the body with subsequent toxic effects. CYP2D6 is involved in the metabolism of many toxicologically important drugs such as tricyclic antidepressants, commonly implicated in fatal drug poisonings. Since in human populations the gene coding for this enzyme exhibits high genetic polymorphism, they are of major pharmacogenetic importance. The aim of this work is to describe the distribution of genetic polymorphisms of CYP2D6 responsible for poor and intermediate metabolizers phenotypes in Venezuelan population and provide guidance on the importance of conducting postmortem forensic examinations to elucidate the role of genetic variation in drug intoxications. We carried out the analysis of CYP2D6*3, *4, *5, *6 and 10* alleles of 110 unrelated healthy individuals by allele-specific PCR tetra-primer. The allelic frequencies obtained for *4 (15.9%) and *10 (16.4%) in the Venezuelan population highlights the importance of CYP2D6 genotyping in cases where a high concentration of a drug metabolized by this route has been used, without suspicion of acute overdose.
Forensic Science International Genetics Supplement Series 01/2009; 2(1):483-484.
[show abstract][hide abstract] ABSTRACT: Telomeres are nucleoprotein complexes that protect the ends of eucaryotic chromosomes from degradation and recombination. In humans, telomeres measure 10-12 kbp in normal somatic cells, but they scarcely reach 1-2 kbp in tumor cells of rapid growth, due to the incomplete replication of these structures in each mitotic division. Telomeres shorten with age, which can be associated to genomic instability and to an increment of the risk of suffering from cancer. The standard method to measure the telomere length is the analysis of telomeric restriction fragments by Southern blot. However, a precise determination is not possible when the DNA is broken into small fragments or if it is scarce. In this work, a slot blot assay was adapted to quantify the relative content, instead of the length, of telomeric DNA from paraffin-embedded archival specimens of colon adenocarcinoma. The telomeric DNA content could be reproducibly measured with hardly 75 ng of highly degraded genomic DNA by chemiluminescent detection for hybridization.