Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review.

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10-20%) than among Asians (50-60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.

Legal issues of addiction assessment: the experience with hair testing in Greece.

The purpose of this paper is to present Greek law and legislation for crimes and felonies regarding drugs of abuse and the interpretation of hair testing results with respect to Greek law. Details (such as the process, the decision and the competence of the Court, the police record, the indictment, the expert reports, the defendant's individuality, the crimes and the penal confrontal and many others) from legal cases related to toxicomany and its judicial verification were collected and analysed. Laboratory data of cases concerning the laboratory evaluation of toxicomany in addicts and also occasionally the legal course of cases with addict defendants are presented. In four representative cases segmental hair analysis proved that, for as long as the individuals were imprisoned, findings with drug substances corresponding to that period were lesser or practically absent compared with samples corresponding to the time out of prison, which showed increased drug abuse. Hair analysis provides information on chronic exposure rather than acute poisoning. Its detection window varies from some days to months or even years. The procedure that the law lays down in many cases is insufficient and in most cases impossible to abide by. When the medical examiner is not able to decide if the claim of toxicomany is real, segmental hair analysis may be the only way to prove it. In other cases where the medical examiner is able to diagnose the addiction, a segmental hair analysis is necessary because it can show long-term drug abuse.

Monitoring of pesticide residues in fresh peaches produced under conventional and integrated crop management cultivation.

The frequency and severity of crop protection product (pesticide) contamination of peaches grown conventionally were compared with those of peaches grown by integrated crop management (ICM). The peach samples (n = 150) were collected preharvest (June-August 2001) from both conventional (n = 55) and ICM (n = 95) cultivations from the Pella and Imathia districts of Macedonia, Northern Greece. The residue levels of selected insecticides, fungicides and acaricides in peach samples were determined by gas chromatography-mass spectrometry following solid-phase extraction. The concentrations of all detected pesticides were lower than the maximum residue limits (MRLs) in all peach samples grown with the ICM system (p<0.001). However, chlorpyrifos residues at levels higher than the MRLs were detected in four peach samples (i.e. 7% of the total samples) grown by the conventional system. Comparing the results for both cultivation methods with the reported average percentage (3.6%) of fruit samples with pesticide residues above the MRLs (European Union report for Greece in 2001), it was concluded that the initial implementation of the ICM in Greece was successful. The present study indicates that ICM cultivation has a higher efficiency in terms of product safety and quality. Furthermore, the results suggest that the application of conventional cultivation requires continuous monitoring of various crop protection product levels.

Genetic polymorphisms and transcriptional pattern analysis of CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes in breast cancer.

In order to detect the contribution of cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), glutathione S-transferases M1 (GSTM1), P1 (GSTP1), and T1 (GSTT1) genes in breast cancer, genetic analysis was performed, as well as transcriptional analysis in sporadic primary tumours and corresponding adjacent normal tissues from the same patient. CYP1A1 3'-untranslated region (3'-UTR) termed as m1 (MspI) polymorphism and the null(-) deletions of both GSTM1 and GSTT1 genes were examined in genomic DNA from blood samples of 207 female breast cancer patients and 171 age and sex matched controls. The frequencies of the m1 genotype of the CYP1A1 gene in cases and controls were 0.13 and 0.15, while the frequencies of homozygotes with GSTM1(-) were 0.52, in each, and for homozygotes with GSTT1(-) were 0.14 and 0.10, respectively. Statistical analysis of these genotypes in combinations did not reveal any significant difference between the breast cancer population and the control group. Expression of mRNA levels of CYP1A1, GSTM1, GSTP1, GSTT1 and AhR genes in 31 breast cancer patients, revealed inter-individual variation in an independent manner to patient age, genotype, or tumour stage. Eighty-seven percent of the tumour specimens tested were deregulated, compared to their normal counterparts, in at least one locus. Up-regulation of CYP1A1 was observed only when one of the GSTM1 or GSTP1 was down-regulated while the other remained constant. Genotyping analysis did not show any correlation to breast cancer risk. However, RT-PCR analysis provided evidence that CYP1A1, AhR, GSTM1, GSTP1 and GSTT1 genes are frequently deregulated in breast cancer and could be used as molecular biomarkers for better clinical management of such patients, with respect to chemotherapy.