ABSTRACT
To investigate the association of glutathione-S-transferase (GST) polymorphisms with the risk of acute myeloid leukemia (AML), a meta-analysis of case-control studies published between 1998 and 2009 was performed. Pooled odds ratios (ORs) were assessed using both fixed- and random-effects models. Heterogeneity across studies was calculated, and funnel plots were constructed to test for publication bias. Overall, the random-effects OR with GSTM1 null genotype, GSTP1 Val105 allele and GSTT1 null genotype were 1.30 (95% confidence intervals (CI) 1.04-1.62, p = 0.018), 1.03 (95% CI 0.80-1.33, p = 0.80) and 1.24 (95% CI 0.98-1.58, p = 0.06), respectively. Statistically, significant increased risk of AML was observed with GSTM1 while borderline significance was seen with GSTT1 null genotypes. However, fixed-effects model showed significant risk of AML in the presence of null genotypes of GSTM1 and GSTT1(p < 0.05). Significant heterogeneity was found between studies relating to GSTP1 (p = 0.162), however, no heterogeneity was seen in studies that evaluated GSTM1 (Q-value = 44; I(2) = 70.9; p-value < 0.01]; and GSTT1 (Q-value = 26.03; I(2) = 57.74; p-value < 0.01] polymorphisms. From the limited studies on the association of GSTP1 with risk of AML, the role of this gene cannot be ascertained fully. Significant association of these three genes with risk of AML must be evaluated further with respect to population, smoking, eating habits, ethnicity, and race.
Subject(s)
Glutathione S-Transferase pi/genetics , Glutathione Transferase/genetics , Leukemia, Myeloid/genetics , Neoplasm Proteins/genetics , Polymorphism, Genetic , Acute Disease , Alleles , Carcinogens/pharmacokinetics , Case-Control Studies , Confounding Factors, Epidemiologic , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Leukemia, Myeloid/enzymology , Leukemia, Myeloid/epidemiology , Models, Genetic , Odds Ratio , Risk , Selection BiasABSTRACT
INTRODUCTION: Two common polymorphisms in cytochrome P450; family 1, subfamily A, polypeptide 1 (CYP1A1); have been implicated as a risk factor of prostate cancer, but individual studies have been inconclusive or controversial. We reviewed studies on CYP1A1 polymorphisms in patients with prostate cancer. MATERIALS AND METHODS: The strategy searching in the PubMed was based on combinations of prostate cancer, CYP1A1, CYP1A1 gene polymorphism, and genetic susceptibility. The last search update was May 2008. The retrieved articles and their bibliographies of were evaluated and reviewed independently by 2 experts. We shortlisted 19 studies, of which 14 on sporadic prostate cancer were analyzed. Overall, 2573 patients with prostate cancer and 2576 controls were analyzed. RESULTS: The random effects odds ratio was 1.350 (95% confidence interval, 1.110 to 1.641; P = .003) for T/C polymorphism and 1.085 (95% confidence interval, 0.863 to 1.364; P = .49) for A/G polymorphism. The A/G polymorphism was not associated with increased risk of prostate cancer. However, the T/C polymorphism showed conflicting results in different studies, while overall, this polymorphism showed significant effects on the susceptibility to prostate cancer. There was no significant between-study heterogeneity for both polymorphisms with respect to distribution of alleles. CONCLUSION: This meta-analysis suggests that while the CYP1A1 T/C polymorphism is likely to considerably increase the risk of sporadic prostate cancer on a wide population basis, the A/G polymorphism may not influence this risk. However, the association of polymorphisms may be significant with respect to smoking history, diet habits, ethnicity, and race.
Subject(s)
Cytochrome P-450 CYP1A1/genetics , Genetic Predisposition to Disease/epidemiology , Polymorphism, Genetic , Prostatic Neoplasms/genetics , Age Distribution , Aged , Confidence Intervals , Gene Expression Regulation, Neoplastic , Humans , Incidence , Male , Middle Aged , Odds Ratio , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/physiopathology , Risk Assessment , Sensitivity and Specificity , Survival AnalysisABSTRACT
Lead is a known toxicant that has been implicated in encephalopathy in children and may affect the gastrointestinal and hematopoietic and other systems in adults. In fact, lead has been shown to compete with calcium for entry into the synaptosome and induce toxic effects. The aim of the current study was to evaluate the cytotoxic and genotoxic effects of lead by using lymphocytes from human peripheral blood in vitro. The LC50 for lead nitrate as determined by Trypan blue dye exclusion technique was found to be 3.14 mM. Chromosomal aberration frequency at sublethal doses (1/10 of LC50) as determined by examining the metaphase chromosomes (karyotyping) did not show significant aberrations except for some aneuploidy and about 2-4% gaps, breaks (3-4%), and about 5% satellite associations. However, significant DNA damage was determined by SCGE (Comet assay). The comet tail length proportionately increased with increasing lead nitrate concentration. Thus, Pb can induce single-strand DNA breaks, possibly by competing with metal binding sites.
