Smoking related risk involved in individuals carrying genetic variants of CYP1A1 gene in head and neck cancer (original) (raw)
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American Journal of Hematology, 2009
We investigated variation in GSTs and CYPs and smoking in a population-based case-control study of NHL including 1,115 women. Although risk of NHL was not altered by variant polymorphisms in GSTs or CYPs, it was significantly changed for DLBCL when considered in conjunction with smoking behavior, though only in non-smokers. An increased risk of DLBCL in non-smokers was associated with the variant G allele for GSTP1 (OR=1.6, 95%CI: 1.0-2.3) and CYP1A1 (OR=2.4; 95%CI: 1.0-5.7), but a decreased risk for the variant G allele for CYP1B1 (OR=0.6, 95%CI: 0.4-1.0). Our results confer support investigation of the gene-environment interaction in a larger study population of DLBCL.
GST genotypes in head and neck cancer patients and its clinical implications
2008
Polymorphisms of carcinogen-metabolizing enzymes, known to be involved in metabolism of carcinogens found in tobacco smoke, are relatively common in most populations. Cigarette and bidi smoking has been demonstrated to increase the risk of head and neck cancers in our study group. This study evaluated the risk of head and neck cancers (HNC) in relation to two deletion polymorphisms of the glutathione S-transferase family GST M1 and GST T1. We found that the null GST M1 and GST T1 genotypes were associated with an increased risk of developing head and neck cancers. We found smokers, with null genotypes of GST M1 (68.3%) and GST T1 (57.5%) were at a significantly higher risk of head and neck cancers. It is possible that the decreased activity of GST affects various functions like the mechanisms of DNA damage, including those mediated by tobacco and oxidative stress. The present study investigated whether homozygous gene deletions of GST M1 and GST T1 increases the incidence of head an...
Journal of the Egyptian National Cancer Institute, 2006
Heterogeneity in patient's response to chemotherapy is consistently observed across populations. Pharmacogenomics, the study of inherited differences in drug disposition and effects, is emerging as a tool to predict efficacy and toxicity of drugs. Glutathione S-transferases (GST) are involved in the metabolism and detoxification of environmental carcinogens and some classes of chemotherapeutics. Polymorphism of GSTM1 and GSTT1, in the form of homozygous deletion, is encountered in varying frequencies in normal population. It has been associated with altered response and toxicity from cytotoxic chemotherapy. In this study, we investigated the impact of these polymorphisms on response and side effects of chemotherapy in adult acute myeloid leukaemia (AML) patients. Correlations between these genetic polymorphisms and other prognostic factors were also investigated.
Middle East Journal of Cancer, 2020
Background: Acute myeloid leukemia (AML) may originate from the combination of genetic susceptibility factors and environmental exposure. The aim of this study was to investigate the association of GSTM1 and GSTT1 null genotypes and CYP1A1*2A allele with susceptibility to AML in an Iranian population. Method: In this case-control study, 200 patients with AML and 200 normal individuals as controls were included. GSTM1 and GSTT1 null genotypes were amplified using multiplex PCR and CYP1A1*2A polymorphisms were genotyped by PCR-RFLP. Result: The frequency of GSTM1 null genotype was significantly higher in the control group compared to the case group. The frequency of GSST1 null genotype was significantly lower in the controls. No association was observed between the studied CYP1A1*2A variant and the risk of acute myeloid leukemia. The combination of GSTT1 null genotype and CYP1A1 *2A AA and AC alleles further increased the risk of AML. Conclusion: GSTT1 null genotype can increase the r...
Environmental Health Perspectives, 1992
Cytosolic glutathione S-transferases (GSTs) are a supergene family of dimeric enzymes capable of detoxifying a number of carcinogenic electrophiles. Of the numerous components of tobacco smoke, the polycyclic aromatic hydrocarbons appear to be the principal compounds that yield substrates for these enzymes, GSTM1-1 being effective with those PAH derivatives so far studied; however, the gene locus for GSTM1 is polymorphic, containing two well-characterized expressing genes and a null allele. Use of cDNA for GSTM1-1 or appropriate fragments of genomic clones as probes in Southern blots indicated that the null allele is due to the absence of GSTMI. In preliminary experiments, described here, with lung tissue from smokers, levels of 32P-postlabeled nuclease P1-enhanced DNA adducts were inversely correlated with levels of antigen cross-reacting with antibody to GSTM1-1, suggesting that initiation depends on the expression of GSTM1-1. Since similar quantities of DNA adducts and GSTM1-1 activity have been shown to occur in bronchial and peripheral lung, however, the development of malignancy, which is usually in the bronchial region, presumably depends on additional factors that bring about promotion and progression, which are not necessarily affected by GSTMI expression. Two epidemiological studies have been carried out in which a possible correlation between the absence of GSTMI and lung cancer incidence is considered. In the first, involving a U.S. population sample, smokers with and without lung cancer were phenotyped, and a highly significant correlation between the absence of GSTM1-1 activity and adenocarcinoma of the lung was observed. In the second, involving genotyping of a British population, the correlation between the homozygous GSTMI null genotype and lung cancer was much less significant and concerned squamous-cell carcinoma.
Blood, 2002
Interindividual differences in susceptibility to hematologic malignancies may be mediated in part through polymorphic variability in the bioactivation and detoxification of carcinogens. The glutathione S–transferases (GSTs) have been implicated as susceptibility genes in this context for a number of cancers. The aim of this study was to examine whether polymorphic variation in GSTs confers susceptibility to chronic lymphocytic leukemia (CLL). GSTM1, GSTT1, andGSTP1 genotypes were determined in 138 patients and 280 healthy individuals. The frequency of both GSTM1 andGSTT1 null genotypes and the GSTP1-Ile allele was higher in cases than in controls. There was evidence of a trend in increasing risk with the number of putative “high-risk” alleles of the GST family carried (P = .04). The risk of CLL associated with possession of all 3 “high-risk” genotypes was increased 2.8-fold (OR = 2.8, 95% confidence interval: 1.1-6.9). Our findings suggest that heritable GST status may influence the...