title: Association of glutathione S-transferase, EPHX, and p53 codon 72 gene polymorphisms with adult acute myeloid leukemia.
abstract: Polymorphisms in genes encoding detoxification enzymes have been suggested as susceptibility factors for many solid tumors. However, their association with hematological malignancies is controversial. A case-control study was done to determine the association between glutathione S-transferase M1 (GSTM1), GSTT1, GSTP1, EPHX1, and p53 codon 72 polymorphisms as risk factors in 120 adult acute myeloid leukemia (AML) cases and 202 healthy controls by polymerase chain reaction-restriction fragment length polymorphism techniques. Data were analyzed using χ(2) and conditional logistic regression model. None of the polymorphisms studied alone was associated with increased risk for AML. However, the frequency of GSTT1 null genotype was higher among controls (28.7%) than AML cases (21.6%), which showed a protective effect of the null genotype (odds ratio = 0.58, 95% confidence interval: 0.33-1.05, p = 0.07). In a combined analysis, both EPHX1 (His113His) and GSTP1 (Ile/Val) genes imparted a fourfold risk for adult AML but did not reach statistical significance (odds ratio = 4.22, 95% confidence interval: 0.992-17.99, p = 0.05). These findings suggest that the etiology of adult AML cannot be explained by polymorphism at a single locus, perhaps because of complexity involved in the metabolism of diverse xenobiotic compounds, and therefore, multiple gene-gene interactions should be investigated to predict the risk of AML.
authors: Institute of Pathology (Indian Council of Medical Research), Safdarjung Hospital Campus, New Delhi, India.
authors: Pradeep Singh
authors: PS
authors: Chauhan
authors: Rakhshan
authors: R
authors: Ihsan
authors: Dhirendra Singh
authors: DS
authors: Yadav
authors: Ashwani Kumar
authors: AK
authors: Mishra
authors: Bharat
authors: B
authors: Bhushan
authors: Abha
authors: A
authors: Soni
authors: Mishi
authors: M
authors: Kaushal
authors: Thoudam Regina
authors: TR
authors: Devi
authors: Sumita
authors: S
authors: Saluja
authors: Dipendra Kumar
authors: DK
authors: Gupta
authors: Vishakha
authors: V
authors: Mittal
authors: Sunita
authors: S
authors: Saxena
authors: Sujala
authors: S
authors: Kapur
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism; D055815:Young Adult
chemical_list: D003062:Codon; D016159:Tumor Suppressor Protein p53; D015262:Xenobiotics; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human