Genetic polymorphism of CYP1A1, CYP2D6, GSTM1 and GSTT1 and susceptibility to acute lymphoblastic leukaemia in Indian children

• Published in: Pediatric Blood & Cancer Vol. 43; no. 5; pp. 560 - 567
• Main Authors: Joseph, Thomas, Kusumakumary, P., Chacko, Priya, Abraham, Annie, Radhakrishna Pillai, M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2004; Wiley
• Subjects: Adolescent; Biological and medical sciences; Biotransformation; Carcinogens - metabolism; Case-Control Studies; Child; Child, Preschool; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P-450 CYP2D6 - genetics; cytochrome P450 (CYP); Female; General aspects; Genetic Predisposition to Disease; glutathione S-transferase (GST); Glutathione Transferase - genetics; Humans; India - ethnology; Infant; Infant, Newborn; Male; Medical sciences; Odds Ratio; polymorphisms; Precursor Cell Lymphoblastic Leukemia-Lymphoma - ethnology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - etiology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Tumors; Xenobiotics - metabolism; India; Human; Pediatrics; Genetic variability; Enzyme; Transferases; Acute; Cytochrome P450; Genotype; Malignant hemopathy; glutathione S-transferase (GST); polymorphisms; Cancerology; Glutathione transferase; Lymphoproliferative syndrome; Indian; Acute lymphocytic leukemia; Child; cytochrome P450 (CYP); Polymorphism
• ISSN: 1545-5009; 1545-5017; 1096-911X
• DOI: 10.1002/pbc.20074

Background Biotransformation plays a crucial role in carcinogen activity and many genetic polymorphisms in xenobiotic metabolising enzymes have been associated with an increased risk of cancer. Such polymorphisms can lead to considerable variation in the activities of these enzymes, which are crucial in carcinogen and drug metabolism. These variations could play a role in the risk of developing paediatric acute lymphoblastic leukaemia (ALL) by their varying action on environmental carcinogens. Procedure The present study looked for two polymorphisms (m1 and m2) in the CYP1A1, CYP2D6*4 genes and deletions of the glutathione S‐transferases (GSTM1 and GSTT1) in 118 paediatric ALL patients and 118 age matched control children. The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to study gene polymorphisms. Results In children with ALL, CYP1A1 m1 polymorphism was evident in 42.4% of subjects and CYP1A1 m2 in 37.3%. These were significantly different from the results obtained for control children (20.3% for CYP1A1 m1 and 19.5% for m2). Subjects with CYP1A1 m1 homozygous variant had a sixfold risk and CYP1A1 m2 a fourfold risk. In contrast, CYP2D6*4 was more prevalent in the controls than in the cases. Subjects with GSTM1 deletions had increased risk of ALL (OR = 2.1, P = 0.009). The odds ratios for both CYP1A1 m1 and m2 homozygous polymorphisms being associated with childhood ALL was 5.67 (95% CI = 2.11–15.27). The odds ratios for both GSTM1 and GSTT1 deletions being associated with ALL was 2.78 (95% CI = 0.67–11.56). Conclusions These results suggest that genetic polymorphisms of xenobiotic metabolising enzymes appear to influence susceptibility to childhood ALL. © 2004 Wiley‐Liss, Inc.