Genetic polymorphism of CYP1A1, CYP2D6, GSTM1 and GSTT1 and susceptibility to acute lymphoblastic leukaemia in Indian children
- 25 May 2004
- journal article
- research article
- Published by Wiley in Pediatric Blood & Cancer
- Vol. 43 (5), 560-567
- https://doi.org/10.1002/pbc.20074
Abstract
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.Keywords
This publication has 52 references indexed in Scilit:
- Increased risk for acute myeloid leukaemia in individuals with glutathione S -transferase mu 1 (GSTM1) and theta 1 (GSTT1) gene defectsEuropean Journal of Haematology, 2001
- Genetic variability in susceptibility and response to toxicantsToxicology Letters, 2001
- Genetic polymorphism of CYP2D6 in a Keralite (South India) populationBritish Journal of Clinical Pharmacology, 2000
- Genetic polymorphism of CYP2D6, GSTM1 and NAT2 and susceptibility to haematological neoplasiasCarcinogenesis: Integrative Cancer Research, 1999
- Application of biologic markers to studies of environmental risks in children and the developing fetus.Environmental Health Perspectives, 1995
- Relationship between genotype and function of the human CYP1A1 geneJournal of Toxicology and Environmental Health, 1993
- High Susceptibility to Lung Cancer Analyzed in Terms of Combined Genotypes of P450IA1 and Mu‐class Glutathione S‐Transferase GenesJapanese Journal of Cancer Research, 1992
- The Human Hepatic Cytochromes P450 Involved in Drug MetabolismCritical Reviews in Toxicology, 1992
- Identification of the primary gene defect at the cytochrome P450 CYP2D locusNature, 1990
- Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P45 0IA1 geneFEBS Letters, 1990