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

Pediatric Blood & Cancer
Thomas JosephM Radhakrishna Pillai

Abstract

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. 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. 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 G...Continue Reading

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