Polymorphism

Factors that regulate the metabolism of environmental and occupational carcinogens may be critical in modifying MM risks in different individuals. The human xenobiotic metabolizing system is responsible for completing the detoxification of procarcinogens. The system comprises two classes of enzymes: phase 1 cytochrome P450 and phase 2 enzymes, including glutathione S-transferases (GST Ml and GST T1), paraoxonase 1 (PON1), and N-acetyltransferases (NAT) 1 and 2. Interindividual variability in the xeno-biotic enzyme system can predispose certain racial groups to the carcinogenic effects of certain chemicals. In a case-control study using peripheral blood or bone marrow biopsy specimens from 90 Caucasian individuals and a control group consisting of 205 healthy Caucasian volunteer bone marrow donors, there was a significant increase in incidences of the GST T1 null; PON1 BB and NAT2 slow acetylation genotypes in MM cases compared with controls. Multivariate analysis revealed that GST T1 null was the most significant risk factor for MM. Interestingly the GST T1 enzyme has been identified as essential for benzene biodegradation. African Americans have an increased frequency of GST T1 null genotypes; this may explain the high incidence of MM. The study presents the evidence that inherited polymorphisms in genes are responsible for metabolizing carcinogens that can affect the individual risk for developing hematologic diseases.160

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