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The GSTM1 and GSTT1 genetic polymorphisms and susceptibility to acute lymphoblastic leukemia in children from north Portugal

Leukemia volume 16, pages 1565–1567 (2002)Cite this article

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer accounting for approximately 25–30% of all childhood malignancies.1,2 The origin of this disease can be explained by a combination of genetic and environmental factors, and therefore, like many other cancers, it is considered a complex disease, caused by the ‘carcinogenetic’ effect of the environment modified by a series of genes. Many of these genes tend to occur in allelic forms representing functional polymorphisms partially explaining inter-individual variability in cancer susceptibility.1 However, chemical carcinogens are not reactive per se: they require metabolic activation before interacting with genetic material that may lead to mutations and eventually the initiation of cancer. The glutathione S-transferase mu-1 (GSTM1) and glutathione S-transferase theta-1 (GSTT1) are phase II enzymes that have the ability to detoxify numerous electrophilic compounds including the activated carcinogens.1 Both GSTM1 and GSTT1 exhibit genetic polymorphism in populations with a large percentage of individuals displaying a homozygous deletion of the structural genes. Moreover, an increased frequency of GSTT1 and GSTM1 null genotypes (either in individual or combined status) has been associated with several malignancies.

Particularly concerning ALL, the studies until now performed besides being very scarce, have reported contradictory results for associations between GSTM1 and GSTT1 and cancer predisposition. For instance, Krajinovic et al3 analyzing a case-control study that involved a white population of Canadians with French origin, reported a significant association between the presence of the GSTM1 null genotype and an increased risk of ALL. For GSTT1, the authors have not detected any apparent role in the etiology of ALL. However, in a previous study, Chen et al2 have found that only the double null genotype for GSTM1 and GSTT1 was significantly more frequent among a sample of black children with ALL from USA, although failing to show a similar association among the white children analyzed. The discrepancies can be partially explained as the result of interpopulational differences in genetic backgrounds of susceptibility and/or of geographical differences in environmental exposure to carcinogens.2,3 Therefore, extensive population-specific studies are needed.

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Acknowledgements

This work was partially supported by grant PRAXIS XXI/BD/13865/97 from Fundação para a Ciência e a Tecnologia, by Comissão de Fomento da Investigação em Cuidados de Saúde. Ministério da Saúde PI No. 126/01. And IPATIMUP by Programa Operacional Ciência, Tecnologia e Inovação (POCTI), Quadro Comunitário de Apoio III.

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Authors and Affiliations

  1. IPATIMUP, Porto, Portugal

    S Alves, A Amorim & MJ Prata

  2. Faculdade de Ciências da Universidade do Porto, Porto, Portugal

    S Alves, A Amorim & MJ Prata

  3. Serviço de Hematologia Pediátrica, Hospital Geral S João, Porto, Portugal

    F Ferreira & L Norton

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  1. S Alves
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Alves, S., Amorim, A., Ferreira, F. et al. The GSTM1 and GSTT1 genetic polymorphisms and susceptibility to acute lymphoblastic leukemia in children from north Portugal. Leukemia 16, 1565–1567 (2002). https://doi.org/10.1038/sj.leu.2402543

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