Polymorphisms of Glutathione S-Transferase Mu1 <i>(GSTM1)</i> and Theta1 <i>(GSTT1)</i> Genes in Multiple Myeloma

Polymorphisms of VEGF, GSTM1 and GSTT1 genes in multiple myeloma risk

“…The genes encoding these enzymes, GSTM1 and the GSTT1, are polymorphic and may be homozygous null in 10-60% of individuals from different populations, resulting in a lack of expression of the proteins [7]. The GSTM1 deletion was previously associated with MM progression [8,9] and MM risk [10], possibly due to a lack of carcinogen inactivation, but no influence of other GST genotypes for risk of the disease was seen [11].…”

“…The genes encoding these enzymes, GSTM1 and the GSTT1, are polymorphic and may be homozygous null in 10-60% of individuals from different populations, resulting in a lack of expression of the proteins [7]. The GSTM1 deletion was previously associated with MM progression [8,9] and MM risk [10], possibly due to a lack of carcinogen inactivation, but no influence of other GST genotypes for risk of the disease was seen [11].The GSTs can also induce AG via regulation of the hypoxia-inducible factor-1a (HIF-1a), a transcription factor that regulates VEGF transcription in response to changes in the availability of oxygen [12,13]. The GSTM1 [14] and the GSTT1 [15] genes were linked to a high angiogenic phenotype in breast tumours compared with the respective null genotypes, but their roles on AG in MM are unknown.Cancer is the second-leading cause of death in southeastern Brazil, and MM induces death in elderly individuals [16].…”

Familial multiple myeloma. Two more families

“…However, the literature discussing the relationship of enzyme polymorphism and disease development is controversial. In cohorts of 58 and of 86 MM patients there was no difference in the polymorphism of these detoxifying enzymes in comparison to the average population [9,10]. In contrast, according to the study of Lincz et al there was a higher incidence (22 of 68) of GSTT1 null genotype in cases of multiple myeloma than in controls (29 of 176) [11].…”

Genetics and molecular epidemiology of multiple myeloma: The rationale for the IMMEnSE consortium (Review)

“…Glutathione-S-transferases (GSTs) conjugate phase I activated metabolites to favour their excretion from the organism. Polymorphisms in the GSTM1, GSTT1 and GSTP1 loci have been investigated in several case-control studies with weak evidence of association (102)(103)(104)(105). Although not confirmed in other studies, Lincz et al showed an association between the GSTT1 null genotype and an increased MM risk.…”