GSTM1 and codon 72 P53 polymorphism in multiple myeloma

Abstract

The GSTM1 and GSTT1 genes reduce the effects of exposure to cytotoxic agents. Both genes have a null variant allele in which the entire gene is absent. On the other hand, a common polymorphism of the tumour suppressor P53 gene results in either arginine (A) or proline (P) at amino-acid position 72. The A and P alleles code proteins with distinct functions in apoptosis and DNA repair and have been associated with variable risks for several cancers. However, their roles in multiple myeloma (MM) are still unknown. We tested in study whether the GSTM1, GSTT1 and P53 genotypes altered the risk for MM in Brazilian patients. Genomic DNA from 106 patients and 230 controls were analysed by polymerase chain reaction-based methods for identification of the genotypes. Similar frequencies of the GSTM1, GSTT1 and P53 genotypes were seen in patients and controls. Individuals with the distinct genotypes had similar risks for disease. In contrast, an excess of the GSTM1 null (45.1 vs 17.2%, P = 0.009), the P53 PP+AP (70.4 vs 44.8%, P = 0.041) and the GSTM1 null plus P53 PP+AP (29.6 vs 10.3%, P = 0.004) genotypes were seen in MM patients at stage III compared with those at stages I + II. Our data suggest that the GSTM1, GSTT1 and P53 genotypes do not influence the risk for MM. However, the inherited presence of the variant codon 72 P53 allele, described here for the first time, and the absence of the GSTM1 detoxification pathway, seem to act in disease progression in our country.

p53 codon 72 polymorphism and Hematological Cancer Risk: An Update Meta-Analysis

“…We also included eligible study with hand searching [31]. By searching “p53”, “polymorphism” and “lymphoma” or “myeloma”, and a hand search from references of original studies or review articles, we included another seven articles [16], [17], [32], [33], [34], [35], [36]. The genotype distributions among the controls of all studies were in agreement with Hardy-Weinberg equilibrium except for three studies [16], [33], [36](Figure 1).…”

“…The genotype distributions among the controls of all studies were in agreement with Hardy-Weinberg equilibrium except for three studies [16], [33], [36](Figure 1). As a result, a total of thirteen studies met the inclusion criteria and were identified as eligible articles with 2,711 cases and 7,356 controls, including nine studies of leukemia [15], [31], [37], [38], [39], [40], [41], [42], [43], three studies of lymphoma [17], [32], [34] and one study of myeloma [35]. The selected study characteristics were listed in Table 1.…”

“…Although the combined effects of different p53 polymorphisms have not been studied, the potential interactions between p53 Arg72Pro polymorphism and other genetic polymorphisms, including those in Murine double minute 2 ( MDM2 ), p73 , p21 and Glutathione S-transferase , which are involved in DNA damage repair, apoptosis, cell cycle control, or detoxification of xenobiotic compounds, were found in hematological malignancies [15], [34], [35], [38], [43]. We evaluated the combined effects of these polymorphisms on susceptibility to hematological malignancies, however, due to the limited studies, the data were not sufficient to conduct a meta-analysis.…”

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.…”

Genetic polymorphisms in patients with endometriosis: an analytical study in Goiânia (Central West of Brazil)

“…A survey in Campinas (Ortega et al, 2007) analyzed the genes p53 and GSTs in 106 patients with myeloma and 230 controls. The results suggest no positive correlation, but the authors realized that the polymorphism of p53 at the codon 72 combined with null-GSTM1 polymorphism increases the disease progression.…”