VEGF, VEGFR2 and GSTM1 polymorphisms in outcome of multiple myeloma patients in the thalidomide era

Background

Angiogenesis (AG) abnormalities are crucial in pathogenesis of multiple myeloma (MM), and give support to treat patients with antiangiogenic agents. However, patients with similar clinicopathological aspects may present distinct outcome under AG inhibitors treatment. Single nucleotide polymorphisms (SNPs) in genes involved in blood vessels formation may constitute a plausible explanation for this finding. This study aimed to investigate the roles of VEGF c.-2595C > A (rs699947), c.-1154G > A (rs1570360), c.-634G > C (rs2010963), c.*237C > T (rs3025039), VEGFR2 c.-906T > C (rs2071559) and c.889G > A (rs2305948) SNPs, and GSTM1 and GSTT1 genes in outcome of MM patients treated with thalidomide-based regimen.

Methods

The study comprised 102 MM patients diagnosed between June 2005 and June 2013. The tumor was diagnosed and staged by standard criteria. Therapeutic regimens consisted in thalidomide combined with steroids and chemotherapy, followed or not by autologous steam cell transplantation. Response was evaluated at the end of therapy using the International Myeloma Working Group guidelines. Genotypes were analyzed in genomic DNA by polymerase chain reaction based methods. The chi-square test and logistic regression model were used to identify variables influencing response to therapy. Survival was estimated by Kaplan-Meier method, log-rank test and Cox hazards models.

Results

Patients with the wild-type allele of VEGF c.-2595C > A alone or plus the wild-type allele of VEGFR2 c.-906T > C SNPs, and the CGGC haplotype of all respective VEGF SNPs had 3.55, 9.91, and 3.86 more chances of achieving better response to therapy than others. At 60 months of follow-up, patients with VEGFR2 c.889GG, VEGF c.-634GG plus VEGFR2 c.889GG, and VEGFR2 c.889GG plus GSTM1 present genotypes had 2.62, 2.64, and 2.80 more chances of presenting disease relapse or progression, and 2.21, 4.88, and 4.23 more chances of evolving to death in multivariate analysis, respectively.

Conclusions

Our data present, for the first time, a preliminary evidence that VEGF c.-2595C > A, c.-1154G > A, c.-634G > C, c.*237C > T, VEGFR2 c.-906T > C and c.889G > A SNPs, and GSTM1 gene alter outcome of MM patients under thalidomide therapy.

Clinical trial identification

Not applicable

Legal entity responsible for the study

University of Campinas

Funding

N/A

Disclosure

All authors have declared no conflicts of interest.