Effects of TNFalpha, NOS3, MDR1 Gene Polymorphisms on Clinical Parameters, Prognosis and Survival of Multiple Myeloma Cases

Abstract

It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFalpha), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasonecyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFalpha, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNFalpha (-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFalpha gene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNFalpha (-308) GG genotypes may have roles in myeloma pathogenesis.

Multidrug resistance 1 (MDR1/ABCB1) gene polymorphism (rs1045642 C > T) and susceptibility to multiple myeloma: a systematic review and meta-analysis

“…The sensitivity analysis showed reliability of our metaanalysis after removing non-HWE studies [30]. Except for the recessive model (Begg's test; z = −2.04, P = Figure 1.…”

“…A total of 98 studies were examined, and eventually according to the inclusion and exclusion criteria 4 eligible studies with 398 cases and 418 healthy subjects were included in this metaanalysis. The studies were conducted in different countries including Poland [27], North Ireland [28], China [29], and Turkey [30]. All eligible studies had an overall good methodological quality with an overall score ranging from 7 to 9.…”

“…Although the present meta-analysis did not find associations of the MDR 1 3435 C > T polymorphism and the risk of MM, the results should be interpreted with caution. More than 50 SNPs are defined for the MDR1 gene [30], but only the rs1045642 C > T polymorphism has been examined in MM patients. Accordingly, this meta-analysis was limited to one of the most investigated SNPs, and lack of association of rs1045642 C > T with MM in our analysis could not exclude the possible relationship between other SNPs of the MDR1 gene and MM risk.…”

The Genes of Life and Death: A Potential Role for Placental‐Specific Genes in Cancer

“…INSL4 encodes an insulin‐like hormone peptide in the placenta, and it has been labeled a candidate oncogene in somatic tissues due to its high levels of expression in thyroid and breast cancer (which has been shown to be upregulated by hypomethylation) . NOS3 is involved in the synthesis of nitric oxide in the cardiovascular system during pregnancy, yet it is also implicated in the pathogenesis of myeloma and laryngeal cancers . Lastly, the most well characterized placental RDG is ERVW‐1 ( ERVWE1 ), the gene for syncytin‐1, which plays an important role in the placenta by regulating the cell‐to‐cell fusion required for placental cell differentiation .…”

Association between tumor necrosis factor alpha gene polymorphisms and multiple myeloma risk: an updated meta-analysis

“…MM has a multifactorial etiology that is influenced by various environmental and genetic factors [5][6][7]. Recent evidences have confirmed the association between genetic polymorphisms and MM risk [8][9][10].…”