10.3389/fonc.2019.01056.s001
Szymon Zmorzyński
Szymon
Zmorzyński
Sylwia Popek-Marciniec
Sylwia
Popek-Marciniec
Aneta Szudy-Szczyrek
Aneta
Szudy-Szczyrek
Magdalena Wojcierowska-Litwin
Magdalena
Wojcierowska-Litwin
Iwona Korszeń-Pilecka
Iwona
Korszeń-Pilecka
Sylwia Chocholska
Sylwia
Chocholska
Wojciech Styk
Wojciech
Styk
Marek Hus
Marek
Hus
Agata A. Filip
Agata A.
Filip
Data_Sheet_1_The Association of GSTT1, GSTM1, and TNF-α Polymorphisms With the Risk and Outcome in Multiple Myeloma.docx
Frontiers
2019
GSTT1
GSTM1
TNF-alpha
rs1800629
rs361525
polymorphism
bortezomib
apoptosis
2019-10-11 14:53:17
Dataset
https://frontiersin.figshare.com/articles/dataset/Data_Sheet_1_The_Association_of_GSTT1_GSTM1_and_TNF-_Polymorphisms_With_the_Risk_and_Outcome_in_Multiple_Myeloma_docx/9971381
<p>Oxidative stress and systemic inflammation are closely linked with increased risk of cancer development. Tumor necrosis factor alpha (TNF-α) is one of the pro-inflammatory cytokines. Glutathione S-transferases (GSTs) are enzymes involved in oxidative stress handling. Polymorphisms of genes encoding mentioned molecules may potentially influence the risk and the outcome in neoplastic diseases. Multiple myeloma (MM) is a hematological malignancy characterized by clonal, atypical plasma cell proliferation. In the present study we investigated the association of deletion polymorphisms in GSTT1/GSTM1 genes and single nucleotide polymorphisms (SNPs) in the TNF-α gene at positions −308/−238 with the risk and outcome in MM and sensitivity to bortezomib under in vitro conditions. One hundred newly diagnosed MM patients and 100 healthy blood donors were genotyped by means of multiplex PCR (for GSTs) and PCR-RFLP (for TNF-α). In a subgroup of 50 MM patients, bone marrow cells were treated with bortezomib in vitro. Patients with −238GA+AA or GSTT1-null genotypes had 2.0 (p = 0.002) or 2.29 (p = 0.013) fold increased risk of MM. The interaction effects and risk of MM were observed in GSTT1/GSTM1-null (OR = 2.82, p = 0.018), −308/−238GA+AA (OR = 5.63, p < 0.001), as well as in all combinations of −308 with GSTs. The −308/−238GA+AA genotypes in comparison to GG were associated with earlier MM onset−61.14 vs. 66.86 years (p = 0.009) and 61.72 vs. 66.52 years (p = 0.035), respectively. Patients with GSTM1-present had shorter progression-free-survival (15.17 vs. 26.81 months, p = 0.003) and overall-survival (22.79 vs. 34.81 months, p = 0.039) compared with GSTM1-null. We did not observe relationship between response rate and studied polymorphisms. The in vitro study revealed significantly higher number of apoptotic cells at 12 nM of bortezomib in GSTT1-present, GSTM1-null/present, −308GG and −238GG/GA+AA genotypes. Our findings comprise large analysis of studied polymorphisms in MM.</p>