Prognostic role of TNF alpha, LT alpha, MDR1 and codon 72 Tp53 gene polymorphisms on multiple myeloma Egyptian patients

Heba M Hegazi; M S Elghonemy; M A El-Baiomy; Eman A Soliman; Elsayed K Abdel-Hady

doi:10.1016/j.leukres.2022.106854

Prognostic role of TNF alpha, LT alpha, MDR1 and codon 72 Tp53 gene polymorphisms on multiple myeloma Egyptian patients

Leuk Res. 2022 Jun:117:106854. doi: 10.1016/j.leukres.2022.106854. Epub 2022 Apr 29.

Authors

Heba M Hegazi¹, M S Elghonemy², M A El-Baiomy³, Eman A Soliman⁴, Elsayed K Abdel-Hady⁵

Affiliations

¹ Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt. Electronic address: Hebahegazi701@gmail.com.
² Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
³ Medical Oncology Unit, Oncology Center, Mansoura University Faculty of Medicine, Mansoura, Egypt.
⁴ Molecular Biology Department Oncology Center Mansoura University, Mansoura, Egypt.
⁵ Histology and Cytology Department, Faculty of Science, Mansoura University, Mansoura, Egypt.

PMID: 35594781
DOI: 10.1016/j.leukres.2022.106854

Abstract

Multiple Myeloma (MM) is a type of hematologic malignancies that characterized by uncontrolled plasma cell proliferation. So, the diagnosis depends on the increased numbers of abnormal, immature, or atypical plasma cells in the bone marrow, and many patients present with laboratory abnormalities, such as anemia, hypercalcemia, renal disease, and high protein levels in blood and urine. We aim to analyze the association of some genetic polymorphisms and its effect on the overall survival (OS) among MM patients.

Subjects and methods: We analyzed TNFα 308 G/A, TNFα 238 G/A, LTA252A/G, MDR 3435 C/T, MDR 1236 C/T, TP53 Arg72Pro in 110 multiple myeloma case and 112 healthy controls. The genotyping was performed using PCR-RFFLP.

Results: In TNF308 AA genotype and A allele were significantly lower with protective effect against MM development (OR=0.318, 0.742) respectively. LTA 252, GG genotypes had lower frequency in MM cases compared to control group with protective effect against MM development (OR=0.361). In TNF238, MDR1 3435 C/T, TP53 codon 72 polymorphism we didn't find any statistically significant relation between MM and control groups. In Uni and multivariant analysis show ISS, IgG, TP53 Arg72ProGC+CC as risk predictors of shorter OS.But TNFα-308 GA+AA and LTA 252 AG+GG were considered as predictors of longer OS in MM cases.

Conclusion: Our result confirms the association of TNF-308, LTA and TP53 codon72 with prognostic outcome in MM. As a result, we suggest involving these genes as a biomarker test to predicts the risk and prognostic outcome of MM. Also, we recommend further investigations of these polymorphisms in MM especially LTA and TP53codon 72 polymorphism which have very low reported studies.

Microabstract: Many genes can affect the prognosis of MM. We analyzed some of them in 110 MM and 112 controls using PCR-RFLP. TNFα-308 AA and LTA-252 GG had lower frequency while MDR1-1236 TT had higher frequency in MM. TNFα-308 AA and LTA-252 GG were significantly associated with higher OS but TP53 codon72 polymorphism CC with lower OS. These findings confirm the association of these genes with prognostic outcome in MM.

Keywords: LT alpha; MDR1; Multiple Myeloma; TNF alpha; TP53.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
Case-Control Studies
Codon
Egypt
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Lymphotoxin-alpha / genetics*
Multiple Myeloma* / genetics
Polymorphism, Single Nucleotide
Prognosis
Tumor Necrosis Factor-alpha* / genetics
Tumor Suppressor Protein p53 / genetics

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Codon
LTA protein, human
Lymphotoxin-alpha
TP53 protein, human
Tumor Necrosis Factor-alpha
Tumor Suppressor Protein p53