The Impact of IL-6 and IL-10 Gene Polymorphisms in Diffuse Large B-Cell Lymphoma Risk and Overall Survival in an Arab Population: A Case-Control Study.

Sohaib M Al-Khatib,Tariq Zuheir Kewan,Laith N Al-Eitan,Deeb Jamil Zahran,Abdel-Hameed Al-Mistarehi,Nour Abdo

doi:10.3390/cancers12020382

Abstract

B-cell lymphomas can be classified as Hodgkin and non-Hodgkin lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin Lymphoma (NHL). The incidence of NHL is variable and affected by age, gender, racial, and geographic factors. There is strong evidence that the immune-regulatory cytokines have a major role in hematologic malignancies. In this study, we analyzed the relationship between seven single nucleotide polymorphisms (SNPs) in two selected cytokines (IL-6 rs1800795G > C, rs1800796G > C, rs1800797G > A, IL-10 rs1800871G > A, rs1800872G > T, rs1800890A > T, rs1800896T > C) and the risk and overall survival of DLBCL patients in a Jordanian Arab population. One hundred and twenty-five DLBCL patients diagnosed at King Abdullah University Hospital (KAUH) from the period 2013–2018 and 238 matched healthy controls were included in the study. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissues. Genotyping of the genetic polymorphisms was conducted using a sequencing protocol. Our study showed no significant differences in the distribution of all studied polymorphisms of DLBCL between patients and controls. The IL-6 rs1800797 was the only SNP to show significant survival results, DLBCL subjects with the codominant model (GG/AG/AA) genotypes and recessive model (AA genotype in comparison with the combined GG/GA genotype) had worse overall survival (p = 0.028 and 0.016, respectively).

Highlights

Mature B-cell lymphomas are divided into Hodgkin and non-Hodgkin Lymphomas (HL and NHL) [1]
A total of 363 DNA samples were included in this study, namely, 238 healthy controls and 125
Additional analyses based on four genetic models were performed on all the single nucleotide polymorphisms (SNPs) and the results show no significant association between any of the genetic models and the risk of Diffuse large B-cell lymphoma (DLBCL)

Summary

Introduction

Mature B-cell lymphomas are divided into Hodgkin and non-Hodgkin Lymphomas (HL and NHL) [1]. NHL is considered the sixth most common type of cancer and the ninth leading cause of cancer deaths among both males and females [2,3]. Cancers 2020, 12, 382 infectious microorganisms, and lifestyle all play an important role in NHL pathogenesis [9,10,11,12]. Diffuse large B-cell lymphoma is the most common NHL [13]. Diffuse large B-cell lymphoma (DLBCL) is a diverse disease and genetically can be classified into two distinct types; the germinal center B-like type, characterized by the expression of germinal center B-cell genes, and the activated B-like type which shows gene expression of activated peripheral blood B cells. The germinal center B-like type shows better overall survival [14]

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