The genetic polymorphisms of immune‐related genes contribute to the susceptibility and survival of lymphoma

Abstract

BackgroundThough immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear.MethodsWe investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune‐related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA.ResultsBy comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK–STAT, NF‐κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter‐OS genotypes.ConclusionsWe used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune‐related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.

Association Analysis of Polymorphisms in Inflammation-Related Genes with Non-Hodgkin Lymphoma Susceptibility

“…A20 rs77191406 is a prognostic marker for rapid malignancy progression and poor survival of rheumatoid arthritis and systemic lupus erythematosus patients [16]. The IFNγ rs2069718 is associated with NHL patients' survival [9] and the risk of developing severe COVID-19 disease, which is caused by abnormally high levels of cytokines such as IFN-γ, IL-6, and TNF-α [20]. In addition, carriers of the JAK2 rs10974947 are linked to polycythemia vera susceptibility [13].…”

“…The immunogenetic investigations revealed that inflammation-related genes, including tumor necrosis factor α-induced protein 3 (TNFAIP3, A20), tumor suppressor cylindromatosis (CYLD), interferon (IFN)γ, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA), Janus kinase (JAK)2, tyrosine kinase (TYK)2 and tumor protein (TP)53 are associated with the survival, proliferation, and progression of tumor cells [6][7][8][9][10][11][12][13][14][15][16]. In our recent study, inactivations of A20 and CYLD lead to the pathogenesis of lymphomas [17][18][19].…”

“…JAK2 rs10974947 is associated with polycythemia vera [13]. The IFNγ rs2069718 is linked to the survival of NHL patients [9]. The TP53 rs1042522 is associated with the risk of NHL in China [10], but does not influence the survival of NHL patients in European Caucasians [6].…”

Circulating IL-6 and not its circulating signaling components sIL-6R and sgp130 demonstrate clinical significance in NSCLC patients treated with immune checkpoint inhibitors

“…3.4 Clinical significance of IL-6 (−634G>C) and IL-6R (48892A>C) genetic polymorphisms in non-small cell lung cancer patients treated with ICIs IL-6 or IL-6R genetic polymorphisms have been reported to be associated with risk or prognosis in patients with some cancers (DeMichele et al, 2009;Motoyama et al, 2012;Stephens et al, 2012;Kibe et al, 2014;Ruzzo et al, 2014;Zhang et al, 2017;Gu et al, 2023). Therefore, we investigated the clinical significance of genetic polymorphisms of IL-6 (−634G>C) and IL-6R (48892A>C) in NSCLC patients treated with ICIs.…”

“…It has been reported that IL-6 (−634G>C) and IL-6R (48892A>C) genetic polymorphisms are associated with the risk or prognosis in patients with some cancers ( DeMichele et al, 2009 ; Motoyama et al, 2012 ; Stephens et al, 2012 ; Kibe et al, 2014 ; Ruzzo et al, 2014 ; Zhang et al, 2017 ; Gu et al, 2023 ). For example, we previously demonstrated that the IL-6 (−634G>C) genetic polymorphism showed a significant association with prognosis after surgery in advanced thoracic esophageal squamous cell carcinoma ( Motoyama et al, 2012 ).…”