Toll-like receptor 2 and 9 genetic polymorphisms and the susceptibility to B cell Non-Hodgkin Lymphoma in Egypt

Abstract

Non-Hodgkin lymphomas (NHL) entail considerable heterogeneity regarding their morphology, clinical course, etiological factors, or response to therapy. Increased incidence of NHL in immunocompromised individuals and after autoimmune diseases suggests that infections and immune dysregulation could play a role in the susceptibility to NHL. Accordingly, genetic variation in Toll-like receptor (TLR) genes might be considered as molecular risk factors for NHL. The aim of the current study was to investigate the possible association between genetic polymorphism of the TLRs genes and B cell NHL (B-NHL) risk in Egypt. The present study included 100 B-NHL patients and 100 healthy controls. Genotyping of TLR2-1350 T/C and TLR9-1237 T/C were done by polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP) technique. The frequency of TLR2-1350 T/C polymorphic genotypes in B-NHL patients was 18 % for the heteromutant genotype (TC) and 1 % for the homomutant (CC). There was no statistical difference in the distribution of TLR2-1350 T/C genotypes between B-NHL patients and controls. As for TLR9-1237 T/C, the frequency of the heteromutant genotype (TC) was 58 % and the homomutant genotype (CC) was 1 % in B-NHL patients. Calculated risk estimation revealed that TLR9-1237 (TC) heterotype conferred almost fourfold increased risk of B-NHL (odds ratio (OR) = 3.93, 95 % confidence interval (CI) = 2.16-7.14), and the risk was higher in patients with indolent subtypes (OR = 6.64, 95 %CI = 2.31-9.08). In conclusion, the study revealed that TLR9-1237 T/C polymorphism can be considered as molecular risk factor for B-NHL among Egyptians.

Association between <em>TLR-9</em> polymorphisms and colon cancer susceptibility in Saudi Arabian female patients

“…Several studies have shown that TLR-9 engagement on cluster of differentiation 4-positive (CD4 + ) T cells can enhance their survival and therefore potentiate anticancer responses by prolonging T-cell activity 14. Previous studies have indicated that TLR-9 polymorphisms may be associated with the risk of developing several types of cancers, including bladder cancer,15 prostate cancer,16–18 acute lymphoblastic leukemia,19 hepatocellular carcinoma,20 gastric cancer,21,22 cervical cancer,23 Hodgkin’s lymphoma,24 breast cancer,25 Burkitt’s lymphoma,26 non-Hodgkin’s lymphoma,27 endometrial cancer,28 esophageal cancer,23 and lymphoma 24,27,29. However, the results are inconsistent and inconclusive.…”

Association of TLR4 Rs4986791 Polymorphism and TLR9 Haplotypes with Acute Myeloid Leukemia Susceptibility: A Case-Control Study of Adult Patients

“…The variant heterozygous genotype of the TLR9 rs5743836 SNP conferred almost a fourfold increased risk of B-cell Non-Hodgkin lymphomas (B-NHL) in patients from Egypt (OR = 3.93, 95% CI = 2.16–7.14) [ 22 ]. This observation was supported neither by our study nor by the meta-analysis that included 25,685 subjects that suggested that the TLR9 rs352140 and rs5743836 SNPs were associated with a decreased risk of development of breast and digestive system cancers [ 34 ].…”

“…A small study that included 62 adult patients with AML from Poland showed that TLR9 rs5743836 and rs187084 gene polymorphisms were associated with predisposition to the disease [ 16 ]. TLR9 rs5743836, polymorphism may represent a molecular risk factor for B-cell Non-Hodgkin lymphomas (B-NHL) among Egyptian subjects [ 22 ]. No significant association between rs2066807 and rs187084 SNPs of the TLR9 genes and the risk of chronic lymphocytic leukemia (CLL) in the Egyptian population was reported previously [ 23 ].…”

Toll-like receptors-2 and -9 (TLR2 and TLR9) gene polymorphism in patients with type 2 diabetes and diabetic foot

“…[9] This generated a 135 bp fragment. The amplified material was digested by BstNI enzyme (Fermentas-Lithuania).…”