-196 to -174del, rs4696480, rs3804099 polymorphisms of Toll-like receptor 2 gene impact the susceptibility of cancers: evidence from 37053 subjects

Abstract

Relationship between Toll-like receptor-2 (TLR2) and cancer risk has been illustrated in some studies, but their conclusions are inconsistent. Therefore, we designed this meta-analysis to explore a more accurate conclusion of whether TLR2 affects cancer risks. Articles were retrieved from various literature databases according to the criteria. We used STATA to calculate the odds ratio (OR) and 95% confidence interval (95% CI) to evaluate the relationship between certain polymorphism of TLR2 and cancer risk. Finally, 47 case-control studies met the criteria, comprising 15851 cases and 21182 controls. In the overall analysis, people are more likely to get cancer because of -196 to -174del in TLR2 in all five genetic models, B vs. A (OR = 1.468, 95% Cl = 1.129-1.91, P=0.005); BB vs. AA (OR = 1.716, 95% Cl = 1.178-2.5, P=0.005); BA vs. AA (OR = 1.408, 95% Cl = 1.092-1.816, P=0.008); BB+BA vs. AA (OR = 1.449, 95% Cl = 1.107-1.897, P=0.007); BB vs. BA+AA (OR = 1.517, 95% Cl = 1.092-2.107, P=0.013). Meanwhile, rs4696480 could significantly increase the risk of cancer in Caucasians, furthermore, rs3804099 significantly decreased cancer risk in overall analysis, but more subjects are necessary to confirm the results. All in all, this meta-analysis revealed that not only -196 to -174del increased the risk of among overall cancers, Caucasians are more likely to get cancer because of rs4696480, while rs3804099 polymorphism could reduce the risk of cancer in some genetic models. There is no direct evidence showing that rs5743708, rs3804100 and rs1898830 are related to cancer.Up to October 2019, PubMed, Embase, Google Scholar, Web of Science, Wanfang database and CNKI database were used by two investigators for article identification. We used the following strategy for the searching of relevant citations: (TLR2 OR (Toll-like receptors-2) OR CD282) AND (cancer OR tumor OR carcinoma OR neoplasms OR malignancy) AND (polymorphism OR mutation OR variant OR SNP OR genotype). Since the present study is a meta-analysis, no institutional review board approval and patient consent were required.

Fusobacterium nucleatum Extracellular Vesicles Modulate Gut Epithelial Cell Innate Immunity via FomA and TLR2

“…Even though the observed EV-based stimulation of TLR2 may indicate possible beneficial effects, human Tlr2 polymorphisms have complex roles in several diseases, including rheumatoid arthritis, type I diabetes or colorectal cancer (69). In the gut, specific Tlr2 polymorphisms have protective effects while others are associated with an increased risk of colorectal cancer depending on the populations (70)(71)(72)(73). Interestingly, Tlr2 but not Tlr4 expression is increased in cancerous tissues compared to non-cancerous adjacent tissues (47,74).…”

Role of toll-like receptors in complications of cardiac surgery for congenital heart defects in children

“…Кроме того, его минорный аллель C ассоциирован с устойчивостью к формированию рака желудка у пациентов с Helicobacter pylori [12]. Метаанализ, посвященный роли генов TLR в детерминировании рака различной локализации, показал, что именно полиморфный вариант rs3804099 гена TLR2 снижает риск онкологических заболеваний [13].…”

TheXRCC4rs1805377 polymorphism is not associated with the risk of cancer: An updated meta-analysis

“…To predict the potential association between rs1805377 and XRCC4 expression, we conducted expression quantitative trait loci (eQTL) analysis using the GTEx portal website (http://www.gtexportal.org/home/). 17,18…”

“…13 This polymorphic locus was reported to be involved in the occurrence of different cancers and the tumor diffusing capacity. [14][15][16][17][18] However, the findings of these studies are inconclusive because of small population sizes, genetic heterogeneity of samples, and other forms of possible confounding bias.…”