Four Genetic Polymorphisms of Lymphotoxin-Alpha Gene and Cancer Risk: A Systematic Review and Meta-Analysis

Abstract

Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine that plays an important role in the inflammatory and immunologic response. Numerous studies have shown LTA polymorphisms as risk factors for cancers, but the results remain inconclusive. The goal of the present meta-analyses is to establish the associations between cancers and four LTA variants (rs1041981, rs2239704, rs2229094 and rs746868). A total of 30 case-control studies involving 58,649 participants were included in the current meta-analyses. Our results showed significant associations with increased cancer risk for rs1041981 (odd ratio (OR) = 1.15, 99% confidential interval (CI) = 1.07-1.25, P < 0.0001, I2 = 12.2%), rs2239704 (OR = 1.08, 99% CI = 1.01-1.16, P = 0.021, I2 = 0.0%) and rs2229094 (OR = 1.28, 99% CI = 1.09-1.50, P = 0.003, I2 = 0.0%). No evidence was found for the association between rs746868 and cancer risk (OR = 1.01, 99% CI = 0.93-1.10, P = 0.771, I2 = 0.0%). Subgroup meta-analysis suggested that rs2239704 was likely to increase the risk of hematological malignancy (OR = 1.10, 99% CI = 1.01–1.20, P = 0.023, I2 = 0.0%), and rs2229094 was specific for the increased risk of adenocarcinoma (OR = 1.33, 99% CI = 1.11-1.59, P = 0.002, I2 = 0.0%). In conclusion, our meta-analyses suggested that the LTA rs1041981, rs2239704 and rs2229094 polymorphisms contributed to the increased risk of cancers. Future functional studies were needed to clarify the mechanistic roles of the three variants in the cancer risk.

Clinical aspects and polymorphisms in the LTA, TNFA, LTB genes and association with dental implant loss

“…The cancer can develop from a long proinflammatory response, in addition to genetic factors and cumulative effects of hormonal and environmental exposure . LTA gene polymorphisms rs2229094 and rs2009658 were associated with several types of cancer . Allele C of LTA rs2009658 was significantly increased in middle‐aged women with breast cancer.…”

“…[16][17][18][19] In this context, the Tumor Necrosis Factor (TNF) family has an important proinflammatory and immunological function, which influences the modulation of the extracellular matrix, affecting bone formation and remodeling. [20][21][22][23] Lymphotoxin alpha (LTA) is part of the TNF family and is a cytokine produced by lymphocytes, and a mediator of the acute inflammatory response 24 Tumor Necrosis Factor alpha (TNFA) is a cytokine secreted mainly by macrophages 25 , and it is a sentinel that acts as host defense at aggressions sites, and induces the production of other mediators of the inflammatory cascade and tissue destruction. Lymphotoxin beta (LTB) is also part of the TNF family.…”

Functional characterization of rs2229094 (T&gt;C) polymorphism in the tumor necrosis factor locus and lymphotoxin alpha expression in human retina: the Retina 4 project

“…Besides, LTA gene is located within TNF locus, and it is closely linked to TNFα and lymphotoxin beta genes. Therefore, modifications derived from functional SNPs in any of these could lead to collateral alterations in the neighboring genes 48. In addition, only three normal retinas and two peripheral blood samples could be analyzed to assess the mRNA and protein expression of LTA, due to the scarcity of this material and strict inclusion criteria in the obtention of samples.…”

Association between Phosphatase Related Gene Variants and Coronary Artery Disease: Case-Control Study and Meta-Analysis

“…Statistical heterogeneity between studies was estimated using the Q-test [64] and inconsistency index (I 2 statistic) [64]. An I 2 value >50% indicated a significant heterogeneity among the studies included in the meta-analysis [64].…”