Abstract
Purpose: To provide a comprehensive account of the association of five Lymphotoxin-α (LTA) gene polymorphisms (rs1041981, rs2229094, rs2239704, rs746868, rs909253) with susceptibility to cancer.Methods: A literature search for eligible candidate gene studies published before 28 February 2020 was conducted in the PubMed, Medline, Google Scholar and Web of Science. The following combinations of main keywords were used: (LTA OR Lymphotoxin alpha OR TNF-β OR tumor necrosis factor-beta) AND (polymorphism OR mutation OR variation OR SNP OR genotype) AND (cancer OR tumor OR neoplasm OR malignancy OR carcinoma OR adenocarcinoma). Potential sources of heterogeneity were sought out via subgroup and sensitivity analysis, and publication bias were estimated.Results: Overall, a total of 24 articles with 24577 cases and 33351 controls for five polymorphisms of LTA gene were enrolled. We identified that rs2239704 was associated with a reduced risk of cancer. While for other polymorphisms, the results showed no significant association with cancer risk. In the stratified analysis of rs1041981, we found that Asians might have less susceptibility to cancer. At the same time, we found that rs2239704 was negatively correlated with non-Hodgkin lymphoma (NHL). While, for rs909253, an increased risk of cancer for Caucasians and HCC susceptibility were uncovered in the stratified analysis of by ethnicity and cancer type.Conclusion: LTA rs2239704 polymorphism is inversely associated with the risk of cancer. LTA rs1041981 polymorphism is negatively associated with cancer risk in Asia. While, LTA rs909253 polymorphism is a risk factor for HCC in Caucasian population.
Highlights
Received: 04 July 2019Revised: 24 April 2020Accepted: 07 May 2020Accepted Manuscript online: 18 May 2020Version of Record published: 28 May 2020Increasing studies have demonstrated that a number of proinflammatory cytokines could be associated with the development of cancer [1,2]
While for other polymorphisms, the results showed no significant association with cancer risk
We found that rs2239704 was negatively correlated with non-Hodgkin lymphoma (NHL)
Summary
Received: 04 July 2019Revised: 24 April 2020Accepted: 07 May 2020Accepted Manuscript online: 18 May 2020Version of Record published: 28 May 2020Increasing studies have demonstrated that a number of proinflammatory cytokines could be associated with the development of cancer [1,2]. The presence of single nucleic polymorphism (SNP) may affect cytokine expression level, which might be an important mediator of cancer [6,7]. SNP rs1041981 is a mutation of LTA gene at the 804 (C/A) position of exon 3 in codon 26, causing the amino acid threonine to be asparagine, which may be related to the transcriptional regulation of LTA, activate the lymphocytes and induce apoptosis [8]. SNP rs909253 is a mutation of LTA gene at 252 (A/G) position in intron 1, which may lead to increase in the transcriptional activities of LTA [1]. SNP rs2239704, rs746868 and rs2229094 are associated with the LTA expression, which may affect subsequent inflammatory responses and immunomodulatory diseases, including cancers [9,10]
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