Four genetic polymorphisms of lymphotoxin-alpha gene and cancer risk: a systematic review and meta-analysis

PLoS One. 2013 Dec 12;8(12):e82519. doi: 10.1371/journal.pone.0082519. eCollection 2013.

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, I(2) = 12.2%), rs2239704 (OR = 1.08, 99% CI = 1.01-1.16, P = 0.021, I(2) = 0.0%) and rs2229094 (OR = 1.28, 99% CI = 1.09-1.50, P = 0.003, I(2) = 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, I(2) = 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, I(2) = 0.0%), and rs2229094 was specific for the increased risk of adenocarcinoma (OR = 1.33, 99% CI = 1.11-1.59, P = 0.002, I(2) = 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Alleles
  • Case-Control Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Lymphotoxin-alpha / genetics*
  • Neoplasms / diagnosis
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Odds Ratio
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Publication Bias
  • Risk

Substances

  • Lymphotoxin-alpha

Grants and funding

The research was supported by grants from the National Natural Science Foundation of China (31100919), Natural Science Foundation of Zhejiang Province (LR13H020003), Medicine and health science and technology projects of Zhejiang province(2010KYB094, 2013KYB233), K.C. Wong Magna Fund in Ningbo University, Ningbo social development research projects (2011C50028, 2012C50027, 2012C50032), and Scientific Innovation Team Project of Ningbo (2011B82014), and Advanced key Scientific and Technological Programs of Ningbo (2011C51005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.