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Functional Promoter -308G>A Variant in Tumor Necrosis Factor α Gene Is Associated with Risk and Progression of Gastric Cancer in a Chinese Population

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  • Yan Hong
  • Zhijun Ge
  • Changrui Jing
  • Jun Shi
  • Xiao Dong
  • Fengying Zhou
  • Meilin Wang
  • Zhengdong Zhang
  • Weida Gong

Abstract

Background: Tumor necrosis factor-α (TNF-α) plays a crucial role in the development and progression of gastric cancer. A functional polymorphism, -308 G>A (rs1800629), which is located in the promoter of TNFA gene, has been suggested to alter the production of TNF-α and influence cancer risk. In the present study, we sought to investigate whether this polymorphism has effects on the risk and progression of gastric cancer in a Chinese population. Methods: We genotyped the TNFA -308 G>A polymorphism using the TaqMan method in a two-stage case-control study comprising a total of 1686 gastric cancer patients and 1895 cancer-free subjects. The logistic regression was used to assess the genetic associations with occurrence and progression of gastric cancer. Results: We found a significant association between the variant genotypes and increased risk of gastric cancer [P = 0.034, odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.01–1.67, GA/AA vs. GG]. Similar results were observed in the follow-up replication study. When combined the data from the two studies, we found a more significant association (P = 0.001, OR = 1.34, 95%CI = 1.13–1.59), especially for older subjects (>65 years). Furthermore, the patients carrying the variant genotypes had a significantly greater prevalence of T4 stage of disease (P = 0.001, OR = 2.19, 95%CI = 1.39–3.47) and distant metastasis (P = 0.013, OR = 1.61, 95%CI = 1.10–2.35). Conclusions: Our results suggest that the functional promoter -308 G>A polymorphism in TNFA influence the susceptibility and progression of gastric cancer in the Chinese population.

Suggested Citation

  • Yan Hong & Zhijun Ge & Changrui Jing & Jun Shi & Xiao Dong & Fengying Zhou & Meilin Wang & Zhengdong Zhang & Weida Gong, 2013. "Functional Promoter -308G>A Variant in Tumor Necrosis Factor α Gene Is Associated with Risk and Progression of Gastric Cancer in a Chinese Population," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-6, January.
    • Handle: RePEc:plo:pone00:0050856
    DOI: 10.1371/journal.pone.0050856
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    Cited by:

    1. Suzanne Vogelezang & Jonathan P Bradfield & Tarunveer S Ahluwalia & John A Curtin & Timo A Lakka & Niels Grarup & Markus Scholz & Peter J van der Most & Claire Monnereau & Evie Stergiakouli & Anni Hei, 2020. "Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits," PLOS Genetics, Public Library of Science, vol. 16(10), pages 1-26, October.
    2. Li Min & Duo Chen & Like Qu & Chengchao Shou, 2014. "Tumor Necrosis Factor-A Polymorphisms and Colorectal Cancer Risk: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-7, January.

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