TNF-α -308 A allele is associated with an increased risk of distant metastasis in rectal cancer patients from Southwestern China

PLoS One. 2017 Jun 2;12(6):e0178218. doi: 10.1371/journal.pone.0178218. eCollection 2017.

Abstract

Tumor necrosis factor-α (TNF-α), an important factor in systematic inflammation, is reportedly involved in several cancer types. The TNF-α -308 G>A (rs1800629) polymorphism in the promoter region influences TNF-α production. The association between TNF-α -308 G>A polymorphism and colorectal cancer (CRC) is not fully understood, especially the connections between TNF-α -308 G>A polymorphism and clinical features of CRC. In this study, TNF-α -308 G>A polymorphism was genotyped in 1140 individuals with or without CRC from Southwestern China. In case-control studies, we found no association between TNF-α -308 G>A polymorphism and CRC risk. Analysis of the correlations between TNF-α -308 G>A polymorphism and clinical features of CRC revealed that TNF-α -308 A allele was associated with higher body mass index (BMI) larger tumor size, and distant tumor metastasis in all CRC patients. Notably, rectal cancer (a subtype of CRC) patients with TNF-α -308 A allele had a very high risk of distant tumor metastasis [odds ratio (OR) = 4.481; 95% confidence interval (CI): 2.072-9.693; P = 0.00025]. The association between TNF-α -308 A allele and distant tumor metastasis remained even significant after adjusting all clinical characteristics (OR = 7.099; 95% CI: 2.482-20.301; P = 0.000256) in rectal cancer patients. Our results suggested that TNF-α -308 A allele was significantly associated with distant tumor metastasis in rectal cancer patients.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • China
  • Colon / metabolism
  • Colon / pathology*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Polymorphism, Single Nucleotide*
  • Rectum / metabolism
  • Rectum / pathology*
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Tumor Necrosis Factor-alpha

Grants and funding

This study was supported by the Foundation of Leading Talent Program of Health and Family Planning Commission of Yunnan Province (No. L-201205), National Natural Science Foundation of China (No. 81460424), the Scholarship Award for Excellent Doctoral Student Grant of Yunnan Province, the Foundation of Medical Discipline Leaders Program of Health and Family Planning Commission of Yunnan Province (No. D-201668), the Foundation of the Institute of Gastroenterology, Research Institutions attached to the Health and Family Planning Commission of Yunnan Province (2014NS122), the Foundation of the Institute of Breast Surgery, Research Institutions attached to the Health and Family Planning Commission of Yunnan Province (2014NS022) and the Joint Special Research Funds of Kunming Medical University (2014FZ035). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.