Association of toll-like receptor 2 ∆22 and risk for gastric cancer considering main effects and interactions with smoking: a matched case-control study from Mizoram, India

Tumour Biol. 2016 Aug;37(8):10821-6. doi: 10.1007/s13277-016-4982-5. Epub 2016 Feb 15.

Abstract

Toll-like receptors (TLRs) are evolutionary conserved cell surface receptors of the innate immune system. Smoking has significant immunological effects which are mediated via TLRs on various receptor-mediated innate response pathways. Polymorphisms of TLR genes are associated with susceptibility toward various malignancies. The present study was undertaken to examine the association between TLR2 ∆22 and gastric cancer. In this study, we also investigated the interaction between TLR2 ∆22 and smoking. A total of 133 histologically confirmed gastric cancer cases and 266 age-sex-matched controls were selected for this study. TLR2 ∆22 genotypes were determined by allele-specific polymerase chain reaction (PCR). Binary conditional logistic regression analysis was used to find the association of TLR2 ∆22 with risk of gastric cancer. Logistic regression using hierarchically well-formulated models was used for interaction analysis between smoking and TLR2 ∆22. Persons having TLR2 ∆22 heterozygous genotype had two times increased risk of gastric cancer in multivariate logistic regression model. The interaction analysis using hierarchical logistic regression models between smoking and TLR2 ∆22 by calculating separate X (2) for interaction model and only main effect model, the difference of X (2) 57.68-47.70 = 9.98 and degrees of freedom (df) 5-3 = 2, revealed significant (α = 0.05, df = 2) omnibus interaction. Our present study revealed TLR2 ∆22 to be significantly and independently associated with gastric cancer risk in Mizoram, and there is also evidence of significant interaction between smoking and TLR2 ∆22 with risk of gastric cancer.

Keywords: Gastric cancer; Interaction analysis; Logistic regression; Smoking; TLR2 ∆22.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • India
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Smoking / adverse effects*
  • Stomach Neoplasms / genetics*
  • Toll-Like Receptor 2 / genetics*

Substances

  • TLR2 protein, human
  • Toll-Like Receptor 2