CRP genetic polymorphism is associated with lymph node metastasis in thoracic esophageal squamous cell cancer

Ann Surg Oncol. 2009 Sep;16(9):2479-85. doi: 10.1245/s10434-009-0525-2. Epub 2009 Jun 3.

Abstract

Background: Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms and lymph node metastasis.

Methods: The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer. DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and -beta, interferon (IFN)-gamma, transforming growth factor (TGF)- beta, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between inflammation-related genes and lymph node metastasis.

Results: For CRP 1846C>T polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis (P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846C>T polymorphism for predicting lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative predictive values of 69% and 75%, respectively.

Conclusions: These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be useful for deciding on treatment strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • C-Reactive Protein / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / secondary
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Neoplasms / surgery
  • Female
  • Humans
  • Interleukin-1 / genetics
  • Interleukin-10 / genetics
  • Interleukin-2 / genetics
  • Interleukin-4 / genetics
  • Interleukin-6 / genetics
  • Lymph Nodes / pathology*
  • Lymph Nodes / surgery
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Receptors, Interleukin-10 / genetics
  • Receptors, Interleukin-6 / genetics
  • Survival Rate
  • Thoracic Neoplasms / genetics*
  • Thoracic Neoplasms / pathology
  • Thoracic Neoplasms / surgery
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Biomarkers, Tumor
  • Interleukin-1
  • Interleukin-2
  • Interleukin-6
  • Receptors, Interleukin-10
  • Receptors, Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • C-Reactive Protein