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

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.