Background: More than 40 % of patients with submucosal esophageal squamous cell carcinoma (ESCC) have lymph node metastasis. Furthermore, the potential presence of undetectable metastasis before treatment prompts surgeons to be aggressive with respect to lymph node dissection. Extending the indication for endoscopic resection, a minimally invasive treatment, to superficial ESCCs will require more accurate and individualized evaluation of lymph node metastasis. Methods: The study participants were 121 esophageal cancer patients who underwent curative surgery for thoracic submucosal ESCC at three Japanese hospitals. DNA was extracted from blood samples, and the C-reactive protein (CRP) 1846C>T genetic polymorphism (rs1205) was investigated using polymerase chain reaction-restriction fragment length polymorphism. We then evaluated the value of CRP 1846C>T polymorphism for diagnosis of lymph node metastasis. Results: Forty-nine (40 %) patients had lymph node metastasis. The CRP 1846 C/T genotype was C/C in 19 patients, C/T in 57 patients, and T/T in 45 patients. Fisher's exact analysis of the CRP 1846C>T polymorphism showed a significantly higher frequency of lymph node involvement with the T/T genotype. Univariate and multivariate logistic regression models revealed that patients carrying the 1846 T/T genotype had a significantly greater likelihood of developing lymph node metastasis (odds ratio >2.6). Combining the CRP 1846 C/T genotype with clinical diagnosis, mainly using CT, brought a negative predictive value of 80 % to diagnosing lymph node involvement. Conclusions: CRP genetic polymorphism may be a novel predictor of risk of lymph node metastasis in ESCC, which could enable better evaluation of the necessity for lymph node dissection.
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