Polymorphisms in checkpoint kinase 2 may contribute to lymph node metastasis from esophageal cancer.

ABSTRACT

Esophageal cancer, which is commonly accompanied by lymph node metastasis, is among the deadliest of cancers and carries a grim prognosis. We investigated the association between genetic variation in checkpoint kinase 2 (CHEK2), which has been linked to metastasis in other cancers, and the risk of developing lymph node metastasis from esophageal cancer. CHEK2-122 G/C genotypes were determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in 296 subjects with esophageal cancer (67 cases with and 229 cases without lymph node metastasis). The associations between CHEK2 genotypes and the risk of lymph node metastasis from esophageal cancer were estimated by computing odds ratios (OR) and their 95% confidence intervals (CI). The CHEK2 GG, GC, and CC genotype frequencies in patients with and without lymph node metastasis were 47.8%, 40.3%, and 11.9% and 31.0%, 50.7%, and 18.3% respectively, and were statistically significant (χ(2) =6.591, P=0.037). Logistic regression analyses revealed that the CHEK2-122 GC genotype significantly reduced the risk of lymph node metastasis (adjusted OR=0.54, 95% CI=0.29-0.93, P=0.028) compared to the GG genotype. Subsequently, we propose that the CHEK2-122 G/C polymorphism may play a protective role in preventing lymph node metastasis from esophageal cancer, and may also provide insight toward determining patient prognosis without the use of surgery.