Artikel
The MAP3K1 Polymorphism predicts the postoperative natural course of completely resected only surgically treated esophageal cancer
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Veröffentlicht: | 20. Mai 2011 |
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Introduction: There is a paucity of prognostic markers in esophageal cancer (EC). Genetic variations in cancer patients may serve as important prognostic indicators of clinical outcome since germ line DNA remains unbiased by the genomic instability occurring in tumor tissue. A single nucleotide polymorphism mapping to the MAP3K1 gene at the rs889312 loci displays three genotypes (AA, AC and CC). The aim of this study was to evaluate the potential prognostic value of the MAP3K1 polymorphism in EC.
Materials and methods: Genomic DNA was extracted from peripheral blood leucocytes of 180 patients who underwent complete surgical resection for EC and did not receive any neoadjuvant or adjuvant therapy. The MAP3K1 genotype was correlated with clinico-pathological parameters, tumor cell dissemination in bone marrow and clinical outcome.
Results: Patients with the AA and AC genotype had more advanced disease predominantly due to bigger tumor size (p<0.01), presence of lymph node metastasis (p<0.0001)and higher rate of positive bone marrow for tumor cells (p=0.02) compared to CC carriers. Accordingly, the recurrence rate was higher in AA and AC patients (p<0.0001). Kaplan-Meier plots for disease-free (p<0.002) and overall survival (p<0.0001) displayed better outcome in CC compared to AA and AC patients. In tumor type and node-status stratified subanalyses MAP3K1 polymorphism was identified as a strong indipendent prognostic factor for recurrence (hazard ratio 8.7; p=0.03) and survival (hazard ratio 3.1; p=0.01) in EC patients.
Conclusion: MAP3K1 polymorphism allows allocation of esophageal cancer patients into different risk profiles and may help to identify patients eligible for neoadjuvant and or adjuvant therapy.