Heme Oxygenase-1 Germ Line GTn Promoter Polymorphism is an Independent Prognosticator of Tumor Recurrence and Survival in Pancreatic Cancer

Background: Heme oxygenase-1 (HO-I) correlates with aggressive tumor behavior and chemotherapy resistance in pancreatic cancer (PC). We evaluated the prognostic value of the basal transcription controlling germ line GTn repeat polymorphism (GTn) in the promoter region of the HO-1 gene in PC. Patients and methods: We determined the GTn in 100 controls and 150 PC patients. DNA was extracted from blood leukocytes and GTn determined by PCR, electrophoresis, and sequencing. Clinicopathological parameters, disease-free, and overall survival (DFS, OS) were correlated with GTn. Results: Three genotypes were defined based on short (S) <25 and long (L) >= 25 GTn repeat alleles. In PC patients, a steadily increasing risk was evident between LL, SL, and SS genotype patients for larger tumor size, presence of lymph node metastasis, poor tumor differentiation and higher recurrence rate (P < 0.001 each). The SS genotype displayed the most aggressive tumor biology. The LL genotype had the best and the SS genotype the worst DFS and OS (P < 0.001 each). The GTn genotype was the strongest prognostic factor for recurrence and survival (P < 0.001 each). Conclusion: The GTn repeat polymorphism is a strong prognostic marker for recurrence and survival in PC patients. J. Surg. Oncol. 2011:104:305-311. (C) 2011 Wiley-Liss, Inc.