Polymorphisms for predicting disease and treatment outcome

Abstract

The invention provides compositions and methods for determining the increased risk for recurrence of certain cancers and the likelihood of successful treatment with one or both of chemotherapy and radiation therapy. The methods comprising determining the type of genomic polymorphism present in a predetermined region of the gene of interest isolated from the subject or patient. Also provided are nucleic acid probes and kits for determining a patient's cancer risk and treatment response.

1 . A method for selecting a therapeutic regimen for treating a cancer in a patient wherein a chemotherapeutic drug is administered to the patient, the method comprising screening a suitable cell or tissue sample isolated from said patient for a genomic polymorphism or genotype that is correlative to treatment outcome of the cancer. 
     
     
         2 . The method of  claim 1 , wherein the cancer is a cancer that can be treated by the administration of a chemotherapeutic drug selected from the group consisting of fluoropyrimidine or a platinum drug. 
     
     
         3 . The method of  claim 1 , wherein the cancer is selected from the group consisting of esophageal cancer, gastric cancer, colon cancer, rectal cancer, colorectal cancer and lung cancer. 
     
     
         4 . The method of  claim 2 , wherein the cancer treatment further comprises radiation therapy. 
     
     
         5 . The method of  claim 1 , wherein said genomic polymorphism occurs in the gene selected from the group consisting of thymidylate synthase gene, excision repair complementation group gene (ERCC1), VEGF, ERC2 gene, XRCC-1 gene, human glutathione s-transferase P1 gene, epidermal growth factor receptor gene, matrix metalloproteinase genes (-1, and -3), interleukin 8 (IL-8) gene, D-pyrimidine dehydrogenase (DPD) and CXC chemokine. 
     
     
         6 . The method of  claim 5 , wherein the genotype is high expression of a gene selected from the group consisting of thymidylate synthase, D-pyrimidine dehydrogenase (DPD) ERCC1 and VEGF and said tissue sample is normal tissue that corresponds to the tumor type. 
     
     
         7 . A method for reducing chemically induced neurotoxicity associated with cancer chemotherapy in a patient comprising administering to said subject an effective amount of a COX-2 inhibitor to a patient in need thereof. 
     
     
         8 . The method of  claim 7 , wherein the chemotherapy comprises administration of oxaliplatin. 
     
     
         9 . The method of  claim 7 , wherein the chemotherapy comprises administration of 5-FU. 
     
     
         10 . A method for determining if a human patient is more likely to experience tumor recurrence after surgical removal of said tumor, comprising determining the expression level of a gene selected from the group consisting of TS, DPD, ERCC1 and VEGF, in a cell or sample isolated from normal tissue adjacent to said tumor and correlating said expression level with normal levels, wherein overexpression of said gene is predictive to identify patients at risk for tumor recurrence. 
     
     
         11 . The method of  claim 11 , wherein the tumor is associated with rectal cancer.