Carcinoma diagnosis and treatment, based on ODC1 genotype
The present invention provides methods and kits a) for predicting colorectal cancer patient survival, as well as the survival of patients harboring other invasive cancers where cellular proliferation and carcinogenesis is linked, in part, to high levels of ODC activity and increased cellular polyamine contents, and b) for selecting the corresponding treatment options for such patients based on the allelic nucleotide sequence or SNP at position +316 of the ODC1 promoter gene as well as cancer treatment methods, in each case, which include the determination of the ODC1 promoter +316 position genotype, as a means to guide treatment selection.
1. A method for preventing the development or recurrence of a carcinoma in a patient at risk therefor comprising:
a) obtaining results from a test that determines the patient's genotype at position +316 of at least one ODC1 promoter gene allele; and
b) administering to the patient combined effective amounts of a first agent that inhibits ornithine decarboxylase (ODC) within the patient and a second agent that modulates the polyamine pathway to reduce overall polyamine content within the patient when combined with the first agent if the results indicate that the patient's genotype at position +316 of at least one allele of the ODC1 promoter gene is G.
2. The method of claim 1 , wherein the results are obtained by receiving a report containing said genotype or taking a patient history that reveals the results.
3. The method of claim 1 , wherein the test determines the nucleotide base at position +316 of one allele of the ODC1 promoter gene of the patient.
4. The method of claim 1 , wherein the test determines the nucleotide bases at position +316 of both alleles of the ODC1 promoter gene of the patient.
5. The method of claim 4 , wherein the results indicate that the patient's genotype at position +316 of both alleles of the ODC1 promoter gene is GG.
6. The method of claim 4 , wherein the results indicate that the patient's genotype at position +316 of both alleles of the ODC1 promoter gene is GA.
7. The method of claim 1 , wherein the carcinoma is colorectal cancer, breast cancer, pancreatic cancer, brain cancer, lung cancer, stomach cancer, a blood cancer, skin cancer, testicular cancer, prostate cancer, ovarian cancer, liver cancer or esophageal cancer, cervical cancer, head and neck cancer, non-melanoma skin cancer, neuroblastoma and glioblastoma.
8. The method of claim 7 , wherein the carcinoma is colorectal cancer.
9. The method of claim 1 , wherein the method prevents ototoxicity or the risk thereof within the patient.
10. The method of claim 1 , wherein the patient has been diagnosed with familial adenomatous polyposis.
11. The method of claim 1 , wherein the patient has an intraepithelial neoplasia or a precancerous lesion and elevated cellular polyamine levels.
12. The method of claim 1 , wherein the patient is human.
13. The method of claim 1 , wherein the first agent is α-difluoromethylornithine (DFMO).
14. The method of claim 1 , wherein the second agent is a non-aspirin containing non-steroidal anti-inflammatory drug (NSAID).
15. The method of claim 14 , wherein the non-aspirin containing NSAID is a selective COX-2 inhibitor.
16. The method of claim 14 , wherein the non-aspirin containing NSAID is sulindac or celecoxib.
17. The method of claim 16 , wherein the non-aspirin containing NSAID is sulindac.
18. The method of claim 17 , wherein DFMO and sulindac are administered systemically.
19. The method of claim 17 wherein DFMO and sulindac are administered by distinct routes.
20. The method of claim 17 , wherein the DFMO or the non-aspirin containing NSAID is administered orally, intraarterially or intravenously.