Methods for identifying an increased risk of anthracycline-related cardiotoxicity
Methods of identifying a subject having an increased risk of developing anthracycline-related cardiotoxicity are provided. Such methods may include isolating a DNA sample from a biological specimen from the subject; genotyping the DNA sample to determine a copy number of a variant allele that increases the risk of developing chemotherapy-induced cardiotoxicity; and identifying the subject as having an increased risk of developing anthracycline-related cardiotoxicity when the copy number is at least one. In some embodiments, the methods may include optimally administering a therapeutically effective dose of a chemotherapy agent or an alternative non-cardiotoxic chemotherapeutic agent to the subject.
1. A method for optimally administering an anthracycline to a cancer patient to prevent cardiotoxicity comprising:
genotyping a cancer patient using a whole genome or locus specific method to determine at least one copy of SNP rs2232228 (G>A) within an HAS3 gene, and optimally administering a therapeutically effective dose of the anthracycline to the patient, wherein the therapeutically effective dose comprises a cumulative dose of approximately 1-250 mg/m 2 .
2. The method of claim 1 , wherein the therapeutically effective dose comprises a cumulative dosage of approximately 1-150 mg/m 2 when the cancer patient carries two copies of the SNP rs2232228(G>A).
3. The method of claim 1 , wherein the anthracycline is doxorubicin, daunomycin, epirubicin, mitoxantrone, valrubicin, or idarubicin.
4. The method of claim 1 , wherein the anthracycline is administered in combination with one or more additional chemotherapeutics or cardioprotectants.
5. The method of claim 1 , wherein the cardiotoxicity prevented is cardiomyopathy or congestive heart failure (CHF).
6. A method of preventing anthracycline-induced cardiomyopathy in a cancer patient comprising:
genotyping a cancer patient using a whole genome or locus specific method to determine at least one copy of SNP rs2232228 (G>A) within an HAS3 gene, and optimally administering a therapeutically effective dose of an anthracycline to the patient, wherein the therapeutically effective dose is a low or moderate dose.
7. The method of claim 6 , wherein the patient has one copy of the SNP rs2232228(G>A) and the effective dose is a cumulative dosage of approximately 1-250 mg/m 2 .
8. The method of claim 6 , wherein the patient has two copies of the SNP rs2232228(G>A) and the effective dose is a cumulative dosage of approximately 1-150 mg/m 2 .
9. The method of claim 6 , wherein the anthracycline is doxorubicin, daunomycin, epirubicin, mitoxantrone, valrubicin, or idarubicin.
10. The method of claim 6 , wherein the anthracycline is administered in combination with one or more additional chemotherapeutics or cardioprotectants.