Methods and kits for determining a risk to develop cancer, for evaluating an effectiveness and dosage of cancer therapy and for correlating between an activity of a dna repair enzyme and a cancer

Abstract

Methods and kits for (i) determining a risk of a subject to develop cancer; (ii) evaluating an effectiveness and dosage of cancer therapy administered to a cancer patient; and (iii) determining a presence of correlation or non-correlation between an activity of at least one DNA repair enzyme and at least one cancer, are disclosed.

1 . A method of determining a risk of a subject to develop cancer, the method comprising determining a level of catalytic activity of a DNA repair enzyme in a biological sample of the subject, wherein said DNA repair enzyme is selected from the group consisting of 8-oxoguanine DNA glycosylase (OGG1), AP endonuclease1 (APE1), methylpurine DNA glycosylase (MPG), uracil DNA glycosylase1 (UNG1), uracil DNA glycosylase2 (UNG2), SMUG1, MBD4, mismatch-specific thymine/uracil glycosylase (TDG), enodonuclease III (NTH1), adenine-specific mismatch DNA glycosylase (MYH), 8-oxo-GTPase/8-oxodGTPase (MTH1), dUTPase (DUT), AP endonuclease2 (APE2), deoxyribose phosphate lyase (POLB) and wherein a level of said activity below a predetermined value is indicative of an increased risk of the subject to develop said cancer. 
     
     
         2 . The method of  claim 1 , wherein said cancer is selected from the group consisting of lung cancer, colorectal cancer and head and neck cancer. 
     
     
         3 . The method of  claim 1 , wherein the subject is known to be, or is about to be, exposed to environmental conditions associated with increased risk of developing said cancer. 
     
     
         4 . The method of  claim 3 , wherein said environmental conditions are selected from the group consisting of smoking and occupational exposure to smoke or ionizing radiation. 
     
     
         5 . The method of  claim 1 , wherein when said level of catalytic activity of said subject is below said predetermined level, indicative of increased risk of said subject to develop cancer, further counseling said subject to avoid exposure to ionizing radiation or smoke. 
     
     
         6 . The method of  claim 1 , wherein said DNA-repair enzyme is APE1 and said cancer is lung cancer or colorectal cancer. 
     
     
         7 . The method of  claim 6 , wherein when said level of catalytic activity of said subject is below said predetermined level, indicative of increased risk of said subject to develop cancer, further counseling said subject to avoid exposure to ionizing radiation or smoke. 
     
     
         8 . The method of  claim 1 , wherein said DNA-repair enzyme is MPG and said cancer is lung cancer or colorectal cancer. 
     
     
         9 . The method of  claim 8 , wherein when said level of catalytic activity of said subject is below said predetermined level, indicative of increased risk of said subject to develop cancer, further counseling said subject to avoid exposure to ionizing radiation or smoke. 
     
     
         10 . A method of determining a risk of a subject to develop colorectal cancer, the method comprising determining a level of catalytic activity of 8-oxoguanine DNA glycosylase in a sample of peripheral blood lymphocytes of the subject and, according to said level, determining the risk of the subject to develop colorectal cancer, wherein a level of said activity below a predetermined value is indicative of an increased risk of said subject to develop colorectal cancer. 
     
     
         11 . The method of  claim 10 , wherein said level of catalytic activity is determined using a double-stranded DNA substrate comprising the complementary oligonucleotides having a polynucleotide sequence as set forth in SEQ ID NOs: 1 and 2. 
     
     
         12 . The method of  claim 10 , wherein when said level of catalytic activity of said subject is below said predetermined level, indicative of increased risk of said subject to develop cancer, further counseling said subject to avoid exposure to ionizing radiation or smoke. 
     
     
         13 . A method of determining a risk of a subject to develop head and neck cancer, the method comprising determining a level of catalytic activity of 8-oxoguanine DNA glycosylase in a sample of peripheral blood lymphocytes of the subject and, according to said level, determining the risk of the subject to develop head and neck cancer, wherein a level of said activity below a predetermined value is indicative of an increased risk of said subject to develop head and neck cancer. 
     
     
         14 . The method of  claim 13 , wherein said level of catalytic activity is determined using a double-stranded DNA substrate comprising the complementary oligonucleotides having a polynucleotide sequence as set forth in SEQ ID NOs: 1 and 2. 
     
     
         15 . The method of  claim 13 , wherein when said level of catalytic activity of said subject is below said predetermined level, indicative of increased risk of said subject to develop cancer, further counseling said subject to avoid exposure to ionizing radiation or smoke. 
     
     
         16 . A method of predicting the efficacy of a mutagenic cancer treatment in a subject, the method comprising determining a level of catalytic activity of a DNA repair enzyme in a biological sample of the subject, and, according to said level, predicting the efficacy of the mutagenic anti-cancer treatment in the subject, wherein a level of said activity below a predetermined value is indicative of an increased efficacy of said mutagenic cancer treatment, wherein said DNA repair enzyme is selected from the group consisting of 8-oxoguanine DNA glycosylase (OGG1), AP endonuclease1 (APE1), methylpurine DNA glycosylase (MPG), uracil DNA glycosylase1 (UNG1), uracil DNA glycosylase2 (UNG2), SMUG1, MBD4, mismatch-specific thymine/uracil glycosylase (TDG), enodonuclease III (NTH1), adenine-specific mismatch DNA glycosylase (MYH), 8-oxo-GTPase/8-oxodGTPase (MTH1), dUTPase (DUT), AP endonuclease2 (APE2), deoxyribose phosphate lyase (POLB). 
     
     
         17 . The method of  claim 16 , wherein said mutagenic anti-cancer treatment is selected from the group of chemotherapy and radiotherapy. 
     
     
         18 . The method of  claim 16 , further comprising selecting dosage of said mutagenic anti-cancer treatment for treating the subject.