Genetic variants on chr 11q and 6q as markers for prostate and colorectal cancer predisposition

Abstract

It has been discovered that certain polymorphic markers on chromosome 6 and chromosome 11 are indicative of a susceptibility to prostate cancer and colon cancer. The invention describes diagnostic applications for determining a susceptibility to cancer using such markers, as well as kits for use in such applications.

1 . A method for determining a susceptibility to prostate cancer in a human individual, comprising determining the presence or absence of at least one allele of at least one polymorphic marker in a nucleic acid sample obtained from the individual, or in a genotype dataset from the individual, wherein the at least one polymorphic marker is selected from rs10896450 and rs10943605, and markers in linkage disequilibrium therewith, and wherein determination of the presence of the at least one allele is indicative of a susceptibility to prostate cancer. 
     
     
         2 . The method of  claim 1 , wherein the at least one polymorphic marker in linkage disequilibrium with rs10896450 is selected from the markers set forth in Table 5. 
     
     
         3 . The method of  claim 1 , wherein the at least one polymorphic marker in linkage disequilibrium with rs10896450 is selected from the markers set forth in Table 4. 
     
     
         4 . The method of  claim 3 , wherein the at least one polymorphic marker in linkage disequilibrium with rs10896405 is selected from rs11228565 and rs7947353. 
     
     
         5 . A method for determining a susceptibility to colorectal cancer in a human individual, comprising determining the presence or absence of at least one allele of at least one polymorphic marker in a nucleic acid sample obtained from the individual, or in a genotype dataset from the individual, wherein the at least one polymorphic marker is selected from rs10943605 and markers in linkage disequilibrium therewith, and wherein determination of the presence of the at least one allele is indicative of a susceptibility to colorectal cancer. 
     
     
         6 . The method of  claim 1 , wherein the at least one polymorphic marker in linkage disequilibrium with rs10943605 is selected from the markers set forth in Table 3. 
     
     
         7 . (canceled) 
     
     
         8 . The method of  claim 1 , wherein the susceptibility is increased susceptibility. 
     
     
         9 . The method of  claim 8 , wherein the presence of the at least one allele or haplotype is indicative of increased susceptibility with a relative risk of at least 1.10. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 8 , wherein the at least one marker or haplotype comprises at least one marker selected from the group consisting of rs10896450 allele G, rs11228565 allele A, rs7947353 allele A and rs10943605 allele G. 
     
     
         12 - 17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein linkage disequilibrium is characterized by values r 2  of greater than 0.2 and/or |D′| of greater than 0.8. 
     
     
         19 - 40 . (canceled) 
     
     
         41 . The method of  claim 1 , further comprising analyzing non-genetic information to make risk assessment, diagnosis, or prognosis of the individual. 
     
     
         42 . The method of  claim 41 , wherein the non-genetic information is selected from age, gender, ethnicity, socioeconomic status, previous disease diagnosis, medical history of subject, family history of cancer, biochemical measurements, and clinical measurements. 
     
     
         43 . The method of  claim 1 , further comprising assessing the presence or absence of at least one additional genetic risk factor for prostate cancer or colorectal cancer in the individual. 
     
     
         44 . The method of  claim 43 , wherein the additional genetic risk factor for prostate cancer is selected from the group consisting of rs2710646 allele A, rs16901979 allele A, rs1447295 allele A, rs6983267 allele G, rs10896450 allele G, rs1859962 allele G, rs4430796 allele A and rs5945572 allele A. 
     
     
         45 . The method of  claim 43 , further comprising calculating overall risk. 
     
     
         46 - 67 . (canceled) 
     
     
         68 . An apparatus for determining a genetic indicator for a cancer selected from prostate cancer and colorectal cancer in a human individual, comprising:
 a computer readable memory; and   a routine stored on the computer readable memory;   wherein the routine is adapted to be executed on a processor to analyze marker and/or haplotype information for at least one human individual with respect to at least one polymorphic marker selected from the markers set forth in Table 3 and Table 4, and markers in linkage disequilibrium therewith, and generate an output based on the marker or haplotype information, wherein the output comprises a risk measure of the at least one marker or haplotype as a genetic indicator of the cancer for the human individual.   
     
     
         69 . The apparatus of  claim 68 , wherein the routine further comprises an indicator of the frequency of at least one allele of at least one polymorphic marker or at least one haplotype in a plurality of individuals diagnosed with the cancer, and an indicator of the frequency of at the least one allele of at least one polymorphic marker or at least one haplotype in a plurality of reference individuals, and wherein a risk measure is based on a comparison of the at least one marker and/or haplotype status for the human individual to the indicator of the frequency of the at least one marker and/or haplotype information for the plurality of individuals diagnosed with the cancer. 
     
     
         70 . The apparatus of  claim 68 , wherein the at least one polymorphic marker is selected from marker rs10896450 and markers in linkage disequilibrium therewith, as defined by numerical values of r 2  of at least 0.2. 
     
     
         71 . The apparatus of  claim 68 , wherein the risk measure is characterized by an Odds Ratio (OR) or a Relative Risk (RR). 
     
     
         72 . The method of  claim 5 , wherein the at least one polymorphic marker in linkage disequilibrium with rs 10943605 is selected from the markers set forth in Table 3.