Genetic polymorphisms in the prostate-specific antigen gene promoter

Abstract

The present invention includes methods of identifying a subject at risk for increased cellular PSA production and/or prostate cancer by detecting the presence or absence of a genetic polymorphism in the prostate specific antigen gene.

1 . A method of screening a human male subject for increased risk of prostate cancer, comprising:
 detecting the presence or absence of a mutation at position −4643, −5307, −5412 or −5429 in the promoter of the prostate specific antigen (PSA) gene in a biological sample collected from said subject; and, if the mutation is present,   determining that the subject is at an increased risk of prostate cancer due to the presence of said mutation in the PSA gene.   
     
     
         2 . The method according to  claim 1 , wherein said mutation is at position −4643 in the promoter of the PSA gene, and wherein a G at said position −4643 indicates increased risk of prostate cancer. 
     
     
         3 . The method according to  claim 1 , wherein said mutation is at position −5307 in the promoter of the PSA gene, and wherein a G at said position −5307 indicates increased risk of prostate cancer. 
     
     
         4 . The method according to  claim 1 , wherein said mutation is at position −5412 in the promoter of the PSA gene, and wherein a C at said position −5412 indicates increased risk of prostate cancer. 
     
     
         5 . The method according to  claim 1 , wherein said mutation is at position −5429 in the promoter of the PSA gene, and wherein a G at said position −5429 indicates increased risk of prostate cancer. 
     
     
         6 . The method of  claim 1 , wherein the detecting step includes a probe hybridization step. 
     
     
         7 . The method of  claim 1 , wherein the detecting step includes a nucleic acid amplification step. 
     
     
         8 . The method of  claim 1 , wherein the detecting step includes a restriction enzyme digestion step. 
     
     
         9 . The method of  claim 1 , wherein said detecting step further comprises detecting whether said subject is homozygous for said mutation. 
     
     
         10 . A method of diagnosing prostate cancer or a genetic predisposition for developing prostate cancer in a human male subject, comprising:
 providing a biological sample from the subject, wherein said sample comprises a nucleic acid comprising a promoter of the prostate specific antigen (PSA) gene; and   detecting whether the subject has one or more mutations at position −4643, −5307, −5412 or −5429 in the promoter of the PSA gene,   wherein the presence of one or more mutations at position −4643, −5307, −5412 or −5429 in the promoter of the PSA gene is diagnostic for prostate cancer or a genetic predisposition for developing prostate cancer in the subject.   
     
     
         11 . The method according to  claim 10 , wherein said mutation is at position −4643 in the promoter of the PSA gene, and wherein a G at said position −4643 indicates increased risk of prostate cancer. 
     
     
         12 . The method according to  claim 10 , wherein said mutation is at position −5307 in the promoter of the PSA gene, and wherein a G at said position −5307 indicates increased risk of prostate cancer. 
     
     
         13 . The method according to  claim 10 , wherein said mutation is at position −5412 in the promoter of the PSA gene, and wherein a C at said position −5412 indicates increased risk of prostate cancer. 
     
     
         14 . The method according to  claim 10 , wherein said mutation is at position −5429 in the promoter of the PSA gene, and wherein a G at said position −5429 indicates increased risk of prostate cancer. 
     
     
         15 . The method of  claim 10 , wherein said detecting step further comprises detecting whether said subject is homozygous for said one or more mutations. 
     
     
         16 . The method of  claim 10 , wherein the nucleic acid is genomic DNA. 
     
     
         17 . The method of  claim 10 , wherein said detecting step comprises detecting two or more of said mutations. 
     
     
         18 . The method of  claim 10 , wherein the detecting step includes a probe hybridization step. 
     
     
         19 . The method of  claim 10 , wherein the detecting step includes a nucleic acid amplification step. 
     
     
         20 . The method of  claim 10 , wherein the detecting step includes a restriction enzyme digestion step.