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 subject for a genetic predisposition for increased cellular PSA production, comprising: 
 detecting the presence or absence of a mutation wherein said mutation is 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    determining that the subject is at an increased risk of a genetic predisposition for increased cellular PSA production due to the presence of said mutation in the PSA.    
     
     
         2 . The method according to  claim 1 , wherein the promoter of the PSA comprises a sequence from an androgen responsive element III.  
     
     
         3 . The method according to  claim 1 , wherein said mutation at position 4643 is G4643A.  
     
     
         4 . The method of  claim 1 , wherein said mutation at position 5307 is G5307A.  
     
     
         5 . The method according to  claim 1 , wherein said mutation at position 5412 is C5412T.  
     
     
         6 . The method according to  claim 1 , wherein said mutation at position 5429 is T5429G.  
     
     
         7 . The method of  claim 1 , wherein the detecting step includes a probe hybridization step.  
     
     
         8 . The method of  claim 1 , wherein the detecting step includes a nucleic acid amplification step.  
     
     
         9 . The method of  claim 1 , wherein the detecting step includes a polymerase chain reaction step.  
     
     
         10 . The method of  claim 1 , wherein said detecting step further comprises detecting whether said subject is homozygous for said mutation.  
     
     
         11 . The method of  claim 1 , wherein said genetic predisposition for increased cellular PSA production comprises determining if the subject is at an increased risk of prostate cancer.  
     
     
         12 . A method of diagnosing prostate cancer or a genetic predisposition for developing prostate cancer in a human subject, comprising: 
 providing a biological sample from the subject wherein said sample encodes a promoter of the prostate specific antigen;    detecting one or more mutations in the biological sample, and    determining that the subject has at least one detected mutation in each genomic copy of the biological sample encoding the promoter of the prostate specific antigen, wherein the presence of at least one detected mutation in each copy of the sequence encoding the promoter of the prostate specific antigen is diagnostic for prostate cancer or a genetic predisposition for developing prostate cancer in the subject, and wherein said mutation occurs at position 4643, 5307, 5412 or 5429 in the promoter of the prostate specific antigen gene.    
     
     
         13 . The method of  claim 12 , wherein the promoter of the PSA comprises a sequence from an androgen responsive element III.  
     
     
         14 . The method of  claim 12 , wherein said biological sample is a nucleic acid sequence.  
     
     
         15 . The method of  claim 12 , wherein said mutation at position 4643 is G4643A.  
     
     
         16 . The method of  claim 12 , wherein said mutation at position 5307 is G5307A.  
     
     
         17 . The method of  claim 12 , wherein said mutation at position 5412 is C5412T.  
     
     
         18 . The method of  claim 12 , wherein said mutation at position 5429 is T5429G.  
     
     
         19 . The method of  claim 12 , wherein the presence of at least one detected mutation is detected in one genomic copy of the sequence encoding the PSA, and the subject is a heterozygous carrier of the mutation associated with prostate cancer.  
     
     
         20 . The method of  claim 12 , wherein the presence of at least one detected mutation is detected in one genomic copy of the sequence encoding the PSA and the subject is a homozygous carrier of the mutation associated with prostate cancer.  
     
     
         21 . The method of  claim 12 , wherein the presence of at least one detected mutation is detected in each genomic copy of the sequence encoding the PSA.  
     
     
         22 . A method of screening for increased levels of PSA comprising: 
 providing a biological sample from a subject wherein said sample encodes a promoter of the prostate specific antigen;    detecting one or more mutations in the biological sample, and    determining that the subject has at least one detected mutation in a genomic copy of the biological sample encoding the promoter of the prostate specific antigen, wherein the presence of at least one detected mutation is diagnostic for increased levels of PSA in the subject, and wherein said mutation occurs at position 4643, 5307, 5412 or 5429 in the promoter of the prostate specific antigen gene.    
     
     
         23 . The method of  claim 22 , wherein the promoter of the PSA comprises a sequence from an androgen responsive element III.  
     
     
         24 . The method of  claim 22 , wherein said mutation at position 4643 is G4643A.  
     
     
         25 . The method of  claim 22 , wherein said mutation at position 5307 is G5307A.  
     
     
         26 . The method of  claim 22 , wherein said mutation at position 5412 is C5412T.  
     
     
         27 . The method of  claim 22 , wherein said mutation at position 5429 is T5429G.  
     
     
         28 . The method of  claim 22 , wherein said method of screening for increased PSA levels comprises screening for an increased risk of prostate cancer.  
     
     
         29 . A nucleic acid molecule encoding an androgen responsive element III having a mutation that is associated with prostate cancer, wherein said mutation at position 4643, 5307, 5412 or 5429 in the promoter of the prostate specific antigen gene.  
     
     
         30 . An oligonucleotide of from 5 to 50 bases that hybridizes to a nucleic acid of  claim 29 .  
     
     
         31 . A method for detecting the presence of a genetic polymorphism associated with an androgen responsive element III in a sample of patient nucleic acid, comprising: 
 amplifying an androgen responsive promoter element gene sequence in the patient nucleic acid to produce an amplification product; and    identifying the presence of a genetic predisposition for increased cellular PSA production with the amplification product.