Determining prostate cancer recurrence using polymorphisms in angiogenesis-related genes

Abstract

In particular, disclosed is a method for treating a patient with prostate cancer that involves genotyping a nucleic acid sample from the subject for one or more single nucleotide polymorphism (SNP) alleles in one or more genes angiogenesis, comparing the one or more SNP alleles to control allele frequencies to produce a SNP signature, and analyzing the SNP signature to generate a risk score. The risk score can represent the likelihood that the patient's prostate cancer will recur following radical prostatectomy. In particular embodiments, a high risk score in a patient with positive margins is an indication of a high risk of prostate cancer recurrence.

1 . A method for treating a patient with prostate cancer, comprising
 a) genotyping a nucleic acid sample from the subject for one or more single nucleotide polymorphism (SNP) alleles in angiogenesis genes selected from the group consisting of ANGPT1, CACNA1C, CDH12, CDH13, CDH6, COL4A3, DDI1, ELK3, FBLN1, FGF12, FGF2, FGFR2, FN1, HDAC3, ID3, IGF2, IL16, IL1A, IL6, ITGA9, ITGAV, ITGB2, ITGB3, LECT1, LZTS1, MAP3K7IP2, MMP15, MMP16, MMP28, NCOA3, NOS2, NRP1, P2RY5, PDGFRB, PGF, PTK2, ROBO1, RSPO3, SAMD14, STAB1, TEK, TFPI, TGFB2, THBS2, and TYR;   b) comparing the one or more SNP alleles to control allele frequencies to produce a SNP signature;   c) analyzing the SNP signature to generate a risk score;   d) prescribing adjuvant therapy if the patient has a high risk score for recurrence, and not prescribing adjuvant therapy if the patient has a low risk score for recurrence.   
     
     
         2 . The method of  claim 1 , wherein the patient has undergone radical prostatectomy. 
     
     
         3 . The method of  claim 2 , wherein the patient has positive margins after the radical prostatectomy. 
     
     
         4 . The method of  claim 1 , wherein step a) comprises genotyping the nucleic acid sample for at least 10 SNP alleles in the angiogenesis genes. 
     
     
         5 . The method of  claim 1 , wherein step a) comprises genotyping the nucleic acid sample for one or more SNP alleles at sites selected from the group consisting of rs1005666, rs10174098, rs1047100, rs10498214, rs1050779, rs10805564, rs10827227, rs10955455, rs1113283, rs11149598, rs1131445, rs11868894, rs1250248, rs13027749, rs13326165, rs1393350, rs1433168, rs1433172, rs1460924, rs1467251, rs1555025, rs1654680, rs16876215, rs17506789, rs1960669, rs198605, rs2069832, rs2071373, rs2143491, rs2152066, rs2173115, rs2359192, rs2429127, rs246394, rs2514864, rs267567, rs2796821, rs2912770, rs2912791, rs2916084, rs2981428, rs2981449, rs3209148, rs3759509, rs3768780, rs3783526, rs3788142, rs3842763, rs4416, rs4778641, rs4795090, rs684, rs7044842, rs7102675, rs7171517, rs722527, rs7625555, rs7742668, rs7839832, rs7871178, rs8034928, rs8176418, rs847690, rs859, rs889730, rs903999, rs9283851, and rs958614. 
     
     
         6 . The method of  claim 1 , wherein the SNP signature is analyzed by multivariate regression analysis or principal component analysis to calculate the risk score. 
     
     
         7 . The method of  claim 5 , wherein the patient has an elevated risk score if the nucleic acid sample comprises at least one (A) allele at rs1005666; at least one (A) allele at rs1047100; at least one (G) allele at rs10498214; at least one (C) allele at rs1050779; at least one (A) allele at rs1113283; at least one (G) allele at rs1131445; at least one (G) allele at rs11868894; at least one (C) allele at rs13027749; at least one (A) allele at rs13326165; at least one (A) allele at rs1393350; at least one (A) allele at rs1460924; at least one (A) allele at rs1467251; at least one (A) allele at rs1654680; at least one (A) allele at rs16876215; at least one (G) allele at rs17506789; at least one (A) allele at rs1960669; at least one (C) allele at rs198605; at least one (A) allele at rs2143491; at least one (A) allele at rs2152066; at least one (C) allele at rs2173115; at least one (A) allele at rs2359192; at least one (G) allele at rs2429127; at least one (A) allele at rs246394; at least one (A) allele at rs2514864; at least one (A) allele at rs267567; at least one (A) allele at rs2796821; at least one (C) allele at rs2912770; at least one (A) allele at rs2912791; at least one (A) allele at rs2916084; at least one (A) allele at rs2981449; at least one (A) allele at rs3209148; at least one (A) allele at rs3788142; at least one (G) allele at rs4778641; at least one (G) allele at rs4795090; at least one (A) allele at rs684; at least one (A) allele at rs7102675; at least one (A) allele at rs7171517; at least one (A) allele at rs722527; at least one (A) allele at rs7839832; at least one (G) allele at rs8034928; at least one (A) allele at rs8176418; at least one (G) allele at rs847690; at least one (G) allele at rs859; at least one (A) allele at rs903999; or any combination thereof. 
     
     
         8 . The method of  claim 5 , wherein the patient has a reduced risk score if the nucleic acid sample comprises at least one (G) allele at rs10174098; at least one (G) allele at rs10805564; at least one (A) allele at rs10827227; at least one (C) allele at rs10955455; at least one (A) allele at rs11149598; at least one (A) allele at rs1250248; at least one (G) allele at rs1433168; at least one (A) allele at rs1433172; at least one (A) allele at rs1555025; at least one (A) allele at rs2069832; at least one (G) allele at rs2071373; at least one (A) allele at rs2981428; at least one (A) allele at rs3759509; at least one (A) allele at rs3768780; at least one (A) allele at rs3783526; at least one (A) allele at rs3842763; at least one (A) allele at rs4416; at least one (A) allele at rs7044842; at least one (G) allele at rs7625555; at least one (G) allele at rs7742668; at least one (A) allele at rs7871178; at least one (G) allele at rs889730; at least one (G) allele at rs9283851; at least one (C) allele at and rs958614; or any combination thereof.