Table 2.
Gene locations and association with prostate cancer aggressiveness and efficiency of androgen deprivation therapy
| Gene/SNP | Frequency | Location | OR (95% CI) |
HR (95% CI) |
||
|---|---|---|---|---|---|---|
| Age at diagnosis, ≤60 y vs. >60 y | D'Amico risk class, high/intermediate vs. low | Pathologic stages, advanced vs. localized | Patients on ADT | |||
| (n = 4,073) | (n = 3,938) | (n = 3,347) | (n = 1,716) | (n = 553) | ||
| AR | ||||||
| rs1204038 | Intron 1 | P = 0.04 | P = 0.38 | P = 0.81 | P = 0.86 | |
| G | 84.8% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| A | 15.2% | 1.22 (1.01-1.47) | 1.11 (0.88-1.40) | 0.96 (0.70-1.32) | 1.03 (0.75-1.40) | |
| rs2361634 | Intron 1 | P = 0.68 | P = 0.95 | P = 0.94 | P = 0.67 | |
| A | 93.7% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| G | 6.3% | 1.06 (0.82-1.37) | 1.01 (0.74-1.37) | 1.02 (0.67-1.54) | 0.93 (0.65-1.32) | |
| rs5919411 | Intron 3 | P = 0.38 | P = 0.37 | P = 0.22 | P = 0.66 | |
| G | 93.3% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| A | 6.7% | 1.12 (0.87-1.44) | 1.15 (0.85-1.56) | 0.77 (0.51-1.17) | 0.91 (0.59-1.40) | |
| rs12011518 | Intron 4 | P = 0.69 | P = 0.96 | P = 0.80 | P = 0.08 | |
| G | 92.5% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| T | 7.5% | 1.05 (0.83-1.33) | 1.01 (0.75-1.35) | 1.05 (0.70-1.58) | 0.75 (0.50-1.12) | |
| ESR1 | ||||||
| rs6935443 | Near 5′ | P = 0.33 | P = 0.87 | P = 0.30 | P = 0.79 | |
| AA | 66.0% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG/GG | 34.0% | 0.94 (0.82-1.07) | 1.01 (0.86-1.19) | 1.12 (0.90-1.40) | 0.97 (0.78-1.21) | |
| rs9478244 | Near 5′ | P = 0.46 | P = 0.57 | P = 0.37 | P = 0.51 | |
| AA | 66.9% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG/GG | 33.1% | 0.95 (0.83-1.09) | 1.05 (0.89-1.23) | 1.10 (0.89-1.37) | 1.08 (0.86-1.34) | |
| rs2077647 | Exon 1(S10S) | P = 0.01 | P = 0.84 | P = 0.03 | P = 0.02 | |
| TT | 26.8% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT | 48.4% | 0.81 (0.70-0.95) | 1.01 (0.84-1.22) | 0.74 (0.57-0.95) | 1.34 (1.04-1.73) | |
| CC | 24.8% | 0.96 (0.80-1.15) | 1.07 (0.87-1.33) | 0.72 (0.54-0.97) | 0.99 (0.74-1.33) | |
| rs532010 | Intron 1 | P = 0.08 | P = 0.63 | P = 0.04 | P = 0.14 | |
| GG | 35.6% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 48.5% | 0.86 (0.72-1.03) | 1.01 (0.81-1.25) | 1.13 (0.83-1.52) | 1.25 (0.92-1.70) | |
| AA | 15.9% | 0.99 (0.83-1.20) | 0.95 (0.76-1.19) | 1.41 (1.03-1.93) | 1.02 (0.74-1.41) | |
| rs17081698 | Intron 1 | P = 0.62 | P = 0.60 | P = 0.61 | P = 0.31 | |
| TT | 81.1% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| GT/GG | 18.9% | 1.04 (0.89-1.22) | 0.95 (0.79-1.15) | 0.93 (0.72-1.22) | 0.87 (0.66-1.14) | |
| rs9340788 | Intron 1 | P = 0.95 | P = 0.53 | P = 0.64 | P = 0.22 | |
| CC | 90.4% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AC/AA | 9.6% | 0.99 (0.80-1.24) | 0.92 (0.71-1.19) | 1.09 (0.77-1.54) | 1.27 (0.87-1.85) | |
| rs17081749 | Intron 1 | P = 0.005 | P = 0.93 | P = 0.68 | P = 0.16 | |
| TT | 76.6% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| GT/GG | 23.4% | 0.81 (0.70-0.94) | 1.01 (0.84-1.20) | 0.95 (0.75-1.21) | 1.19 (0.93-1.51) | |
| rs6902771 | Intron 1 | P = 0.01 | P = 0.87 | P = 0.01 | P = 0.53 | |
| TT | 29.8% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT | 48.9% | 0.81 (0.69-0.95) | 0.93 (0.76-1.13) | 1.01 (0.77-1.32) | 1.11 (0.85-1.46) | |
| CC | 21.3% | 1.01 (0.85-1.20) | 0.93 (0.75-1.15) | 1.37 (1.03-1.83) | 0.98 (0.73-1.32) | |
| rs3936674 | Intron 2 | P = 0.65 | P = 0.35 | P = 0.01 | P = 0.28 | |
| GG | 43.6% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 45.4% | 0.94 (0.82-1.07) | 1.12 (0.95-1.31) | 0.86 (0.69-1.07) | 1.18 (0.95-1.47) | |
| AA | 11.0% | 0.77 (0.79-1.20) | 1.14 (0.88-1.47) | 0.61 (0.43-0.89) | 0.99 (0.68-1.43) | |
| rs712221 | Intron 2 | P = 0.90 | P = 0.73 | P = 0.09 | P = 0.85 | |
| TT | 19.0% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AT | 48.2% | 1.02 (0.86-1.20) | 0.95 (0.77-1.17) | 1.20 (0.90-1.60) | 1.06 (0.80-1.40) | |
| AA | 32.8% | 0.98 (0.82-1.18) | 0.90 (0.73-1.13) | 1.32 (0.97-1.79) | 1.00 (0.75-1.35) | |
| rs1643821 | Intron 2 | P = 0.94 | P = 0.66 | P = 0.18 | P = 0.43 | |
| GG | 33.3% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 47.8% | 1.03 (0.89-1.18) | 1.09 (0.92-1.29) | 0.98 (0.78-1.24) | 1.16 (0.92-1.46) | |
| AA | 18.9% | 1.02 (0.85-1.22) | 1.08 (0.87-1.34) | 0.80 (0.59-1.08) | 1.04 (0.77-1.40) | |
| rs7761846 | Intron 3 | P = 0.18 | P = 0.29 | P = 0.26 | P = 0.22 | |
| TT | 87.1% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT/CC | 12.9% | 0.88 (0.73-1.06) | 1.13 (0.90-1.43) | 1.19 (0.88-1.61) | 0.82 (0.60-1.12) | |
| rs2347923 | Intron 3 | P = 0.46 | P = 0.31 | P = 0.52 | P = 0.91 | |
| CC | 9.2% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AC | 42.5% | 1.15 (0.91-1.44) | 0.87 (0.66-1.15) | 1.13 (0.77-1.64) | 1.00 (0.69-1.44) | |
| AA | 48.3% | 1.15 (0.92-1.44) | 0.99 (0.75-1.30) | 0.96 (0.66-1.39) | 1.04 (0.72-1.51) | |
| rs1514347 | Intron 3 | P = 0.35 | P = 0.41 | P = 0.27 | P = 0.88 | |
| TT | 5.7% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT | 35.0% | 1.06 (0.80-1.43) | 1.00 (0.70-1.41) | 0.92 (0.58-1.48) | 0.97 (0.63-1.49) | |
| CC | 59.3% | 0.96 (0.73-1.28) | 1.10 (0.78-1.54) | 0.78 (0.49-1.23) | 0.93 (0.61-1.40) | |
| rs2347867 | Intron 3 | P = 0.62 | P = 0.85 | P = 0.16 | P = 0.85 | |
| GG | 11.3% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 44.5% | 0.92 (0.74-1.14) | 0.92 (0.71-1.20) | 1.09 (0.78-1.54) | 0.99 (0.71-1.38) | |
| AA | 44.2% | 0.90 (0.73-1.11) | 0.98 (0.74-1.25) | 0.86 (0.61-1.23) | 1.06 (0.76-1.48) | |
| rs2347868 | Intron 3 | P = 0.65 | P = 0.25 | P = 0.29 | P = 0.90 | |
| TT | 5.5% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT | 35.0% | 1.10 (0.82-1.48) | 0.91 (0.64-1.51) | 1.02 (0.64-1.63) | 0.98 (0.62-1.55) | |
| CC | 59.5% | 1.04 (0.78-1.39) | 1.04 (0.73-1.48) | 0.85 (0.54-1.35) | 0.94 (0.60-1.46) | |
| rs6912184 | Intron 3 | P = 0.20 | P = 0.09 | P = 0.84 | P = 0.94 | |
| GG | 5.9% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 34.5% | 1.29 (0.97-1.70) | 0.92 (0.65-1.30) | 0.89 (0.56-1.40) | 1.08 (0.70-1.65) | |
| AA | 59.6% | 1.27 (0.97-1.67) | 1.09 (0.78-1.53) | 0.86 (0.55-1.34) | 1.07 (0.71-1.62) | |
| rs9371564 | Intron 3 | P = 0.60 | P = 0.62 | P = 0.76 | P = 0.87 | |
| GG | 44.0% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 44.7% | 1.00 (0.88-1.14) | 0.93 (0.79-1.09) | 1.12 (0.90-1.40) | 1.02 (0.82-1.27) | |
| AA | 11.3% | 0.91 (0.74-1.11) | 0.91 (0.71-1.17) | 1.06 (0.76-1.50) | 0.93 (0.67-1.30) | |
| rs3020401 | Intron 4 | P = 0.70 | P = 0.49 | P = 0.24 | P = 0.92 | |
| GG | 11.4% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 45.0% | 0.99 (0.81-1.22) | 1.16 (0.90-1.49) | 0.89 (0.64-1.24) | 0.98 (0.71-1.36) | |
| AA | 43.6% | 0.94 (0.77-1.16) | 1.13 (0.88-1.45) | 0.76 (0.54-1.06) | 0.94 (0.68-1.31) | |
| rs932480 | Intron 4 | P = 0.33 | P = 0.43 | P = 0.03 | P = 0.60 | |
| GT/TT | 32.5% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| GG | 67.5% | 0.94 (0.82-1.07) | 0.94 (0.80-1.10) | 0.79 (0.63-0.98) | 0.95 (0.76-1.18) | |
| rs1884052 | Intron 4 | P = 0.64 | P = 0.68 | P = 0.05 | P = 0.71 | |
| CG/GG | 27.9% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CC | 72.1% | 0.97 (0.84-1.11) | 1.04 (0.88-1.22) | 0.80 (0.64-1.00) | 0.96 (0.76-1.20) | |
| rs726281 | Intron 4 | P = 0.29 | P = 0.54 | P = 0.37 | P = 0.78 | |
| GG | 8.2% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 38.9% | 0.83 (0.65-1.06) | 1.00 (0.74-1.34) | 0.88 (0.61-1.28) | 0.91 (0.64-1.30) | |
| AA | 52.9% | 0.84 (0.66-1.06) | 0.92 (0.69-1.22) | 0.78 (0.54-1.12) | 0.98 (0.69-1.39) | |
| rs9397463 | Intron 4 | P = 0.88 | P = 0.16 | P = 0.90 | P = 0.29 | |
| CT/TT | 26.7% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CC | 73.3% | 0.99 (0.86-1.14) | 0.89 (0.75-1.05) | 0.97 (0.77-1.23) | 1.13 (0.90-1.43) | |
| rs9340954 | Intron 4 | P = 0.16 | P = 0.51 | P = 0.27 | P = 0.36 | |
| TT | 54.4% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| GT | 37.5% | 1.05 (0.92-1.20) | 1.08 (0.92-1.27) | 1.19 (0.96-1.49) | 0.96 (0.77-1.19) | |
| GG | 8.1% | 1.26 (0.99-1.59) | 1.18 (0.88-1.57) | 1.27 (0.89-1.81) | 1.27 (0.87-1.85) | |
| rs722208 | Intron 4 | P = 0.10 | P = 0.49 | P = 0.22 | P = 0.31 | |
| GG | 8.4% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 36.6% | 0.84 (0.65-1.06) | 0.87 (0.65-1.17) | 0.93 (0.64-1.33) | 0.74 (0.51-1.09) | |
| AA | 55.0% | 0.78 (0.62-0.99) | 0.82 (0.62-1.09) | 0.77 (0.54-1.09) | 0.78 (0.54-1.13) | |
| rs9340958 | Intron 4 | P = 0.22 | P = 0.51 | P = 0.98 | P = 0.11 | |
| CT/TT | 16.6% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CC | 83.4% | 0.90 (0.75-1.07) | 0.93 (0.76-1.15) | 0.96 (0.72-1.28) | 0.80 (0.62-1.05) | |
| rs9340978 | Intron 5 | P = 0.13 | P = 0.91 | P = 0.29 | P = 0.06 | |
| GG | 86.4% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG/AA | 13.6% | 1.16 (0.96-1.40) | 1.01 (0.81-1.27) | 1.17 (0.87-1.58) | 1.34 (1.00-1.80) | |
| rs6932864 | Intron 5 | P = 0.70 | P = 0.44 | P = 0.51 | P = 0.32 | |
| GG | 79.2% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG/AA | 20.8% | 1.03 (0.89-1.20) | 1.08 (0.89-1.30) | 1.09 (0.85-1.38) | 0.88 (0.69-1.13) | |
| rs3020371 | Intron 6 | P = 0.21 | P = 0.03 | P = 0.24 | P = 0.58 | |
| TT | 11.0% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT | 43.1% | 0.84 (0.68-1.05) | 1.05 (0.81-1.37) | 1.09 (0.78-1.54) | 0.83 (0.58-1.20) | |
| CC | 45.9% | 0.86 (0.69-1.07) | 0.85 (0.65-1.10) | 0.88 (0.62-1.24) | 0.82 (0.57-1.19) | |
| rs3778089 | Intron 6 | P = 0.63 | P = 0.37 | P = 0.85 | P = 0.71 | |
| GG | 78.8% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG/AA | 20.2% | 1.04 (0.89-1.21) | 1.09 (0.90-1.31) | 1.02 (0.80-1.31) | 0.95 (0.75-1.22) | |
| rs2982896 | Intron 6 | P = 0.93 | P = 0.06 | P = 0.11 | P = 0.32 | |
| CT/TT | 38.2% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CC | 61.8% | 1.00 (0.88-1.13) | 0.86 (0.74-1.01) | 0.83 (0.67-1.02) | 0.90 (0.73-1.11) | |
| rs2813545 | Near 3′ | P = 0.91 | P = 0.55 | P = 0.63 | P = 0.27 | |
| GG | 64.6% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CG/CC | 35.4% | 1.01 (0.88-1.15) | 1.05 (0.90-1.23) | 1.06 (0.85-1.31) | 0.89 (0.72-1.10) | |
| ESR2 | ||||||
| rs3020444 | Intron 1 | P = 0.92 | P = 0.54 | P = 0.84 | P = 0.84 | |
| AA | 40.9% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 44.7% | 1.03 (0.90-1.18) | 0.93 (0.79-1.10) | 1.08 (0.86-1.35) | 0.95 (0.70-1.27) | |
| GG | 14.4% | 1.00 (0.83-1.22) | 0.90 (0.71-1.13) | 1.10 (0.79-1.53) | 1.01 (0.75-1.37) | |
| rs10137185 | Intron 1 | P = 0.51 | P = 0.17 | P = 0.51 | P = 0.74 | |
| CC | 81.4% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT/TT | 18.6% | 1.06 (0.90-1.24) | 1.15 (0.91-1.39) | 0.92 (0.70-1.19) | 0.96 (0.74-1.23) | |
| rs1256033 | Intron 3 | P = 0.28 | P = 0.19 | P = 0.18 | P = 0.86 | |
| GG | 31.0% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AG | 48.6% | 0.99 (0.86-1.15) | 0.90 (0.76-1.07) | 0.96 (0.76-1.21) | 0.96 (0.75-1.22) | |
| AA | 20.4% | 0.88 (0.74-1.05) | 1.08 (0.86-1.33) | 0.78 (0.57-1.05) | 0.92 (0.69-1.23) | |
| rs1256044 | Intron 4 | P = 0.35 | P = 0.15 | P = 0.48 | P = 0.86 | |
| TT | 33.7% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT | 48.0% | 1.01 (0.88-1.16) | 0.90 (0.76-1.06) | 0.97 (0.77-1.22) | 0.98 (0.78-1.23) | |
| CC | 18.3% | 0.89 (0.75-1.07) | 1.08 (0.86-1.35) | 0.85 (0.62-1.15) | 0.92 (0.69-1.24) | |
| rs4986938 | Intron 8 | P = 0.59 | P = 0.91 | P = 0.04 | P = 0.10 | |
| TT | 15.8% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT | 47.1% | 1.04 (0.86-1.25) | 1.01 (0.81-1.26) | 1.13 (0.84-1.53) | 0.72 (0.53-0.98) | |
| CC | 37.1% | 0.97 (0.80-1.17) | 1.03 (0.82-1.30) | 0.83 (0.61-1.14) | 0.73 (0.53-1.00) | |
| rs8006145 | Intron 8 | P = 0.77 | P = 0.97 | P = 0.24 | P = 0.49 | |
| CC | 48.8% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| AC | 42.0% | 0.97 (0.85-1.11) | 1.02 (0.87-1.20) | 1.21 (0.97-1.51) | 1.05 (0.84-1.32) | |
| AA | 9.2% | 1.05 (0.83-1.32) | 0.99 (0.76-1.31) | 1.23 (0.84-1.78) | 1.26 (0.86-1.85) | |
| rs8018687 | Exon 9 (3′ UTR) | P = 0.51 | P = 0.62 | P = 0.20 | P = 0.52 | |
| TT | 86.3% | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | |
| CT/CC | 13.7% | 0.94 (0.78-1.13) | 0.95 (0.76-1.18) | 0.82 (0.60-1.11) | 0.90 (0.64-1.25) | |
Abbreviations: OR, odds ratio; HR, hazard ratio; 95% CI, 95% confidence interval; UTR, untranslated region.