Table 5 UGT1A/DPYD polymorphisms and clinical response
Genotype | Single IRI ± targeted therapy | IRI + fluorouracill ± targeted therapy | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
First line treatment | ≧Second line treatment | First line treatment | ≧Second line treatment | |||||||||||||
ORR | P value | DCR | P value | ORR | P value | DCR | P value | ORR | P value | DCR | P value | ORR | P value | DCR | P value | |
Sex | ||||||||||||||||
 Male | 0/1 (0.0%) | 1/1 (100.0%) | 0/29 (0.0%) | 18/29 (62.1%) | 17/56 (30.4%) | 49/56 (87.5%) | 39/295 (13.2%) | 235/295 (79.7%) | ||||||||
 Female | 1/3 (33.3%) | 1.000 | 2/3 (67.7%) | 1.000 | 4/34 (11.8%) | 0.118 | 19/34 (55.9%) | 0.619 | 12/33 (36.4%) | 0.559 | 29/33 (87.9%) | 0.958 | 23/183 (12.6%) | 0.837 | 141/183 (77.0%) | 0.498 |
Age | ||||||||||||||||
≦65y | 1/3 (33.3%) | 2/3 (66.7%) | 4/42 (9.5%) | 28/42 (66.7%) | 28/80 (35.0%) | 71/80 (88.8%) | 56/398 (14.1%) | 317/398 (79.6%) | ||||||||
 >65y | 0/1 (0.0%) | 1.000 | 1/1 (100.0%) | 1.000 | 0/21 (0.0%) | 0.292 | 9/21 (42.9%) | 0.070 | 1/9 (11.1%) | 0.216 | 7/9 (77.8%) | 0.343 | 6/80 (7.5%) | 0.11 | 59/80 (73.8%) | 0.24 |
Primary tumor location | ||||||||||||||||
 Left-side colorectum | 1/3 (33.3%) | 2/3 (66.7%) | 3/43 (7.0%) | 27/43 (62.8%) | 20/60 (33.3%) | 54/69 (90.0%) | 47/362 (13.0%) | 289/362 (79.8%) | ||||||||
 Right-side colon | 0/1 (0.0%) | 1.000 | 1/1 (100.0%) | 1.000 | 1/20 (5.0%) | 1.000 | 10/20 (50.0%) | 0.337 | 9/29 (31.0%) | 0.828 | 24/29 (82.8%) | 0.331 | 15/116 (12.9%) | 0.988 | 87/116 (75.0%) | 0.269 |
UGT1A1*6 | ||||||||||||||||
 G/G | 1/4 (25.0%) | 3/4 (75.0%) | 3/46 (6.5%) | 28/46 (60.9%) | 17/54 (31.5%) | 49/54 (90.7%) | 42/310 (13.5%) | 239/301 (77.1%) | ||||||||
 G/A | 0/0 (0.0%) | 0/0 (0.0%) | 1/15 (6.7%) | 7/15 (46.7%) | 9/31 (29.0%) | 25/31 (80.6%) | 16/145 (11.0%) | 119/145 (82.1%) | ||||||||
 A/A | 0/0 (0.0%) | NA | 0/0 (0.0%) | NA | 0/2 (0.0%) | 0.932 | 2/2 (100.0%) | 0.302 | 3/4 (75%) | 0.175 | 4/4 (100.0%) | 0.295 | 4/23 (17.4%) | 0.615 | 18/23 (78.3%) | 0.483 |
UGT1A1*27 | ||||||||||||||||
 C/A | 0/0 (0.0%) | 0/0 (0.0%) | 3/43 (7.0%) | 28/43 (65.1%) | 2/3 (66.7%) | 2/3 (66.7%) | 54/387 (14.0%) | 313/387 (80.9%) | ||||||||
 C/C | 1/2 (50.0%) | NA | 2/2 (100.0%) | NA | 0/0 (0.0%) | NA | 0/0 (0.0%) | NA | 26/84 (31.0%) | 0.193 | 74/84 (88.1%) | 0.272 | 0/7 (0.0%) | 0.600 | 6/7 (85.7%) | 0.747 |
UGT1A1*28 | ||||||||||||||||
 TA6/TA6 | 1/3 (33.3%) | 2/3 (66.7%) | 4/48 (8.3%) | 29/48 (60.4%) | 15/59 (25.4%) | 52/59 (88.1%) | 53/373 (14.2%) | 293/373 (78.6%) | ||||||||
 TA6/TA7,TA7/TA7 | 0/1 (0.0%) | 1.000 | 1/1 (100.0%) | 1.000 | 0/15 (0.0%) | 0.564 | 8/15 (53.3%) | 0.627 | 14/30 (46.7%) | 0.043 | 26/30 (86.7%) | 0.842 | 9/105 (8.6%) | 0.129 | 83/105 (79.0%) | 0.913 |
UGT1A7 | ||||||||||||||||
  UGT1A7*1/*1,*1/*2,*2/*2 | 1/2 (50.0%) | 2/2 (100.0%) | 3/32 (9.4%) | 20/32 (62.5%) | 12/47 (25.5%) | 42/47 (89.4%) | 35/241 (14.5%) | 194/241 (80.5%) | ||||||||
  UGT1A7*1/*3,*2/*3,*3/*3 | 0/0 (0.0%) | 0.558 | 0/0 (0.0%) | NA | 0/11 (0.0%) | 0.558 | 8/11 (72.7%) | 0.539 | 15/38 (39.5%) | 0.17 | 32/38 (84.2%) | 0.482 | 19/153 (12.4%) | 0.554 | 125/153 (81.7%) | 0.767 |
UGT1A9*22 | ||||||||||||||||
 T9/T9 | 0/0 (0.0%) | 0/0 (0.0%) | 0/8 (0.0%) | 5/8 (62.5%) | 6/13 (46.2%) | 11/13 (84.6%) | 5/71 (7.0%) | 61/71 (85.9%) | ||||||||
 T9/T10,T10/T10 | 1/2 (50.0%) | 1.000 | 2/2 (100.0%) | NA | 3/35 (8.6%) | 1.000 | 23/35 (65.7%) | 0.863 | 21/72 (29.2%) | 0.226 | 63/72 (87.5%) | 0.776 | 49/323 (15.2%) | 0.071 | 258/323 (79.9%) | 0.241 |
DPYD*5 | ||||||||||||||||
 A/A | NA | NA | NA | NA | 8/41 (19.5%) | 34/41 (82.9%) | 32/211 (15.2%) | 174/211 (82.5%) | ||||||||
 A/G,G/G | NA | NA | NA | NA | NA | NA | NA | NA | 19/44 (43.2%) | 0.019 | 40/44 (90.9%) | 0.273 | 22/183 (12.0%) | 0.365 | 145/183 (79.2%) | 0.415 |
DPYD c.1896 T > C | ||||||||||||||||
 T/T | NA | NA | NA | NA | 24/69 (34.8%) | 60/69 (87.0%) | 42/314 (13.4%) | 254/314 (80.9%) | ||||||||
 T/T,T/C | NA | NA | NA | NA | NA | NA | NA | NA | 3/16 (18.8%) | 0.215 | 14/16 (87.5%) | 0.953 | 12/80 (15.0%) | 0.706 | 65/80 (81.3%) | 0.942 |