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Table 5 UGT1A/DPYD polymorphisms and clinical response

From: Examination of multiple UGT1A and DPYD polymorphisms has limited ability to predict the toxicity and efficacy of metastatic colorectal cancer treated with irinotecan-based chemotherapy: a retrospective analysis

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
  1. IRI: Irinotecan; ORR: Objective response rate; DCR: Disease control rate; Tumor location: Left-side colorectum included splenic flexure, descending colon, sigmoid colon and rectum; Right-side colon included cecum, ascending and transverse colon [18]; NA: Non-acquired