Genetic Variations in ABCG2 Gene Predict Breast Carcinoma Susceptibility and Clinical Outcomes after Treatment with Anthracycline-Based Chemotherapy
Table 4
Multivariate COX regression analysis of ABCG2 genetic polymorphisms and patient clinicopathological features in association with DFS and OS in breast carcinoma patients with postoperative anthracycline-based chemotherapy.
Variable
DFS
OS
Total
Events (%)
Adjusted HR (95% CI)†
†
Total
Events (%)
Adjusted HR (95% CI) †
†
Patients with anthracycline-based chemotherapy
ABCG2 G34A
GG
340
70 (20.6)
1 (reference)
340
70 (20.6)
1 (reference)
GA
340
72 (21.2)
1.001 (0.718–1.395)
0.997
341
71 (20.9)
0.968 (0.694–1.349)
0.848
AA
81
14 (17.3)
0.777 (0.570–1.059)
0.111
81
12 (14.8)
0.709 (0.507–0.991)
0.044
ABCG2 C421A
CC
367
83 (22.6)
1 (reference)
367
80 (21.8)
1 (reference)
CA
310
60 (19.4)
0.930 (0.665–1.301)
0.673
311
60 (19.4)
1.010 (0.719–1.418)
0.956
AA
84
13 (15.5)
0.900 (0.706–1.147)
0.395
84
13 (15.5)
0.951 (0.745–1.213)
0.685
ER positive patients with anthracycline-based chemotherapy
ABCG2 G34A
GG
200
43 (21.5)
1 (reference)
200
43 (21.5)
1 (reference)
GA
204
46 (22.5)
0.977 (0.639–1.492)
0.913
204
45 (22.1)
0.901 (0.591–1.375)
0.630
AA
40
7 (17.5)
0.646 (0.398–1.050)
0.078
40
5 (12.5)
0.496 (0.271–0.909)
0.023
ABCG2 C421A
CC
227
54 (23.8)
1 (reference)
227
51 (22.5)
1 (reference)
CA
163
34 (20.9)
1.098 (0.707–1.705)
0.679
163
34 (20.9)
1.230 (0.786–1.925)
0.364
AA
54
8 (14.8)
0.884 (0.606–1.288)
0.520
54
8 (14.8)
0.927 (0.635–1.355)
0.697
PR positive patients with anthracycline-based chemotherapy
ABCG2 G34A
GG
182
35 (19.2)
1 (reference)
182
35 (19.2)
1 (reference)
GA
200
43 (21.5)
1.103 (0.699–1.740)
0.674
200
42 (21.0)
1.025 (0.651–1.614)
0.916
AA
36
6 (16.7)
0.643 (0.373–1.110)
0.113
36
5 (13.9)
0.558 (0.302–1.029)
0.042
ABCG2 C421A
CC
216
49 (22.7)
1 (reference)
216
47 (21.8)
1 (reference)
CA
147
28 (19.0)
1.250 (0.783–1.995)
0.349
147
28 (19.0)
1.260 (0.783–2.027)
0.342
AA
55
7 (12.7)
0.797 (0.534–1.190)
0.267
55
7 (12.7)
0.840 (0.562–1.256)
0.395
Clinicopathological features
First-degree family history of cancer
No
927
207 (22.3)
1 (reference)
927
203 (21.9)
1 (reference)
Yes
242
53 (21.9)
0.899 (0.660–1.223)
0.497
242
51 (21.1)
0.912 (0.668–1.245)
0.562
Tumor size (cm)
≤2.0
430
79 (18.4)
1 (reference)
430
77 (17.9)
1 (reference)
>2.0
739
181 (24.5)
1.494 (1.143–1.953)
0.003
739
177 (18.2)
1.525 (1.164–1.999)
0.002
Clinical stages
I or II
670
90 (13.4)
1 (reference)
670
87 (13.0)
1 (reference)
III or IV
499
170 (34.1)
3.106 (2.392–4.032)
<0.001
499
167 (33.5)
3.092 (2.375–4.025)
<0.001
Lymph node metastasis status
Node-negative
632
94 (14.9)
1 (reference)
632
92 (14.6)
1 (reference)
Node-positive
537
166 (30.9)
2.331 (1.800–3.017)
<0.001
537
162 (30.2)
2.307 (1.778–2.994)
<0.001
HR: hazard ratio; 95% CI, 95% confidence interval; PFS: progression-free survival; RFS: recurrence-free survival; OS: overall survival; reference, reference category; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor; p53, tumor suppressor protein 53; BRCA1, breast carcinoma type 1 susceptibility protein; BRCA2, breast carcinoma type 2 susceptibility protein. † values and adjusted HR (95% CI) were assessed using multivariate Cox regression analysis adjusted for age and menopause status.
