Background
Methods
Study population
Immunohistochemistry
SNP selection
RS number | Gene | Alleles (major > minor) | Position in gene and functionality | Clinical influence of polymorphism |
---|---|---|---|---|
rs10735380 |
IGF1
| A > G | Transcription factor binding site, intronic | |
rs1520220 |
IGF1
| C > G | Intronic | |
rs6220 |
IGF1
| A > G | 3′-untranslated region, microRNA binding site | Variant G allele associated with increased serum IGF-1 level and increased BC risk [42] |
rs2946834 |
IGF1
| G > A | 3′-untranslated region | |
rs2270628 |
IGFBP3
| C > T | Downstream | |
rs2854746 |
IGFBP3
| G > C | Nonsynonymous in exon 1 | |
(Ala32Gly) | ||||
rs4320932 |
IGF2
| T > C | Transcription factor binding site, intronic | Variant C allele associated with worse outcome in ovarian cancer and worse response to CT [45] |
rs2016347 |
IGF1R
| G > T | 3′-untranslated region, microRNA binding site | Variant T allele associated with better outcome in ER+ BC [22] |
DNA isolation and preamplification
Statistical analysis
Results
Patient characteristics
Patients (N = 216) in NEOZOTAC | ||
---|---|---|
Median age, years (range) | 49.5 (28–70) | |
Median BMI, kg/m2 (range) | 26.2 (18.3–42.0) | |
Clinical T stage | cT1 or cT2 | 123 (56.9 %) |
cT3 or cT4 | 93 (43.1 %) | |
Clinical N stage | cN0 | 101 (46.8 %) |
cN+ | 115 (53.2 %) | |
Tumor type | Ductal | 128 (59.3 %) |
Lobular | 38 (17.6 %) | |
Other | 18 (8.4 %) | |
Unknown | 32 (14.8 %) | |
HR status | ER+ and/or PR+ | 180 (83.3 %) |
ER– and PR– | 36 (16.7 %) | |
Allocated treatment | TAC | 109 (50.5 %) |
TAC + ZA | 107 (49.5 %) | |
pCR breast and LN | Yes | 25 (11.6 %) |
No | 184 (85.2 %) | |
Unknown | 7 (3.2 %) | |
MP breast | 1 | 33 (15.3 %) |
2 | 56 (25.9 %) | |
3 | 41 (19.0 %) | |
4 | 42 (19.4 %) | |
5 | 35 (16.2 %) | |
Unknown | 9 (4.2 %) |
IGF-1R expression
IGF-1R pathway SNPs
SNP | Allele |
N = 184 (%) | HWE χ2
|
P value | Call rate (%) |
---|---|---|---|---|---|
rs10735380 | AA | 110 (54.3) | 2.1 | 0.144 | 94 |
IGF1
| AG | 68 (37.0) | |||
GG | 5 (2.7) | ||||
NE | 11 (6.0) | ||||
rs1520220 | CC | 115 (62.5) | 4.4 | 0.040a
| 94 |
IGF1
| CG | 46 k | |||
GG | 11 (6.0) | ||||
NE | 12 (6.5) | ||||
rs6220 | AA | 91 (49.5) | 3.3 | 0.068 | 89 |
IGF1
| AG | 56 (30.4) | |||
GG | 17 (9.2) | ||||
NE | 20 (10.9) | ||||
rs2946834b
| GG | 82 (44.6) | 10.1 | 0.001a
| 88 |
IGF1
| GA | 53 (28.8) | |||
AA | 26 (14.1) | ||||
NE | 23 (12.5) | ||||
rs2270628 | CC | 105 (57.1) | 2.8 | 0.096 | 87 |
IGFBP3
| CT | 45 (24.5) | |||
TT | 10 (5.4) | ||||
NE | 24 (13.0) | ||||
rs2854746 | GG | 59 (32.1) | 1.9 | 0.170 | 90 |
IGFBP3
| GC | 72 (39.1) | |||
CC | 34 (18.5) | ||||
NE | 19 (10.3) | ||||
rs4320932 | TT | 111 (60.3) | 0.04 | 0.843 | 96 |
IGF2
| TC | 57 (31) | |||
CC | 8 (4.3) | ||||
NE | 8 (4.3) | ||||
rs2016347 | GG | 48 (26.1) | 1.8 | 0.185 | 96 |
IGF1R
| GT | 96 (52.2) | |||
TT | 32 (17.4) | ||||
NE | 8 (4.3) |
Univariate analysis | Multivariate analysis | ||||||||
---|---|---|---|---|---|---|---|---|---|
Parameter |
N
| % pCR | OR | 95 % CI |
P value | OR | 95 % CI |
P value | |
Clinical T stage | cT1/cT2 | 106 | 17.9 | 1 | Reference | 1 | Reference | ||
cT3/T4 | 73 | 6.8 | 0.34 | 0.12–0.95 | 0.039 | 0.49 | 0.16–1.50 | 0.209 | |
Clinical N stage | cN0 |
84
| 21.4 | 1 | Reference | 1 | Reference | ||
cN+ |
95
| 6.3 | 0.25 | 0.09–0.66 | 0.005 | 0.19 | 0.06–0.58 | 0.003 | |
HR status | ER+ and/or PR+ | 151 | 8.6 | 1 | Reference | 1 | Reference | ||
Triple negative | 28 | 39.3 | 6.87 | 2.66–17.7 | 0.00007 | 9.35 | 3.09–28.3 | 0.00008 | |
Allocated treatment | TAC + ZA | 87 | 14.9 | 1 | Reference | 0.559 | |||
TAC only | 92 | 12.0 | 0.77 | 0.33–1.83 | |||||
Age | 0.96 | 0.89–1.09 | 0.186 | ||||||
BMI | 0.97 | 0.88–1.08 | 0.581 | ||||||
rs10735380 | AA | 97 | 13.4 | 1 | Reference | ||||
IGF1
| AG | 66 | 13.6 | 1.02 | 0.41–2.55 | 0.966 | |||
GG | 5 | 20.0 | 1.61 | 0.17–15.6 | 0.679 | ||||
rs1520220 | CC | 111 | 15.3 | 1 | Reference | ||||
IGF1
| CG | 45 | 13.3 | 0.85 | 0.31–2.32 | 0.752 | |||
GG | 11 | 0.0 | – | – | – | ||||
rs6220 | AA | 88 | 11.4 | 1 | Reference | ||||
IGF1
| AG | 56 | 16.1 | 1.49 | 0.57–3.94 | 0.418 | |||
GG | 17 | 17.6 | 1.67 | 0.41–6.48 | 0.475 | ||||
rs2270628 | CC | 101 | 11.9 | 1 | Reference | ||||
IGFBP3
| CT | 45 | 17.8 | 1.60 | 0.61–4.24 | 0.342 | |||
TT | 9 | 0.0 | – | – | – | ||||
rs2854746 | GG | 55 | 7.3 | 1 | Reference | 1 | Reference | ||
IGFBP3
| GC | 72 | 16.7 | 2.55 | 0.78–8.40 | 0.124 | 3.06 | 0.82–11.4 | 0.097 |
CC | 33 | 21.2 | 3.43 | 0.92–12.8 | 0.066 | 4.02 | 0.92–17.6 | 0.065 | |
GG | 55 | 7.3 | 1 | Reference | 1 | Reference | |||
GC/CC | 105 | 18.1 | 2.82 | 0.91–8.74 | 0.073 | 3.35 | 0.96–11.7 | 0.058 | |
rs4320932 | TT | 106 | 15.1 | 1 | Reference | ||||
IGF2
| TC | 57 | 12.3 | 0.79 | 0.30–2.04 | 0.623 | |||
CC | 8 | 12.5 | 0.80 | 0.09–6.98 | 0.843 | ||||
rs2016347 | GG | 45 | 4.4 | 1 | Reference | 1 | Reference | ||
IGF1R
| GT | 94 | 17.0 | 4.41 | 0.97–20.1 | 0.055 | 5.58 | 1.08–28.7 | 0.040 |
TT | 32 | 15.6 | 3.98 | 0.72–22.0 | 0.113 | 6.67 | 1.03–43.1 | 0.046 | |
GG | 45 | 4.4 | 1 | Reference | 1 | Reference | |||
GT/TT | 126 | 16.7 | 4.30 | 1.00–19.1 | 0.056 | 5.82 | 1.17–29.1 | 0.032 |