Background
Methods
Patient material; cases and controls
Blood sampling
Phenotypic hemostatic parameters
DNA isolation and genotyping
SNP selection and quality control
Statistical methods
Results
Associations between SNPs in TF pathway genes and risk of breast cancer
Gene | Chr | SNP | Bp (hg18) | Region | Minor allele | Major allele | Freqency cases | Frequency controls | χ2
| OR |
P-value (unadj.) | FDR |
---|---|---|---|---|---|---|---|---|---|---|---|---|
F2
| 11 | rs2070852 | 46701501 | Intronic | C | G | 0.290 | 0.316 | 0.99 | 0.89 | 0.319 | 0.83 |
F2
| 11 | rs3136516 | 46717332 | Intronic | G | A | 0.448 | 0.448 | 0.00 | 1.00 | 0.996 | 1.00 |
F2
| 11 | rs5896 | 46701579 | Coding (T > M) | T | C | 0.133 | 0.127 | 0.09 | 1.05 | 0.760 | 0.93 |
F2
| 11 |
rs1799963
|
46717631
|
3UTR
|
A
|
G
|
0.013
|
0.005
|
2.20
|
2.60
|
0.138
|
0.61
|
F3
| 1 | rs3917643 | 94774455 | Intronic | C | T | 0.058 | 0.080 | 2.58 | 0.70 | 0.109 | 0.57 |
F3
| 1 | rs696619 | 94777808 | Intronic | A | G | 0.414 | 0.440 | 0.87 | 0.90 | 0.351 | 0.83 |
F3
| 1 | rs1324214 | 94769876 | Intronic | A | G | 0.240 | 0.271 | 1.59 | 0.85 | 0.207 | 0.70 |
F3
| 1 | rs3917615 | 94774578 | Intronic | T | C | 0.439 | 0.433 | 0.04 | 1.02 | 0.839 | 0.93 |
F5
|
1
|
rs12120605
|
167789178
|
Intronic
|
T*
|
G
|
0.140
|
0.100
|
4.93
|
1.47
|
0.026
|
0.22
|
F5
|
1
|
rs6427202
|
167795454
|
Intronic
|
C*
|
T
|
0.454
|
0.394
|
4.82
|
1.28
|
0.028
|
0.22
|
F5
|
1
|
rs9332542
|
167805907
|
Intronic
|
A
|
G*
|
0.286
|
0.344
|
5.16
|
0.76
|
0.023
|
0.22
|
F5
|
1
|
rs6427199
|
167790161
|
Intronic
|
A
|
G*
|
0.364
|
0.420
|
4.36
|
0.79
|
0.037
|
0.23
|
F5
| 1 | rs6012 | 167795204 | Intronic | T | C | 0.162 | 0.164 | 0.01 | 0.98 | 0.906 | 0.93 |
F5
| 1 | rs4524 | 167778379 | Coding (K > R) | C | T | 0.261 | 0.257 | 0.03 | 1.02 | 0.871 | 0.93 |
F5
| 1 | rs4656687 | 167771782 | Intronic | C | T | 0.323 | 0.312 | 0.17 | 1.05 | 0.676 | 0.93 |
F5
| 1 |
rs6025
|
167785673
|
Coding (Q > R)
|
T
|
C
|
0.033
|
0.034
|
0.02
|
0.96
|
0.900
|
0.93
|
F5
| 1 | rs9287095 | 167805090 | Intronic | A | G | 0.094 | 0.104 | 0.34 | 0.90 | 0.561 | 0.93 |
F5
| 1 | rs10158595 | 167786988 | Intronic | T | C | 0.223 | 0.248 | 1.14 | 0.87 | 0.286 | 0.83 |
F5
| 1 | rs9332618 | 167767105 | Intronic | A | G | 0.133 | 0.139 | 0.08 | 0.95 | 0.773 | 0.93 |
F7
| 13 | rs491098 | 112817347 | Intronic | C | G | 0.106 | 0.117 | 0.39 | 0.90 | 0.530 | 0.93 |
F10
|
13
|
rs3093261
|
112824083
|
Near 5UTR
|
T*
|
C
|
0.460
|
0.391
|
6.41
|
1.33
|
0.011
|
0.22
|
F10
| 13 | rs3211744 | 112832999 | Intronic | T | G | 0.136 | 0.154 | 0.85 | 0.87 | 0.358 | 0.83 |
F10
| 13 | rs2026160 | 112840894 | Intronic | C | A | 0.284 | 0.258 | 1.08 | 1.14 | 0.298 | 0.83 |
F10
| 13 | rs9549675 | 112846885 | Intronic | T | C | 0.205 | 0.239 | 2.10 | 0.83 | 0.148 | 0.61 |
F10
| 13 | rs3211719 | 112825510 | Intronic | G | A | 0.252 | 0.245 | 0.09 | 1.04 | 0.769 | 0.93 |
F10
| 13 | rs3211752 | 112835460 | Intronic | G | A | 0.499 | 0.489 | 0.13 | 1.04 | 0.716 | 0.93 |
F10
| 13 | rs556694 | 112828042 | Intronic | C | T | 0.093 | 0.089 | 0.04 | 1.04 | 0.836 | 0.93 |
F10
| 13 | rs3211770 | 112841850 | Intronic | A | G | 0.109 | 0.113 | 0.05 | 0.96 | 0.818 | 0.93 |
F10
| 13 | rs473598 | 112849190 | Intronic | A | G | 0.128 | 0.137 | 0.23 | 0.92 | 0.629 | 0.93 |
EPCR
|
20
|
rs2069948
|
33226150
|
Intronic
|
C*
|
T
|
0.468
|
0.408
|
4.72
|
1.27
|
0.030
|
0.22
|
TFPI
| 2 | rs2192825 | 188099064 | Intronic | C | T | 0.439 | 0.402 | 1.81 | 1.16 | 0.178 | 0.66 |
TFPI
| 2 | rs7594359 | 188117093 | Intronic | T | C | 0.461 | 0.441 | 0.52 | 1.08 | 0.472 | 0.93 |
TFPI
| 2 | rs2192824 | 188077036 | Intronic | T | C | 0.449 | 0.428 | 0.54 | 1.09 | 0.461 | 0.93 |
TFPI
| 2 | rs13424790 | 188032097 | Downstream | G | T | 0.317 | 0.310 | 0.08 | 1.03 | 0.778 | 0.93 |
TFPI
| 2 | rs8176548 | 188048580 | Intronic | T | C | 0.351 | 0.347 | 0.02 | 1.02 | 0.878 | 0.93 |
TFPI
| 2 | rs10187622 | 188122406 | Intronic | T | C | 0.161 | 0.165 | 0.03 | 0.97 | 0.864 | 0.93 |
TFPI
| 2 | rs12613071 | 188096556 | Intronic | C | T | 0.202 | 0.195 | 0.09 | 1.04 | 0.762 | 0.93 |
Conditional- and haplotype analysis of the F5SNPs associated with breast cancer
SNP | Original ORs (P-values) | ORs (P-values) conditioned on rs12120605 | ORs (P-values) conditioned on rs6427202 | ORs (P-values) conditioned on rs9332542 | ORs (P-values) conditioned on rs6427199 |
---|---|---|---|---|---|
rs12120605
| 1.49 (0.024) | - |
1.55 (0.015)
|
1.54 (0.016)
|
1.62 (0.009)
|
rs6427202
| 1.32 (0.021) |
1.36 (0.010)
| - | 1.19 (0.218) | 1.24 (0.085) |
rs9332542
| 1.32 (0.022) |
1.35 (0.014)
| 1.20 (0.244) | - | 1.23 (0.095) |
rs6427199
| 1.27 (0.036) |
1.33 (0.014)
| 1.22 (0.111) | 1.20 (0.141) | - |
Relation between hemostatic parameters and breast cancer
Hemostatic parameter | Cases (n) | Controls (n) | OR | 95% CI |
P-value |
---|---|---|---|---|---|
Coagulation activity:
| |||||
ETP (%)*
| |||||
<90th percentile | 309 | 246 | Ref. | Ref. | Ref. |
>90th percentile | 37 | 27 | 1.09 | 0.65-1.84 | 0.744 |
Lag time (%)*
| |||||
>10th percentile | 211 | 246 | Ref. | Ref. | Ref. |
<10th percentile | 135 | 27 | 5.83 | 3.71-9.16 | <0.001 |
ttPeak (%)*
| |||||
>10th percentile | 206 | 249 | Ref. | Ref. | Ref. |
<10th percentile | 140 | 24 | 7.05 | 4.40-11.29 | <0.001 |
Peak (%)*
| |||||
<90th percentile | 208 | 246 | Ref. | Ref. | Ref. |
>90thpercentile | 138 | 27 | 6.05 | 3.85-9.50 | <0.001 |
APC resistance (nAPC-sr)
| |||||
FV Leiden non-carriers
| |||||
<90th percentile | 190 | 228 | Ref. | Ref. | Ref. |
>90th percentile | 135 | 25 | 6.48 | 4.06-10.35 | <0.001 |
FV Leiden carriers
| |||||
<90th percentile | 4 | 18 | Ref. | Ref. | Ref. |
>90th percentile | 17 | 2 | 38.3 | 6.2-236.6 | <0.001 |
D-dimer (ng/mL)
| |||||
<90th percentile | 292 | 246 | Ref. | Ref. | Ref. |
>90th percentile | 65 | 27 | 2.03 | 1.26-3.28 | 0.004 |
Coagulation inhibitors:
| |||||
AT (%)
| |||||
>10th percentile | 215 | 246 | Ref. | Ref. | Ref. |
<10th percentile | 135 | 27 | 5.72 | 3.64-8.99 | <0.001 |
Protein C (%)
| |||||
>10th percentile | 310 | 246 | Ref. | Ref. | Ref. |
<10th percentile | 40 | 27 | 1.18 | 0.702-1.97 | 0.539 |
Protein S (%)
| |||||
>10th percentile | 325 | 246 | Ref. | Ref. | Ref. |
<10th percentile | 22 | 27 | 0.62 | 0.34-1.11 | 0.106 |
Free TFPI (ng/mL)
| |||||
>10th percentile | 319 | 246 | Ref. | Ref. | Ref. |
<10th percentile | 39 | 27 | 1.11 | 0.66-1.87 | 0.683 |