Background
Methods
Study population
Characteristics | Patients (%) |
---|---|
Total | 577 |
Age at diagnosis | |
≤40 | 133 (23.1) |
>40 | 444 (76.9) |
Menopausal status | |
Non menopausal | 298 (51.6) |
Menopausal | 279 (48.4) |
Tumor size | |
T1–T2 | 381 (66) |
T3–T4 | 167 (29) |
Unknown | 29 (5) |
Lymph node involvement | |
Negative | 230 (39.9) |
Positive | 328 (56.8) |
Unknown | 19 (3.3) |
Metastasis | |
Negative | 362 (62.7) |
Positive | 10 (1.7) |
Unknown | 205 (35.5) |
SBR grade | |
SBR 1–2 | 329 (57) |
SBR 3 | 192 (33.3) |
Unknown | 56 (9.7) |
Histology | |
Ductual | 513 (88.9) |
Lobular | 23 (4) |
Other | 25 (4.3) |
Unknown | 16 (2.8) |
Estrogen receptor | |
Negative | 195 (33.8) |
Positive | 255 (44.2) |
Unknown | 127 (22) |
Progesteron receptor | |
Negative | 240 (41.6) |
Positive | 210 (36.4) |
Unknown | 127 (22) |
Her-2 status | |
Negative | 75 (13) |
Positive | 39 (6.8) |
Unknown | 463 (80.2) |
Genomic DNA extraction and SNP genotyping analysis
SNPs | Primer sequences | Restriction enzymes | Fragments size (bp) |
---|---|---|---|
−347 G/GA rs5030625 −160 C/A rs16260 | Forword: 5′-GCCCCGACTTGTCTCTCTAC-3′ Reverse: 5′-GGCCACAGCCAATCAGCA-3′ |
BanII | G: 263 + 116 + 68 GA: 332 + 116 |
HphI | C: 181 + 177 + 89 A: 266 + 181 | ||
+54 C/T rs1801026 | Forword: 5′-CAGACAAAGACCAGGACTAT-3′ Reverse: 5′-AAGGGAGCTGAAAAACCACCAGCCAC-3′ |
PmlI | C: 146 + 26 T: 172 |
Statistical analysis
Results
CDH1 SNPs and their association with clinicopathological characteristics of breast cancer patients
Characteristics | −347 G/GA
| −160 C/A
| +54 C/T
| |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
GG
b
|
GGA + GAGA
|
P
|
OR (95% CI)
|
CC
b
|
CA + AA
|
P
|
OR (95% CI)
|
CC
b
|
CT + TT
|
P
|
OR (95% CI)
| |
Age at diagnosis | ||||||||||||
≤40 | 96 | 37 | 61 | 72 | 48 | 85 | ||||||
>40 | 322 | 122 | 0.93 | 0.98 (0.63–1.51) | 204 | 240 | 0.98 | 0.99 (0.67–1.47) | 157 | 287 | 0.87 | 1.03 (0.68–1.54) |
Menopausal status | ||||||||||||
Non menopausal | 225 | 73 | 145 | 153 | 107 | 191 | ||||||
Menopausal | 193 | 86 | 0.08 | 1.37 (0.95–1.98) | 120 | 159 | 0.17 | 1.25 (0.90–1.74) | 98 | 181 | 0.84 | 1.03 (0.73–1.45) |
Tumor size | ||||||||||||
T1–T2 | 279 | 102 | 166 | 215 | 134 | 247 | ||||||
T3–T4 | 119 | 48 | 0.63 | 1.1 (0.73–1.65) | 81 | 86 | 0.28 | 0.82 (0.56–1.18) | 61 | 106 | 0.76 | 0.94 (0.64–1.37) |
Lymph node involvement | ||||||||||||
Negative | 167 | 63 | 116 | 114 | 73 | 157 | ||||||
Positive | 239 | 89 | 0.94 | 0.98 (0.67–1.44) | 141 | 187 | 0.08 | 1.34 (0.96–1.80) | 127 | 201 | 0.09 | 0.73 (0.51–1.05) |
Metastasis | ||||||||||||
Negative | 264 | 98 | 166 | 196 | 121 | 241 | ||||||
Positive | 8 | 2 | 0.46a
| 0.67 (0.14–3.20) | 3 | 7 | 0.25a
| 1.97 (0.50–7.70) | 2 | 8 | 0.37a
| 2 (0.42–9.60) |
SBR grade | ||||||||||||
SBR 1–2 | 232 | 97 | 150 | 179 | 112 | 217 | ||||||
SBR 3 | 148 | 44 | 0.10 | 0.71 (0.47–1.07) | 91 | 101 | 0.69 | 0.93 (0.65–1.32) | 74 | 118 | 0.30 | 0.82 (0.56–1.19) |
Histology | ||||||||||||
Ductual | 376 | 137 | 240 | 273 | 183 | 330 | ||||||
Lobular | 18 | 5 | 0.59 | 0.76 (0.27–2.09) | 11 | 12 | 0.92 | 0.95 (0.41–2.21) | 6 | 17 | 0.35 | 1.57 (0.60–4.05) |
Haplotypes | Frequencies |
P
| |||
---|---|---|---|---|---|
−347G/GA
| −160C/A
| +54C/T
| Patients | Controls | |
G
|
C
|
C
| 0.323 | 0.405 | |
G
|
C
|
T
| 0.238 | 0.265 | 0.270 |
G
|
A
|
C
| 0.177 | 0.147 |
<10
−4
|
G
|
A
|
T
| 0.109 | 0.032 |
<10
−4
|
GA
|
C
|
C
| 0.068 | 0.101 | 0.380 |
GA
|
C
|
T
| 0.048 | 0.024 |
0.023
|
GA
|
A
|
C
| 0.022 | 0.021 | 0.660 |
GA
|
A
|
T
| 0.012 | 0.003 | 0.230 |
Characteristics |
GCC
a
|
GCT
|
GAC
|
GAT
|
GACC
|
GACT
|
GAAC and GAAT
|
---|---|---|---|---|---|---|---|
Age at diagnosis | |||||||
≤40 | 0.358 | 0.213 | 0.194 | 0.084 | 0.027 | 0.094 | 0.030 |
>40 | 0.312 | 0.248 | 0.173 | 0.117 | 0.081 | 0.032 | 0.036 |
P
|
0.15
|
0.83
|
0.15
|
0.015
|
0.01
|
0.21
| |
OR (CI 95%) | 1 | 1.38 (0.89–2.13) | 1.06 (0.64–1.74) | 1.54 (0.85–2.79) | 3.74 (1.29–10.82) | 0.37 (0.17–0.79) | 1.37 (0.82–2.28) |
Menopausal status | |||||||
Non menopausal | 0.354 | 0.236 | 0.172 | 0.105 | 0.056 | 0.049 | 0.028 |
Menopausal | 0.291 | 0.245 | 0.182 | 0.114 | 0.081 | 0.043 | 0.044 |
P
|
0.21
|
0.26
|
0.26
|
0.098
|
0.92
|
0.25
| |
OR (CI 95%) | 1 | 1.26 (0.88–1.81) | 1.29 (0.83–2.01) | 1.29 (0.83–2.01) | 1.69 (0.91–3.16) | 1.04 (0.51–2.11) | 1.73 (0.64–4.39) |
Tumor size | |||||||
T1–T2 | 0.318 | 0.237 | 0.192 | 0.105 | 0.057 | 0.051 | 0.038 |
T3–T4 | 0.326 | 0.242 | 0.149 | 0.124 | 0.085 | 0.038 | 0.035 |
P
|
0.91
|
0.23
|
0.6
|
0.33
|
0.46
|
0.76
| |
OR (CI 95%) | 1 | 0.98 (0.65–1.46) | 0.73 (0.44–1.21) | 1.13 (0.71–1.81) | 1.41 (0.71–2.79) | 0.74 (0.33–1.66) | 0.86 (0.32–2.27) |
Lymph node involvement | |||||||
Negative | 0.320 | 0.284 | 0.162 | 0.084 | 0.053 | 0.047 | 0.050 |
Positive | 0.323 | 0.208 | 0.195 | 0.123 | 0.080 | 0.047 | 0.023 |
P
|
0.19
|
0.34
|
0.24
|
0.29
|
0.91
|
0.19
| |
OR (CI 95%) | 1 | 0.78 (0.54–1.13) | 1.26 (0.78–2.04) | 1.34 (0.82–2.17) | 1.43 (0.74–2.77) | 0.96 (0.47–1.95) | 0.55 (0.22–1.81) |
SBR grade | |||||||
SBR 1–2 | 0.314 | 0.225 | 0.167 | 0.131 | 0.086 | 0.047 | 0.030 |
SBR 3 | 0.365 | 0.230 | 0.192 | 0.085 | 0.040 | 0.055 | 0.025 |
P
|
0.46
|
0.96
|
0.053
|
0.049
|
0.97
|
0.84
| |
OR (CI 95%) | 1 | 0.86 (0.57–1.29) | 0.99 (0.61–1.61) | 0.61 (0.37–1.00) | 0.44 (0.19–0.99) | 1.01 (0.50–2.05) | 0.91 (0.34–2.42) |
Histology | |||||||
Ductual | 0.291 | 0.231 | 0.139 | 0.157 | 0.122 | 0.026 | 0.032 |
Lobular | 0.329 | 0.245 | 0.179 | 0.103 | 0.060 | 0.050 | 0.033 |
P
|
0.74
|
0.83
|
0.2
|
0.11
|
0.52
|
0.72
| |
OR (CI 95%) | 1.00 | 1.12 (0.57–2.22) | 0.90 (0.35–2.34) | 1.59 (0.78–3.23) | 2.06 (0.86–4.94) | 0.62 (0.14–2.67) | 0.91 (0.54–1.52) |
CDH1 SNPs and clinicopathological characteristics associated with survival in patients with breast cancer
Characteristics | Disease-free survival | Overall survival | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Univariate analysis | Multivariate analysis | Univariate analysis | Multivariate analysis | |||||||||
HR | 95% CI |
P
| HR | 95% CI |
P
| HR | 95% CI |
P
| HR | 95% CI |
P
| |
Agea
| 0.74 | 0.51–1.08 | 0.121 | ni | 0.75 | 0.33–1.68 | 0.487 | ni | ||||
Menopausal statusb
| 0.92 | 0.66–1.28 | 0.638 | ni | 0.87 | 0.42–1.76 | 0.702 | ni | ||||
Tumor sizec
| 1.87 | 1.33–2.64 | 0.0003 | 1.80 | 1.27–2.56 | 0.001 | 1.44 | 0.69–3.02 | 0.326 | ni | ||
Lymph node involvementd
| 1.75 | 1.22–2.51 | 0.002 | 1.66 | 1.14–2.40 | 0.007 | 2.97 | 1.21–7.30 | 0.017 | 3.26 | 1.22–8.69 | 0.018 |
Metastasisd
| 3.03 | 1.47–6.22 | 0.003 | ni | 5.64 | 1.67–19.01 | 0.005 | ni | ||||
SBR gradee
| 1.09 | 0.77–1.56 | 0.599 | ni | 2.29 | 1.08–4.84 | 0.030 | 2.20 | 1.00–4.81 | 0.048 | ||
Histologyf
| 1.62 | 0.82–3.20 | 0.157 | ni | 0.80 | 0.11–5.92 | 0.833 | ni | ||||
Estrogen receptord
| 1.34 | 0.91–1.95 | 0.127 | ni | 0.73 | 0.33–1.60 | 0.435 | ni | ||||
Progesteron receptord
| 1.16 | 0.80–1.67 | 0.419 | ni | 0.88 | 0.40–1.95 | 0.763 | ni | ||||
Her-2 statusd
| 1.03 | 0.44–2.40 | 0.938 | ni | 0.67 | 0.06–7.44 | 0.746 | ni | ||||
CDH1 −347 G/GA
g
| 0.92 | 0.63–1.35 | 0.694 | ni | 0.09 | 0.01–0.68 | 0.020 | 0.12 | 0.01–0.89 | 0.039 | ||
CDH1 −160 C/A
g
| 0.92 | 0.66–1.28 | 0.650 | ni | 1.27 | 0.62–2.63 | 0.505 | ni | ||||
CDH1 +54 C/T
g
| 0.98 | 0.69–1.40 | 0.951 | ni | 0.52 | 0.26–1.06 | 0.075 | 0.40 | 0.18–0.87 | 0.022 |