1 Introduction
2 Material and Methods
2.1 Patients and Controls
Characteristic | Patients (n = 258) | Controls (n = 282) |
---|---|---|
Mean age (years) ± SD | 58.4 ± 9.7 | 57.4 ± 7.5 |
Histological grade | ||
G1 | 83 (32.2 %) | |
G2 | 85 (32.9 %) | |
G3 | 90 (34.9 %) | |
Gx | 0 (0.0 %) | |
Clinical stage | ||
I | 96 (37.2 %) | |
II | 40 (15.5 %) | |
III | 88 (34.1 %) | |
IV | 34 (13.2 %) | |
Histological type | ||
Serous | 90 (34.9 %) | |
Mucinous | 30 (11.6 %) | |
Endometrioid | 48 (18.6 %) | |
Clear cell | 24 (9.3 %) | |
Brenne | 0 (0.0 %) | |
Mixed | 22 (8.5 %) | |
Solid | 18 (7.0 %) | |
Untyped carcinoma | 26 (10.1 %) |
2.2 Genotyping
2.3 Statistical Analysis
3 Results
3.1 BRCA/BRCA2 Mutation Analysis
3.2 Association of CTNNB1, APC, and AXIN2 Single Nucleotide Polymorphisms with Ovarian Cancer Development in Patients Without BRCA1/BRCA2 Mutations
Gene | rs no. | Allelesa
| MAFb
| Genotypes casesc
| Genotypes controlsc
|
p
genotypic value |
p
trend value |
p
allelic value | ORdominant (95 % CI)d; p value | ORrecessive (95 % CI)e; p value |
---|---|---|---|---|---|---|---|---|---|---|
CTNNB1
| rs4533622 | a/C | 0.46 | 78/113/37 | 90/122/70 | 0.057 | 0.092 | 0.082 | 0.901 (0.622–1.306); 0.583 | 0.587 (0.376–0.915); 0.018 |
CTNNB1
| rs2953 | g/T | 0.46 | 78/113/37 | 90/122/70 | 0.057 | 0.092 | 0.082 | 0.901 (0.622–1.306); 0.583 | 0.587 (0.376–0.915); 0.018 |
APC
| rs11954856 | g/T | 0.48 | 35/129/63 | 76/141/64 | 0.007 | 0.007 | 0.009 |
2.034 (1.302–3.178); 0.002
| 1.302 (0.871–1.948); 0.198 |
APC
| rs351771 | c/T | 0.45 | 88/114/26 | 86/139/57 | 0.015 |
0.006
|
0.006
| 0.698 (0.483–1.009); 0.055 | 0.508 (0.308–0.839); 0.007 |
APC
| rs459552 | a/T | 0.30 | 129/86/13 | 142/108/32 | 0.064 | 0.041 | 0.034 | 0.778 (0.548–1.106); 0.161 | 0.472 (0.242–0.923); 0.025 |
AXIN2
| rs4074947 | C/t | 0.19 | 137/80/10 | 182/89/10 | 0.577 | 0.298 | 0.302 | 1.208 (0.841–1.734); 0.306 | 1.249 (0.510–3.056); 0.626 |
AXIN2
| rs7224837 | A/g | 0.15 | 161/61/6 | 203/71/8 | 0.917 | 0.801 | 0.799 | 1.069 (0.727–1.573); 0.733 | 0.926 (0.316–2.708); 0.888 |
AXIN2
| rs3923087 | a/G | 0.22 | 133/84/10 | 171/97/14 | 0.814 | 0.775 | 0.777 | 1.089 (0.763–1.555); 0.640 | 0.882 (0.384–2.026); 0.767 |
AXIN2
| rs2240308 | A/g | 0.49 | 67/115/46 | 71/146/65 | 0.510 | 0.254 | 0.260 | 0.809 (0.546–1.197); 0.288 | 0.844 (0.551–1.292); 0.434 |
3.3 Association of CTNNB1, APC, and AXIN2 Haplotypes with Ovarian Cancer Development in Patients Without BRCA1/BRCA2 Mutations
Polymorphisms | χ2
| Global p value |
---|---|---|
CTNNB1
a
| ||
rs4533622_rs2953 | 3.038 | 0.386 |
APC
b
| ||
rs11954856_rs351771 | 9.352 | 0.025 |
rs351771_rs459552 | 6.945 | 0.074 |
rs11954856_rs351771_rs459552 | 11.141 | 0.133 |
AXIN2
c
| ||
rs4074947_rs7224837 | 1.702 | 0.636 |
rs7224837_rs3923087 | 0.245 | 0.970 |
rs3923087_rs2240308 | 2.976 | 0.395 |
rs4074947_rs7224837_rs3923087 | 1.739 | 0.973 |
rs7224837_rs3923087_rs2240308 | 4.037 | 0.775 |
rs4074947_rs7224837_rs3923087_rs2240308 | 7.383 | 0.946 |
3.4 Multifactor Dimensionality Reduction Analysis of Gene–Gene Interactions Among the Studied CTNNB1, APC, and AXIN2 Polymorphisms
Polymorphisms | Testing balanced accuracy | Cross validation consistency (%) |
p valuea
|
---|---|---|---|
CTNNB1_rs4533622, APC_rs11954856 | 0.5418 | 60 | 0.356 |
CTNNB1_rs4533622, APC_rs351771, AXIN2_rs4074947 | 0.5041 | 50 | 0.828 |
CTNNB1_rs4533622, APC_rs11954856, AXIN2_rs7224837, AXIN2_rs2240308 | 0.5719 | 100 | 0.068 |