Introduction
Material and Methods
Patients and Controls
Characteristic | Patients | Controls |
---|---|---|
(n = 273) | (n = 464) | |
Mean age ± SD | 53.9 ± 9.1 | 52.8 ± 8.2 |
Histological grade | ||
G1 | 81 (29.7 %) | |
G2 | 101 (37.0 %) | |
G3 | 91 (33.3 %) | |
Gx | 0 (0.0 %) | |
Clinical stage | ||
I | 104 (38.1 %) | |
II | 43 (15.8 %) | |
III | 91 (33.3 %) | |
IV | 35 (12.8 %) | |
Histological type | ||
Serous | 97 (35.5 %) | |
Mucinous | 30 (11.0 %) | |
Endometrioid | 53 (19.4 %) | |
Clear cell | 26 (9.5 %) | |
Brenne | 0 (0.0 %) | |
Mixed | 24 (8.8 %) | |
Solid | 18 (6.6 %) | |
Untyped carcinoma | 25 (9.2 %) |
Genotyping
Statistical Analysis
Results
Contribution of rs2072590 (HOXD-AS1), rs2665390 (TIPARP), rs10088218 and rs10098821 (8q24), rs3814113 (9p22), rs9303542 (SKAP1) and rs2363956 (ANKLE1) SNPs to Ovarian Cancer Development
Chr | rs no. | Allelesa
| MAFb
| Genotypes casesc
| Genotypes controlsc
| pgenotypic value | ptrend value | pallelic value | ORdominant (95 % CI)d; p value | ORrecessive(95 % CI)e; p value | |
---|---|---|---|---|---|---|---|---|---|---|---|
2q31
|
rs2072590
|
G / t
|
0.35
|
All
|
116 / 115 / 41
|
198 / 207 / 59
| 0.633 | 0.652 | 0.686 | 1.001 (0.740–1.355); 0.995 | 1.218 (0.793–1.873); 0.368 |
Serous | 38 / 43 / 16 | 0.579 | 0.343 | 0.379 | 1.156 (0.739–1.808); 0.526 | 1.356 (0.743–2.475); 0.320 | |||||
Mucinous | 11 / 16 / 3 | 0.644 | 0.797 | 0.905 | 1.286 (0.598–2.764); 0.519 | 0.763 (0.224–2.594); 1.000f
| |||||
Endometrioid | 28 / 15 / 10 | 0.067 | 0.690 | 0.762 | 0.665 (0.376–1.175) ; 0.159 | 1.596 (0.761–3.348); 0.212 | |||||
Clear cell | 9 / 11 / 6 | 0.301 | 0.183 | 0.230 | 1.406 (0.614–3.221); 0.418 | 2.059 (0.794–5.338); 0.130 | |||||
Mixed | 11 / 10 / 3 | 0.952 | 0.813 | 0.933 | 0.880 (0.386–2.005); 0.760 | 0.981 (0.284–3.390); 1.000f
| |||||
Solid tumor | 7 / 9 / 1 | 0.645 | 0.750 | 0.891 | 1.063 (0.398–2.843); 0.903 | 0.429 (0.056–3.297); 0.708f
| |||||
Untyped | 12 / 11 / 2 | 0.748 | 0.471 | 0.566 | 0.806 (0.360–1.806); 0.600 | 0.597 (0.137–2.598); 0.756f
| |||||
3q25
|
rs2665390
|
c / T
|
0.09
|
All
|
218 / 50 / 2
|
380 / 77 / 5
| 0.744 | 0.715 | 0.784 | 1.105 (0.742–1.625); 0.610 | 0.682 (0.131–3.542); 1.000f
|
Serous | 75 / 20 / 1 | 0.619 | 0.389 | 0.463 | 1.298 (0.756–2.226); 0.343 | 0.962 (0.111–8.333); 1.000f
| |||||
Mucinous | 27 / 3 / 0 | 0.522 | 0.255 | 0.354f
| 0.515 (0.153–1.739); 0.452f
| N/A | |||||
Endometrioid | 43 / 8 / 0 | 0.740 | 0.606 | 0.734 | 0.862 (0.391–1.903); 0.713 | N/A | |||||
Clear cell | 20 / 5 / 1 | 0.425 | 0.344 | 0.471 | 1.390 (0.541–3.571); 0.492 | 3.656 (0.411–32.504); 0.281f
| |||||
Mixed | 17 / 7 / 0 | 0.261 | 0.240 | 0.082 | 1.908 (0.766–4.751); 0.159 | N/A | |||||
Solid tumor | 15 / 3 / 0 | 0.906 | 0.829 | 0.400f
| 0.818 (0.234–2.856); 1.000f
| N/A | |||||
Untyped | 21 / 4 / 0 | 0.867 | 0.740 | 0.791 | 0.883 (0.295–2.641); 1.000f
| N/A | |||||
8q24
|
rs10088218
|
a / G
|
0.12
|
All
|
223 / 44 / 4
|
357 / 100 / 7
| 0.214 | 0.120 | 0.137 | 0.718 (0.491–1.050); 0.086 | 0.978 (0.284–3.373); 1.000f
|
Serous | 80 / 16 / 0 | 0.249 | 0.118 | 0.152 | 0.667 (0.374–1.190); 0.168 | N/A | |||||
Mucinous | 26 / 4 / 0 | 0.427 | 0.193 | 0.301f
| 0.513 (0.175–1.504); 0.265f
| N/A | |||||
Endometrioid | 42 / 11 / 0 | 0.655 | 0.566 | 0.679 | 0.874 (0.435–1.757); 0.705 | N/A | |||||
Clear cell | 21 / 4 / 1 | 0.519 | 0.874 | 0.873 | 0.794 (0.293–2.158); 0.812f
| 2.611 (0.309–22.066); 0.356f
| |||||
Mixed | 19 / 3 / 2 | 0.036 | 0.642 | 0.805 | 0.878 (0.320–2.408); 1.000f
| 5.935 (1.164–30.263); 0.068f
| |||||
Solid tumor | 15 / 2 / 0 | 0.531 | 0.260 | 0.418f
| 0.445 (0.100–1.977); 0.383f
| N/A | |||||
Untyped | 20 / 4 / 1 | 0.529 | 0.953 | 0.952 | 0.834 (0.306–2.276); 1.000f
| 2.720 (0.321–23.020); 0.345 | |||||
8q24
|
rs10098821
|
C / t
|
0.11
|
All
|
233 / 34 / 3
|
363 / 94 / 6
| 0.028 |
0.014
| 0.016 | 0.576 (0.382–0.870); 0.008 | 0.856 (0.212–3.451); 1.000f
|
Serous | 84 / 12 / 0 | 0.099 |
0.033
| 0.045 | 0.519 (0.272–0.988); 0.043 | N/A | |||||
Mucinous | 25 / 4 / 0 | 0.558 | 0.285 | 0.390f
| 0.581 (0.196–1.708); 0.481f
| N/A | |||||
Endometrioid | 44 / 9 / 0 | 0.583 | 0.358 | 0.451 | 0.743 (0.351–1.576); 0.435f
| N/A | |||||
Clear cell | 25 / 1 / 0 | 0.093 | 0.033 | 0.036f
| 0.145 (0.019–1.085); 0.025f
| N/A | |||||
Mixed | 19 / 3 / 2 | 0.023 | 0.514 | 0.667 | 0.955 (0.348–2.623); 1.000f
| 6.924 (1.321–36.304); 0.054f
| |||||
Solid tumor | 16 / 1 / 0 | 0.293 | 0.122 | 0.165f
| 0.227 (0.030–1.732); 0.141f
| NA | |||||
Untyped | 20 / 4 / 1 | 0.488 | 0.905 | 0.905 | 0.908 (0.332–2.479); 1.000f
| 3.174 (0.367–27.435); 0.310f
| |||||
9p22
|
rs3814113
|
c / T
|
0.41
|
All
|
123 / 114 / 35
|
167 / 213 / 82
| 0.033 |
0.010
| 0.009 | 0.696 (0.505–0.930); 0.015 | 0.684 (0.446–1.050); 0.081 |
Serous | 50 / 36 / 11 | 0.016 |
0.006
| 0.006 |
0.532 (0.342–0.827); 0.005
| 0.593 (0.303–1.160); 0.123 | |||||
Mucinous | 12 / 12 / 6 | 0.809 | 0.905 | 0.903 | 0.849 (0.399–1.806); 0.671 | 1.159 (0.459–2.925); 0.755 | |||||
Endometrioid | 19 / 24 / 9 | 0.996 | 0.936 | 0.935 | 0.983 (0.542–1.784); 0.956 | 0.970 (0.455–2.068); 0.937 | |||||
Clear cell | 12 / 11 / 3 | 0.524 | 0.257 | 0.310 | 0.661 (0.299–1.461); 0.303 | 0.605 (0.177–2/062); 0.596f
| |||||
Mixed | 9 / 12 / 3 | 0.800 | 0.656 | 0.762 | 0.944 (0.404–2.203); 0.893 | 0.662 (0.193–2.272); 0.782f
| |||||
Solid tumor | 10 / 7 / 1 | 0.178 | 0.064 | 0.085 | 0.453 (0.175–1.170); 0.094 | 0.273 (0.036–2.078); 0.335f
| |||||
Untyped | 11 / 12 / 2 | 0.422 | 0.226 | 0.277 | 0.721 (0.320–1.623); 0.427 | 0.403 (0.093–1.744); 0.282f
| |||||
17q21
|
rs9303542
|
A / g
|
0.25
|
All
|
134 / 123 / 15
|
261 / 175 / 28
| 0.134 | 0.162 | 0.193 | 1.324 (0.981–1.788); 0.067 | 0.909 (0.476–1.734); 0.772 |
Serous | 54 / 36 / 6 | 0.997 | 0.975 | 0.975 | 1.000 (0.642–1.558); 1.000 | 1.038 (0.418–2.581); 0.936 | |||||
Mucinous | 17 / 12 / 1 | 0.823 | 0.785 | 0.907 | 0.983 (0.467–2.072); 0.964 | 0.537 (0.071–4.089); 1.000f
| |||||
Endometrioid | 24 / 26 / 3 | 0.270 | 0.230 | 0.285 | 1.554 (0.876–2.751); 0.128 | 0.934 (0.274–3.185); 1.000f
| |||||
Clear cell | 12 / 11 / 3 | 0.414 | 0.207 | 0.274 | 1.500 (0.679–3.314); 0.313 | 2.031 (0.575–7.179); 0.222f
| |||||
Mixed | 9 / 15 / 0 | 0.039 | 0.315 | 0.413 | 2.143 (0.919–4.997); 0.072 | N/A | |||||
Solid tumor | 9 / 9 / 0 | 0.388 | 0.988 | 0.988 | 1.286 (0.501–3.299); 0.600 | N/A | |||||
Untyped | 9 / 14 / 2 | 0.138 | 0.076 | 0.112 | 2.286 (0.990–5.280); 0.047 | 1.354 (0.304–6.038); 0.660f
| |||||
19p13
|
rs2363956
|
G / t
|
0.49
|
All
|
56 / 154 / 62
|
115 / 244 / 105
| 0.196 | 0.399 | 0.451 | 1.271 (0.885–1.825); 0.193 | 1.009 (0.706–1.443); 0.959 |
Serous | 17 / 53 / 26 | 0.235 | 0.139 | 0.169 | 1.531 (0.870–2.694); 0.137 | 1.270 (0.770–2.094); 0.348 | |||||
Mucinous | 7 / 18 / 5 | 0.559 | 0.738 | 0.837 | 1.083 (0.453–2.590); 0.858 | 0.684 (0.255–1.831); 0.650f
| |||||
Endometrioid | 13 / 28 / 12 | 0.948 | 0.971 | 0.979 | 1.104 (0.524–1.962); 0.967 | 1.001 (0.507–1.974); 0.998 | |||||
Clear cell | 8 / 11 / 7 | 0.719 | 0.911 | 0.906 | 0.741 (0.314–1.751); 0.493 | 1.260 (0.515–3.079); 0.612 | |||||
Mixed | 6 / 17 / 1 | 0.059 | 0.203 | 0.265 | 0.989 (0.383–2.551); 0.981 | 0.149 (0.020–1.114); 0.039f
| |||||
Solid tumor | 1 / 12 / 5 | 0.145 | 0.146 | 0.206 | 5.602 (0.737–42.578); 0.088f
| 1.315 (0.458–3.774); 0.574f
| |||||
Untyped | 4 / 15 / 6 | 0.512 | 0.476 | 0.579 | 1.730 (0.582–5.146); 0.473f
| 1.080 (0.420–2.774); 0.873 |
MDR Analysis of Gene-gene Interactions among the rs2072590 (HOXD-AS1), rs2665390 (TIPARP), rs10088218 and rs10098821 (8q24), rs3814113 (9p22), rs9303542 (SKAP1) and rs2363956 (ANKLE1) SNPs
Polymorphisms | Testing balanced accuracy | Cross validation consistency | p valuea
|
---|---|---|---|
8q24_rs10098821, 9p22_rs3814113 | 0.516 | 60 % | 0.682 |
8q24_rs10098821, 9p22_rs3814113, 17q21_rs9303542 | 0.514 | 40 % | 0.708 |
2q31_rs2072590, 9p22_rs3814113, 17q12_rs757210, 19p13_rs2363956 | 0.507 | 70 % | 0.783 |