http://dx.doi.org/10.4143/crt.2015.098 l http://www.e-crt.org l. 1. Nucleotide Excision Repair Gene ERCC2 and ERCC5 Variants Increase. Risk of Uterine Cervical ...
pISSN 1598-2998, eISSN 2005-9256 Cancer Res Treat. 2016;48(2):708-714
http://dx.doi.org/10.4143/crt.2015.098 Open Access
Original Article
Nucleotide Excision Repair Gene ERCC2 and ERCC5 Variants Increase Risk of Uterine Cervical Cancer
Jungnam Joo, PhD1, Kyong-Ah Yoon, PhD2, Tomonori Hayashi, PhD3, Sun-Young Kong, MD, PhD4, Hye-Jin Shin, MS5, Boram Park, MS1, Young Min Kim, PhD6, Sang-Hyun Hwang, MD, PhD7, Jeongseon Kim, PhD8, Aesun Shin, MD, PhD8,9, Joo-Young Kim, MD, PhD5,10 Biometric Research Branch, 2Lung Cancer Branch, National Cancer Center, Goyang, Korea, Department of Radiobiology and Molecular Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan, 4 Translational Epidemiology Research Branch and Department of Laboratory Medicine, 5 Radiation Medicine Branch, National Cancer Center, Goyang, Korea, 6 Department of Statistics, Radiation Effects Research Foundation, Hiroshima, Japan, 7 Hematologic Malignancy Branch and Department of Laboratory Medicine, 8Molecular Epidemiology Branch, National Cancer Center, Goyang, 9 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, 10 Center for Proton Therapy, Research Institute and Hospital, National Cancer Center, Goyang, Korea 1
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Supplementary Data
Table of Contents Supplementary Fig. S1 ........................................................................................................................................................................... 2 Supplementary Table 1 .......................................................................................................................................................................... 3 Supplementary Table 2 .......................................................................................................................................................................... 5 Supplementary Table 3 .......................................................................................................................................................................... 6
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Copyright ⓒ 2016 by the Korean Cancer Association This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Cancer Res Treat. 2016;48(2):708-714
–log10 (p)
3
2
1
rs3213245
rs25487
rs2139720
rs25489
rs1799782
rs1869258
rs560191
rs2602141
rs1042522
rs12951053
rs709816
rs7018118
rs6991811
rs1805800
rs1805844
rs1061302
rs1063045
rs1805794
rs9557946
rs17655
rs751402
rs2094258
rs9557929
rs1319052
rs3810366
rs11878644
rs238406
rs238417
rs454421
0
RS number
Supplementary Fig. S1. p-values from Hardy-Weinberg disequilibrium test. High p-value indicates no evident deviation from Hardy-Weinberg equilibrium (the horizontal line is the threshold of a=0.05/29=1.7×10-3 using the Bonferroni correction).
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CANCER RESEARCH AND TREATMENT
Jungnam Joo, ERCC2 and ERCC5 Variants Increase Cervical Cancer Risk
Supplementary Table 1. Crude and age-adjusted p-values of MIN2 for 29 SNPs determined using the Bonferroni correction Gene ERCC2
ERCC5
NBS1
SNP
RS number
Genotype
ERCC2-T1
rs454421
ERCC2-T2
rs238417
ERCC2-T5
rs238406
ERCC2-T8
rs3810366
ERCC2-T9
rs11878644
ERCC2-T14
rs1319052
ERCC5-T1
rs9557929
ERCC5-T4
rs2094258
ERCC5-T6
rs751402
ERCC5-T10
rs17655
ERCC5-T12
rs9557946
NBS1-185
rs1805794
NBS1-34
rs1063045
NBS1-672
rs1061302
NBS1-i-800
rs1805844
NBS1-U-500
rs1805800
G/G G/A A/A C/C C/G G/G C/C C/A A/A G/G C/G C/C T/T C/T C/C A/A A/G G/G G/G G/C C/C C/C C/T T/T G/G G/A A/A G/G C/G C/C A/A A/T T/T G/G G/C C/C C/C C/T T/T A/A A/G G/G A/A A/G G/G G/G G/A A/A
No.
Crude
Age adjusted
Case
Control
OR
p-value
OR
p-value
107 265 106 122 262 94 135 255 88 102 266 110 102 265 111 271 178 29 134 225 119 162 221 95 240 187 51 101 230 147 138 227 113 140 241 97 140 241 97 140 242 96 139 242 97 140 241 97
293 434 195 221 453 248 247 447 228 257 456 209 248 463 211 556 314 52 242 450 230 301 426 195 495 346 81 276 437 209 238 455 229 268 471 183 276 469 177 272 458 192 267 456 199 267 457 198
1 1.672 1.488 1 1.048 0.687 1 1.044 0.706 1 1.470 1.326 1 1.392 1.279 1 1.163 1.144 1 0.903 0.934 1 0.964 0.905 1 1.115 1.299 1 1.438 1.922 1 0.860 0.851 1 0.980 1.015 1 1.013 1.080 1 1.027 0.972 1 1.019 0.936 1 1.006 0.934
0.0013
1 1.712 1.619 1 1.013 0.644 1 1.013 0.680 1 1.516 1.413 1 1.438 1.350 1 1.145 1.044 1 0.908 0.948 1 0.973 0.895 1 1.065 1.196 1 1.508 2.013 1 0.898 0.876 1 1.045 1.040 1 1.058 1.104 1 1.056 0.973 1 1.008 0.971 1 0.993 0.960
0.0009
0.0171
0.0399
0.0345
0.0925
0.3258
0.7812
0.6708
0.2122
0.0001
0.3955
0.9892
0.7865
0.9617
0.8430
0.8271
0.0104
0.0391
0.0238
0.0647
0.5327
0.8482
0.6532
0.4848
< 0.0001
0.5340
0.9000
0.6829
0.9312
0.9525
0.9142
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Cancer Res Treat. 2016;48(2):708-714
Supplementary Table 1. Continued Gene
TP53
TP53BP1
XRCC1
SNP
RS number
Genotype
NBS1-U2200
rs6991811
NBS1-U3500
rs7018118
NBS1-399
rs709816
TP53-11
rs12951053
TP53-72
rs1042522
TP53BP1-1136
rs2602141
TP53BP1-353
rs560191
TP53BP1-U-1k
rs1869258
XRCC1-194
rs1799782
XRCC1-280
rs25489
XRCC1-399
rs25487
G/G G/T T/T T/T T/C C/C C/C C/T T/T T/T T/G G/G G/G C/G C/C T/T T/G G/G C/C G/C G/G A/A A/C C/C C/C C/T T/T G/G G/A A/A G/G A/G A/A C/C C/T T/T T/T T/C C/C
XRCC1-i10-141 rs2139720
XRCC1-77
rs3213245
No.
Crude
Age adjusted
Case
Control
OR
p-value
OR
p-value
139 242 97 139 242 97 202 216 60 248 190 40 190 216 72 116 255 107 114 256 108 112 256 110 219 211 48 371 100 7 257 194 27 411 64 3 401 74 3
265 480 177 274 473 175 398 403 121 509 361 52 383 438 101 268 457 197 235 490 197 236 485 201 414 406 102 717 195 10 500 354 68 758 156 8 754 161 7
1 0.961 1.045 1 1.009 1.093 1 1.056 0.977 1 1.080 1.579 1 0.994 1.437 1 1.289 1.255 1 1.077 1.130 1 1.112 1.153 1 0.982 0.890 1 0.991 1.353 1 1.066 0.773 1 0.757 0.692 1 0.864 0.806
0.9335
1 1.013 1.120 1 1.016 1.053 1 1.035 0.964 1 1.141 1.662 1 0.993 1.509 1 1.264 1.248 1 1.084 1.145 1 1.057 1.141 1 1.012 0.916 1 0.982 1.558 1 1.056 0.795 1 0.819 0.673 1 0.905 0.833
0.6717
0.7502
0.9441
0.1206
0.1263
0.2001
0.5864
0.5030
0.7387
0.9207
0.5352
0.1096
0.4352
0.8782
0.9741
0.0559
0.0854
0.2333
0.5513
0.5699
0.8924
0.8092
0.6618
0.2674
0.6355
ERCC, excision repair cross-complementing; XRCC, X-ray repair cross-complementing; SNP, single nucleotide polymorphism; OR, odds ratio.
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CANCER RESEARCH AND TREATMENT
Jungnam Joo, ERCC2 and ERCC5 Variants Increase Cervical Cancer Risk
Supplementary Table 2. Subgroup analyses of rs454421 and rs17655 Subgroup Age (yr) ≤ 40
RS number
Genotype
rs454421
rs17655
> 40
rs454421
rs17655
Histology Squamous cell carcinoma
rs454421
rs17655
Adenocarcinomas
rs454421
rs17655
HPV 18 type Yes
rs454421
rs17655
No
rs454421
rs17655
No.
Additive
Dominant
Recessive
Case
Control
OR
p-value
OR
p-value
OR
p-value
G/G G/A A/A G/G C/G C/C G/G G/A A/A G/G C/G C/C
16 47 17 17 37 26 91 218 89 84 193 121
293 434 195 276 437 209 293 434 195 276 437 209
1 1.260 1.589 1 1.425 2.032 1 1.224 1.499 1 1.376 1.894
0.1538
1 1.863 1.863 1 1.583 1.583 1 1.571 1.571 1 1.597 1.597
0.0287
1 1 1.006 1 1 1.643 1 1 1.074 1 1 1.490
0.9832
G/G G/A A/A G/G C/G C/C G/G G/A A/A G/G C/G C/C
89 224 89 88 191 123 16 32 13 11 31 19
293 434 195 276 437 209 293 434 195 276 437 209
1 1.238 1.534 1 1.358 1.845 1 1.117 1.247 1 1.481 2.194
G/G G/A A/A G/G C/G C/C G/G G/A A/A G/G C/G C/C
11 22 11 6 23 15 77 182 70 75 152 102
293 434 195 276 437 209 293 434 195 276 437 209
1 1.226 1.504 1 1.714 2.936 1 1.185 1.404 1 1.342 1.802
0.0281
0.0170
0.0001
0.0117
0.0002
0.5474
0.0326
0.3384
0.0127
0.0613
0.0009
1 1.638 1.638 1 1.524 1.524 1 1.310 1.310 1 1.942 1.942 1 1.397 1.397 1 2.705 2.705 1 1.524 1.524 1 1.447 1.447
0.1014
0.0011
0.0009
0.0004
0.0026
0.3659
0.0477
0.3442
0.0202
0.0043
0.0134
1 1 1.060 1 1 1.504 1 1 1.010 1 1 1.543 1 1 1.243 1 1 1.765 1 1 1.008 1 1 1.533
0.0465
0.6228
0.0029
0.6867
0.0022
0.9761
0.1286
0.5424
0.0794
0.9614
0.0027
Subgroup analyses were performed according to age (≤ 40, > 40), histology (squamous, adeno carcinomas), and HPV 18 type (HPV 18 type, others). OR, odds ratio; HPV, human papillomavirus.
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Supplementary Table 3. Proportional odds model for rs454421 in ERCC2 and rs17655 in ERCC5 according to age (≤ 40, > 40, control for 1, 2, 3), histology (adenocarcinoma, squamous cell carcinoma, control for 1, 2, 3), and HPV 18 type (HPV 18 type, others, control for 1,2,3) Subgroup Age
RS number
Genotype
rs454421
G/G G/A A/A G/G C/G C/C G/G G/A A/A G/G C/G C/C G/G G/A A/A G/G C/G C/C
rs17655
Histology
rs454421
rs17655
HPV18 type
rs454421
rs17655
No.
Additive
Dominant
1
2
3
OR
p-value
OR
p-value
OR
p-value
16 47 17 17 37 26 16 32 13 11 31 19 11 22 11 6 23 15
91 218 89 84 193 121 89 224 89 88 191 123 77 182 70 75 152 102
293 434 195 276 437 209 293 434 195 276 437 209 293 434 195 276 437 209
1 1.231 1.514 1 1.378 1.898 1 1.212 1.469 1 1.372 1.882 1 1.191 1.419 1 1.388 1.927
0.0087
1 1.616 1.616 1 1.581 1.581 1 1.561 1.561 1 1.577 1.577 1 1.498 1.498 1 1.563 1.563
0.0002
1 1 1.056 1 1 1.508 1 1 1.050 1 1 1.497 1 1 1.044 1 1 1.560
0.6866
< 0.0001
0.0167
< 0.0001
0.0430
0.0001
ERCC, excision repair cross-complementing; HPV, human papillomavirus; OR, odds ratio.
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CANCER RESEARCH AND TREATMENT
Recessive
0.0005
0.0007
0.0006
0.0039
0.0018
0.0009
0.7241
0.0013
0.7749
0.0010
