<p>Supplemental Tables:</p><p>CASP7 variants modify susceptibility to cervical cancer in Chinese women</p><p>Ting-Yan Shi 1,2, Jing He 2,3, Meng-Yun Wang 2, Mei-Ling Zhu 2, Ke-Da Yu 4, Zhi-Ming Shao </p><p>4, Meng-Hong Sun 5, Xiaohua Wu 6, Xi Cheng 6,*, Qingyi Wei 2,7,*</p><p>1 Department of Obstetrics and Gynecology, Zhongshan Hospital Fudan University, Shanghai</p><p>200032, China</p><p>2 Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 200032, China</p><p>3 State Key Laboratory of Oncology in South China, Department of Experimental Research, </p><p>Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center,</p><p>Guangzhou, Guangdong 510060, China</p><p>4 Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai </p><p>200032, China</p><p>5 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, </p><p>China</p><p>6 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, </p><p>Shanghai 200032, China</p><p>7 Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA</p><p>*Correspondence to：Xi Cheng, MD, PhD, Professor of Gynecologic Oncology, </p><p>Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center; 270 Dongan Road, Shanghai 200032, China. Tel: (+86-21) 64175590; Fax: (+86-21) 64174774; </p><p>E-mail: [email protected], or Qingyi Wei, MD, PhD, Cancer Institute, Fudan </p><p>University Shanghai Cancer Center, Shanghai, China. Tel: (+86-21) 64175590-5315, Fax: </p><p>(+86-21) 64172585; E-mail: [email protected] or Duke Cancer Institute, Duke </p><p>University Medical Center, Durham, NC 27710, USA; E-mail: [email protected]. Supplementary Table S1. Distributions of selected variables in cervical cancer cases and cancer-free controls</p><p>Variables Cases N (%) Controls N (%) Pa</p><p>All subjects 1,486 (100) 1,301 (100) Age, yr (Mean±SD) 45.9 ± 9.8 46.6 ± 8.8 0.126 < 46 (mean) 757 (50.9) 625 (48.0) ≥ 46 (mean) 729 (49.1) 676 (52.0) Age of primiparity, yr 23.5 ± 2.9 24.4 ± 2.4 <.0001 (Mean±SD) ≤ 24 (mean) 887 (63.4) 665 (51.8) > 24 (mean) 512 (36.6) 618 (48.2) Missing 87 18 Menopausal status <.0001 Premenopausal 1,067 (72.4) 756 (58.2) Postmenopausal 407 (27.6) 543 (41.8) Missing 12 2 BMIb, kg/m2 <.0001 < 25 1,140 (78.1) 847 (65.2) ≥ 25 319 (21.9) 453 (34.9) Missing 27 1 Histology b CIN-III 160 (10.8) SCC 1,164 (78.6) Adenocarcinoma 102 (6.9) Adenosquamous 37 (2.5) Others 18 (1.2) Missing 5 FIGO stage I 691 (55.6) II 503 (40.5) III 44 (3.5) IV 4 (0.3) Missing 244 Tumor size, cm < 4 908 (66.8) ≥ 4 451 (33.2) Missing 127 Pelvic LN Negative 1,091 (77.4) Positive 318 (22.6) Missing 77 LVSI Negative 839 (67.0) Positive 413 (33.0) Missing 234 Depth of cervical stromal invasion ≤ 1/2 665 (47.9) > 1/2 723 (52.1) Missing 98 ER expression Negative 745 (92.1) Positive 64 (7.9) Missing 677 PR expression Negative 783 (96.8) Positive 26 (3.2) Missing 677 FIGO, International Federation of Gynecology and Obstetrics; CIN, cervical intraepithelial neoplasia; SCC, squamous cell carcinoma; LN, Lymph Node; LVSI, lymph-vascular space invasion. a Two-sided 2 test for distributions between cases and controls; b According to the current WHO recommendations. Supplementary Table S2. Haplotype analysis for genotypes of CASP7 and cervical cancer risk Haplotypes Cases Controls Crude OR P Adjusted ORa Pa (N =2,972) (N =2,602) (95% CI) (95% CI) N % N % </p><p>Crs4353229 Grs12247479 1,173 39.5 1,094 42.0 1.00 1.00 </p><p>T10787498 G1127687</p><p>Crs4353229 Ars12247479 0 0.0 3 0.1 2.11 (0.41- 0.375 2.09 (0.40- 0.383</p><p>T10787498 G1127687 10.95) 11.00)</p><p>Crs4353229 Grs12247479 5 0.2 2 0.1 0.28 (0.06- 0.122 0.36 (0.07- 0.216</p><p>G10787498 G1127687 1.40) 1.83)</p><p>Crs4353229 Grs12247479 2 0.1 6 0.2 0.90 (0.76- 0.26 0.93 (0.77- 0.425</p><p>T10787498 A1127687 1.08) 1.12)</p><p>Trs4353229 Ars12247479 351 11.8 293 11.3 —— 0.962 —— 0.951</p><p>G10787498 G1127687</p><p>Trs4353229 Grs12247479 0 0.0 3 0.1 1.06 (0.84- 0.609 1.06 (0.83- 0.603</p><p>G10787498 A1127687 1.35) 1.37)</p><p>Trs4353229 Grs12247479 265 8.9 210 8.1 1.01 (0.82- 0.944 1.02 (0.82- 0.879</p><p>G10787498 G1127687 1.23) 1.26)</p><p>Trs4353229 Grs12247479 660 22.2 559 21.5 —— —— —— ——</p><p>T10787498 A1127687</p><p>Trs4353229 Grs12247479 516 17.4 432 16.6 —— —— —— ——</p><p>T10787498 G1127687 CI, confidence interval; OR, odds ratio a Obtained in logistic regression models with adjustment for age, age at primiparity, menopausal status, BMI The results were in bold, if P < 0.05 Supplementary Table S3. Stratification analysis for associations between CASP7 genotypes and cervical cancer risk in Eastern Chinese women</p><p>Variable rs4353229 Adjusted Pa Pho rs12247479 Adjusted Pa Ph rs10787498 Adjusted Pa Ph rs1127687 Adjusted Pa Ph</p><p> s (cases/contr ORa (95% m (cases/contr ORa (95% om (cases/contr ORa (95% om (cases/contr ORa (95% om</p><p> ols) CI) ols) CI) ols) CI) ols) CI)</p><p>CC/ TT GG AG/A TT GT/G GG AG/A</p><p>CT A G A</p><p>Age, yr</p><p>≤ 46 478/ 279/ 1.09 (0.87- 0. 0.43 572/4 185/1 1.14 (0.86- 0.41 0. 456/4 301/2 1.22 (0.97- 0.09 0. 477/3 280/2 0.93 (0.74- 0.55 0.</p><p>(mean) 411 214 1.38) 46 7 87 38 1.45) 7 39 04 21 1.53) 2 55 92 33 1.17) 4 60</p><p>0 3 8 7 </p><p>>46 466/ 263/ 1.26 (0.99- 0. 581/5 148/1 1.00 (0.76- 0.99 473/4 256/2 1.10 (0.87- 0.44 419/4 310/2 1.22 (0.97- 0.08</p><p>(mean) 468 208 1.60) 06 36 40 1.32) 9 53 23 1.39) 2 12 64 1.54) 7 </p><p>2 </p><p>Age at primiparity, yr</p><p>≤ 24 564/ 328/ 1.18 (0.95- 0. 0.82 690/5 197/1 0.94 (0.74- 0.61 0. 562/4 325/2 0.98 (0.80- 0.87 0. 523/4 364/2 1.19 (0.96- 0.11 0.</p><p>(mean) 447 218 1.46) 14 5 09 56 1.20) 5 11 16 49 1.22) 6 01 21 44 1.47) 2 05</p><p>3 7 4 3 </p><p>>24 333/ 179/ 1.11 (0.86- 0. 394/4 118/1 1.23 (0.91- 0.18 311/4 201/1 1.40 (1.08- 0.0 324/3 188/2 0.91 (0.71- 0.46</p><p>(mean) 419 199 1.44) 42 99 19 1.66) 3 27 91 1.82) 10 72 46 1.17) 4 </p><p>5</p><p>Menopausal status </p><p>Premenopa 682/ 385/ 1.06 (0.87- 0. 0.13 825/5 242/1 0.98 (0.78- 0.89 0. 664/4 403/2 1.12 (0.91- 0.28 0. 664/4 403/2 0.97 (0.79- 0.74 0.</p><p> usal 496 260 1.29) 58 9 82 74 1.24) 0 34 88 68 1.36) 3 52 73 83 1.18) 3 59</p><p>1 8 8 8 Postmenop 256/ 151/ 1.37 (1.02- 0. 318/4 89/10 1.17 (0.83- 0.36 256/3 151/1 1.15 (0.86- 0.33 225/3 182/2 1.30 (0.98- 0.06</p><p> ausal 381 162 1.84) 03 39 4 1.65) 1 67 76 1.54) 5 30 13 1.73) 7 </p><p>5 </p><p>BMIb, kg/m2</p><p>< 25 723/ 417/ 1.10 (0.91- 0. 0.63 891/6 249/1 1.02 (0.82- 0.83 0. 714/5 426/2 1.19 (0.98- 0.07 0. 678/5 462/3 1.07 (0.88- 0.49 0.</p><p>565 282 1.34) 32 3 65 82 1.28) 2 47 63 84 1.44) 7 70 18 29 1.29) 6 62</p><p>1 5 1 1 </p><p>≥ 25 204/ 115/ 1.28 (0.93- 0. 242/3 77/96 1.09 (0.76- 0.63 199/2 120/1 1.04 (0.76- 0.80 202/2 117/1 1.02 (0.75- 0.91</p><p>313 140 1.76) 13 57 1.56) 9 93 60 1.42) 4 85 68 1.39) 3 </p><p>4 </p><p>Histologyb</p><p>CINIII 100/ 60/4 1.17 (0.81- 0. 0.40 123/1, 37/27 1.08 (0.72- 0.70 0. 102/8 58/44 1.05 (0.73- 0.77 0. 96/80 64/49 1.09 (0.76- 0.64 0.</p><p>879 22 1.67) 41 9 023 8 1.64) 1 95 57 4 1.52) 9 93 4 7 1.55) 4 97</p><p>0 4 5 8 </p><p>SCC 733/ 431/ 1.17 (0.98- 0. 899/1, 265/2 1.05 (0.86- 0.62 724/8 440/4 1.16 (0.98- 0.08 702/8 462/4 1.04 (0.88- 0.66</p><p>879 422 1.40) 07 023 78 1.29) 3 57 44 1.39) 6 04 97 1.23) 5 </p><p>7 </p><p>Non- 108/ 49/4 0.82 (0.56- 0. 127/1, 30/27 0.87 (0.57- 0.54 99/85 58/44 1.09 (0.76- 0.65 96/80 61/49 0.99 (0.69- 0.96 squamous 879 22 1.20) 31 023 8 1.35) 0 7 4 1.56) 3 4 7 1.42) 4 </p><p>7 </p><p>FIGO stage</p><p>I 453/ 238/ 1.03 (0.84- 0. 0.32 539/1, 152/2 1.00 (0.79- 0.99 0. 430/8 261/4 1.14 (0.93- 0.21 0. 434/8 257/4 0.94 (0.77- 0.52 0.</p><p>879 422 1.26) 79 0 023 78 1.27) 5 73 57 44 1.39) 3 94 04 97 1.15) 5 11</p><p>5 4 6 1 </p><p>II 311/ 192/ 1.25 (0.99- 0. 389/1, 114/2 1.08 (0.83- 0.58 316/8 187/4 1.16 (0.93- 0.18 283/8 220/4 1.26 (1.01- 0.0</p><p>879 422 1.57) 05 023 78 1.40) 0 57 44 1.46) 7 04 97 1.57) 43 8 </p><p>III~IV 27/8 21/4 1.835 (0.94- 0. 35/1,0 13/27 1.28 (0.60- 0.52 29/85 19/44 1.12 (0.56- 0.75 32/80 16/49 0.79 (0.39- 0.52</p><p>79 22 3.57) 07 23 8 2.72) 9 7 4 2.21) 0 4 7 1.62) 3 </p><p>4 </p><p>Tumor size, cm</p><p>< 4 580/ 328/ 1.13 (0.94- 0. 0.69 707/1, 201/2 1.05 (0.85- 0.64 0. 558/8 350/4 1.21 (1.01- 0.0 0. 559/8 349/4 1.00 (0.83- 0.99 0.</p><p>879 422 1.36) 20 6 023 78 1.30) 9 69 57 44 1.46) 44 43 04 97 1.20) 4 48</p><p>6 6 9 9 </p><p>≥ 4 294/ 157/ 1.04 (0.82- 0. 346/1, 105/2 1.02 (0.78- 0.87 289/8 162/4 1.02 (0.80- 0.89 267/8 184/4 1.12 (0.89- 0.34</p><p>879 422 1.32) 73 023 78 1.34) 2 57 44 1.29) 7 04 97 1.41) 2 </p><p>0 </p><p>Pelvic LN</p><p>Negative 703/ 388/ 1.11 (0.93- 0. 0.80 850/1, 241/2 1.05 (0.86- 0.65 0. 687/8 404/4 1.14 (0.96- 0.14 0. 657/8 434/4 1.06 (0.89- 0.51 0.</p><p>879 422 1.33) 23 0 023 78 1.29) 2 50 57 44 1.36) 2 25 04 97 1.26) 8 51</p><p>5 2 6 8 </p><p>Positive 202/ 116/ 1.10 (0.83- 0. 241/1, 77/27 1.07 (0.78- 0.68 187/8 131/4 1.25 (0.96- 0.10 199/8 119/4 0.95 (0.73- 0.71</p><p>879 422 1.44) 51 023 8 1.45) 8 57 44 1.63) 2 04 97 1.25) 5 </p><p>4 </p><p>LVSI</p><p>Negative 530/ 309/ 1.14 (0.94- 0. 0.67 649/1, 190/2 1.05 (0.84- 0.69 0. 516/8 323/4 1.19 (0.98- 0.07 0. 503/8 336/4 1.06 (0.88- 0.56 0.</p><p>879 422 1.38) 18 1 023 78 1.30) 6 78 57 44 1.44) 5 89 04 97 1.27) 0 71</p><p>9 2 1 0 </p><p>Positive 267/ 146/ 1.10 (0.86- 0. 316/1, 97/27 1.09 (0.82- 0.55 252/8 161/4 1.18 (0.93- 0.18 253/8 160/4 1.03 (0.81- 0.79</p><p>879 422 1.41) 45 023 8 1.44) 0 57 44 1.50) 3 04 97 1.31) 6 </p><p>1 Depth of cervical stromal</p><p> invasion</p><p>≤ 1/2 419/ 246/ 1.19 (0.97- 0. 0.65 513/1, 152/2 1.08 (0.85- 0.51 0. 407/8 258/4 1.23 (1.00- 0.05 0. 401/8 264/4 1.05 (0.86- 0.60 0.</p><p>879 422 1.46) 10 4 023 78 1.37) 7 75 57 44 1.50) 0 62 04 97 1.29) 8 73</p><p>1 6 5 3 </p><p>> 1/2 466/ 257/ 1.09 (0.89- 0. 564/1, 159/2 1.00 (0.79- 0.99 454/8 269/4 1.11 (0.91- 0.32 444/8 279/4 1.01 (0.83- 0.95</p><p>879 422 1.33) 42 023 78 1.26) 2 57 44 1.35) 3 04 97 1.23) 6 </p><p>7 </p><p>ER- expression</p><p>Negative 482/ 263/ 1.11 (0.91- 0. 0.92 568/1, 177/2 1.12 (0.90- 0.30 0. 462/8 283/4 1.17 (0.96- 0.11 0. 456/8 289/4 1.01 (0.83- 0.91 0.</p><p>879 422 1.35) 30 2 023 78 1.41) 9 74 57 44 1.43) 3 07 04 97 1.23) 0 78</p><p>7 5 4 2 </p><p>Positive 41/8 23/4 0.95 (0.54- 0. 50/1,0 14/27 0.98 (0.52- 0.94 32/85 32/44 1.65 (0.97- 0.06 38/80 26/49 1.04 (0.61- 0.89</p><p>79 22 1.67) 86 23 8 1.85) 8 7 4 2.80) 3 4 7 1.78) 3 </p><p>0 </p><p>PR- expression</p><p>Negative 505/ 278/ 1.11 (0.91- 0. 0.62 596/1, 187/2 1.12 (0.90- 0.30 0. 475/8 308/4 1.23 (1.01- 0.03 0. 480/8 303/4 1.00 (0.82- 0.98 0.</p><p>879 422 1.35) 31 6 023 78 1.40) 5 32 57 44 1.49) 7 21 04 97 1.21) 2 45</p><p>5 8 5 4 </p><p>Positive 18/8 8/42 0.72 (0.28- 0. 22/1,0 4/278 0.74 (0.25- 0.58 19/85 7/444 0.52 (0.19- 0.19 14/80 12/49 1.48 (0.65- 0.35</p><p>79 2 1.83) 48 23 2.20) 6 7 1.41) 6 4 7 3.39) 5 </p><p>6 </p><p>BMI, body mass index; FIGO, International Federation of Gynecology and Obstetrics; CIN, cervical intraepithelial neoplasia; SCC, squamous cell carcinoma; LN, Lymph Node; LVSI, lymph-vascular space invasion. a Obtained in logistic regression models with adjustment for age, age at primiparity, menopausal status and BMI; b According to the current WHO recommendations;</p><p> hom Homogeneity test;</p><p>The results were in bold, if P < 0.05.</p>