Supplemental Tables Supplemental Table S1. The SNP rs2854744 is in Hardy-Weinberg equilibrium (HWE) in all study groups. Study groups Caucasians combined Hungary Germany combined East Germany West Germany combined Number of subjects with complete basis data (age, gender, smoking) HWE ² P value Status N Cases 1240 1192 0.9755 Controls 1318 1310 0.8999 Cases 222 0.6460 Controls 77 74 0.5589 Cases 970 0.9800 243 997 Controls 1241 1236 0.9777 Cases 212 212 0.9314 Controls 200 200 0.8384 Cases 758 0.9997 785 Controls 1041 1036 1.0000 Cases 387 381 0.9997 Controls 167 167 0.5656 Cases 398 377 0.9977 Controls 874 869 0.9033 DO - hospital Cases 87 86 0.6522 DO - occupational Cases 311 291 0.8330 DO - controls Controls 874 869 0.9033 Cases 98 0.1711 Controls 219 56 0.4451 Cases 112 112 0.0967 Controls 188 188 0.9177 W. Germany - ongoing W. Germany - industrial Pakistan Venezuela All combined Cases 98 1450 1402 0.6775 Controls 1725 1554 0.9978 1 Supplemental Table S2. Unadjusted ORs and 95% CIs for all relevant genetic models indicate minor effects in Hungarians, Pakistanis and Venezuelans but no reliable effect of rs2854744 A/A on bladder cancer. A. Results of the additive model with [A] as risk factor. Genotype frequency Additive model Study groups Status N C/C A/C A/A P value Caucasians combined Cases Controls 1234 1318 0.31 0.31 0.50 0.50 0.20 0.19 0.7987 Hungary Cases 237 0.28 0.53 0.20 0.3062 Controls 77 0.31 0.55 0.14 1.22 0.83 - 1.79 Cases 997 0.32 0.49 0.19 0.8372 Controls 1241 0.31 0.50 0.19 0.99 0.88 - 1.11 Cases 212 0.37 0.47 0.17 0.6832 Controls 200 0.34 0.51 0.16 0.94 0.71 - 1.25 Cases 785 0.30 0.50 0.20 0.8951 Controls 1041 0.30 0.49 0.20 1.01 0.88 - 1.15 Cases 387 0.28 0.50 0.22 0.9524 Controls 167 0.26 0.54 0.20 1.01 0.78 - 1.31 Cases 398 0.32 0.49 0.19 0.5627 0.95 0.80 - 1.13 Germany combined East Germany West Germany combined: W. Germany - ongoing W. Germany - industrial OR, 95% CI 1.02 0.91 - 1.14 Controls 874 0.31 0.49 0.20 hospitala Cases 87 0.31 0.45 0.24 0.5992 1.09 0.80 - 1.48 DO - occupationala Cases 311 0.32 0.50 0.17 0.3501 0.92 0.76 - 1.10 DO - controls Controls 874 0.31 0.49 0.20 Cases 98 0.37 0.40 0.23 0.0560 Controls 219 0.44 0.42 0.14 1.37 0.99 - 1.90 Cases Controls Cases 112 188 1450 0.40 0.37 0.32 0.38 0.49 0.48 0.21 0.14 0.20 0.6724 1.07 0.77 - 1.49 0.3734 1.05 0.95 - 1.16 Controls 1725 0.33 0.49 0.18 DO - Non Caucasian study groups Pakistan Venezuela All combined aControls are the Dortmund control group OR = odds ratio; 95% CI = 95% confidence intervals P values of the exact Cochran-Armitage trend test (2-sided), ORs and 95% CIs for the additive model are given. The combined Caucasian study groups have been adjusted for different regions (Hungary, East Germany, West Germany). All study groups combined have been adjusted for different ethnicities. 2 B. Results of the recessive model for [A] and the multiplicative model with [A] as risk factor. Genotype Recessive model Multiplicative model OR 95% CI 1.05 0.86 1.28 1.48 0.70 3.34 1.00 0.81 1.24 1.04 0.59 1.82 1.01 0.80 1.28 1.14 0.72 1.86 0.91 0.66 1.24 1.26 0.71 2.16 0.81 0.57 1.15 P value 1.86 0.97 3.53 1.63 0.84 3.12 1.12 0.94 1.34 0.0508 Study groups Status N A/A [A] P value Caucasians combined Cases Controls 1234 1318 0.20 0.19 0.44 0.44 0.6429 Hungary Cases 237 0.20 0.46 0.3158 Controls 77 0.14 0.42 Cases 997 0.19 0.44 Controls 1241 0.19 0.44 Cases 212 0.17 0.40 Controls 200 0.16 0.41 West Germany combined Cases 785 0.20 0.45 Controls 1041 0.20 0.45 W. Germany ongoing Cases 387 0.22 0.47 Controls 167 0.20 0.47 W. Germany industrial Cases 398 0.19 0.43 Controls 874 0.20 0.44 DO - hospitala Cases 87 0.24 0.47 0.4032 DO - occupationala Cases 311 0.17 0.42 0.2431 DO - controls Controls 874 0.20 0.44 Cases 98 0.23 0.43 Controls 219 0.14 0.35 Venezuela Cases Controls 112 188 0.21 0.14 0.41 0.39 0.1521 All combined Cases 1450 0.20 0.44 0.2062 Controls 1725 0.18 0.42 Germany combined East Germany 1.0000 0.8947 0.9530 0.5747 0.5434 0.7996 0.3531 0.8558 0.7227 0.9197 1.0000 0.5757 0.6316 0.3715 OR 95% CI 1.01 0.91 1.14 1.20 0.82 1.77 0.99 0.88 1.11 0.94 0.71 1.26 1.01 0.88 1.15 1.01 0.77 1.31 0.95 0.80 1.13 1.09 0.79 1.51 0.92 0.76 1.11 Non Caucasian study groups Pakistan aControls 0.0520 0.6670 0.3717 1.43 0.9951 2.0403 1.08 0.76 1.53 1.05 0.95 1.16 are the Dortmund control group OR = odds ratio; 95% CI = 95% confidence intervals P values of the exact chi-square test, ORs and 95% CIs for the recessive (A/A vs. A/C, C/C) and of the multiplicative ([A] vs. [C]) model are given. P values for combined Caucasian groups adjusted for region and P values for all study groups combined adjusted for ethnicity were calculated using the method of Mantel-Haenszel. Breslow-Day tests indicate the homogeneity of the ORs (recessive model: Caucasians combined P=0.6090, all combined P=0.0829; multiplicative model: Caucasians combined P=0.5800, all combined P=0.1717). 3 Supplemental Table S3. No effect of the rare [A] allele of the IGFBP3 SNP rs2854744 adjusted for age, gender and smoking habits. A. Adjusted P values, ORs and 95% CIs for the additive model. Study groups Status Caucasians combined Cases 1192 0.31 Controls 1310 0.31 0.50 0.50 0.20 0.19 0.8637 1.01 0.90 - 1.14 Hungary Cases 0.28 0.53 0.20 0.1200 Controls 74 0.31 0.55 0.14 1.41 0.92 - 2.16 Cases 0.32 0.49 0.19 0.8060 Controls 1236 0.31 0.50 0.19 0.98 0.87 - 1.12 Cases 0.7503 0.95 0.71 - 1.28 0.8527 0.99 0.86 - 1.14 0.7212 0.95 0.72 - 1.25 0.2890 0.90 0.75 - 1.09 Germany combined East Germany 222 970 Genotype frequency P value OR, 95% CI C/C A/C A/A 212 0.37 0.47 0.17 Controls 200 0.34 0.51 0.16 0.30 0.50 0.20 Controls 1036 0.30 0.49 0.20 Cases West Germany combined Cases W. Germany - ongoing N 758 381 0.28 0.50 0.22 Controls 167 0.26 0.54 0.20 Cases 377 0.32 0.49 0.19 Controls 869 0.31 0.49 0.20 DO - hospitala Cases 86 0.31 0.45 0.24 0.4024 1.15 0.83 - 1.61 DO - occupationala Cases 291 0.32 0.50 0.17 0.1074 0.84 0.68 - 1.04 DO - controls Controls 869 0.31 0.49 0.20 98 0.37 0.40 0.23 0.7960 Controls 56 0.44 0.42 0.14 0.94 0.58 - 1.52 Cases Controls Cases Controls 0.40 0.37 0.32 0.33 0.38 0.49 0.48 0.49 0.21 0.14 0.20 0.18 0.7262 1.09 0.67 - 1.77 0.6475 1.03 0.92 - 1.15 W. Germany - industrial Non Caucasian study groups Pakistan Venezuela All combined Cases 112 188 1402 1554 aControls are the Dortmund control group (DO controls) OR = odds ratio; 95% CI = 95% confidence intervals P values of the Wald test, ORs and 95% CIs for the additive model adjusted for age, gender and smoking habits are given. N denotes the number of observations used for the multivariable logistic regression model. The combined Caucasian study groups have been adjusted for different regions (Hungary, East Germany, West Germany). All study groups combined have been adjusted for different ethnicities. 4 B. Adjusted P values, ORs and 95% CIs for the recessive mode of inheritance for the risk allele [A] and the multiplicative model for the risk allele [A]. Multiplicative model A/A OR 95% CI 1.04 0.84 - 1.29 P value 1.86 0.84 - 4.12 0.1377 1.36 0.91 - 2.04 0.99 0.79 - 1.24 0.8060 0.98 0.87 - 1.12 1.15 0.66 - 2.01 0.7522 0.95 0.71 - 1.28 0.96 0.75 - 1.24 0.8528 0.99 0.86 - 1.14 1.04 0.65 - 1.66 0.7264 0.95 0.73 - 1.25 0.83 0.59 - 1.17 0.2870 0.90 0.74 - 1.09 1.38 0.79 - 2.41 0.71 0.48 - 1.05 0.3980 0.87 0.62 - 1.21 1.19 0.96 - 1.47 1.04 0.42 - 2.56 0.7871 0.93 0.56 - 1.55 1.69 0.70 - 4.06 0.7230 1.09 0.67 - 1.78 1.09 0.90 - 1.32 0.6474 1.03 0.92 - 1.15 Study groups Status Caucasians combined Cases 1192 0.20 0.44 0.7267 Controls 1310 0.19 0.44 Hungary Cases Germany combined N Genotype Recessive model 222 [A] P value 0.20 0.46 0.1286 Controls 74 0.14 0.42 Cases 0.19 0.44 0.9307 970 Controls 1236 0.19 0.44 East Germany Cases 212 0.17 0.40 0.6119 Controls 200 0.16 0.41 West Germany combined Cases 0.20 0.45 0.7644 W. Germany - ongoing Cases W. Germany - industrial 758 Controls 1036 0.20 0.45 381 0.22 0.47 0.8819 Controls 167 0.20 0.47 Cases 0.19 0.43 0.2880 377 Controls 869 0.20 0.44 hospitala Cases 86 0.24 0.47 0.2518 DO - occupationala Cases 291 0.17 0.42 0.0830 DO - controls Controls 869 DO - 0.8643 0.1073 OR 95% CI 0.99 0.88 - 1.12 0.20 0.44 Non Caucasian study groups Pakistan Venezuela All combined Cases 98 0.23 0.43 0.9288 Controls 56 0.14 0.35 Cases Controls Cases Controls 0.21 0.14 0.20 0.18 112 188 1402 1554 0.41 0.2428 0.39 0.44 0.3896 0.42 aControls are the Dortmund control group OR = odds ratio; 95% CI = 95% confidence intervals P values of the Wald test, ORs and 95% CIs for the recessive (A/A vs. A/C, C/C) and for the multiplicative ([A] vs. [C]) model, respectively, adjusted for age, gender and smoking habits are given. N denotes the number of observations used for the multivariable logistic regression model. The combined Caucasian study groups have been adjusted for different regions (Hungary, East Germany, West Germany). All study groups combined have been adjusted for different ethnicities. 5 Supplemental Table S4. No effect of the rare [A] allele of the IGFBP3 SNP rs2854744 on bladder cancer risk in subgroups of smokers and non-smokers nor differences between smokers and non-smokers in rs2854744 distribution. A. Frequencies of the genotypes and alleles of rs2854744 in non-smokers. Genotype Study groups Status N C/C Caucasians combined Cases 259 85 0.33 124 0.48 50 0.19 0.57 0.43 Controls 587 192 0.33 282 0.48 113 0.19 0.57 0.43 Cases 61 20 0.33 32 0.52 9 0.15 0.59 0.41 Controls 34 14 0.41 14 0.41 6 0.18 0.62 0.38 Cases 198 65 0.33 92 0.46 41 0.21 0.56 0.44 Controls 553 178 0.32 268 0.48 107 0.19 0.56 0.44 Cases 50 17 0.34 25 0.50 8 0.16 0.59 0.41 Controls 93 34 0.37 40 0.43 19 0.20 0.58 0.42 Cases 148 48 0.32 67 0.45 33 0.22 0.55 0.45 Controls 460 144 0.31 228 0.50 88 0.19 0.56 0.44 Cases 70 22 0.31 35 0.50 13 0.19 0.56 0.44 Controls 62 18 0.29 33 0.53 11 0.18 0.56 0.44 Cases 78 26 0.33 32 0.41 20 0.26 0.54 0.46 Controls 398 126 0.32 195 0.49 77 0.19 0.56 0.44 DO - hospital Cases 16 4 0.25 6 0.38 6 0.38 0.44 0.56 DO - occupational Cases 62 22 0.35 26 0.42 14 0.23 0.56 0.44 DO - controls Controls 398 126 0.32 195 0.49 77 0.19 0.56 0.44 Cases 33 11 0.33 11 0.33 11 0.33 0.50 0.50 Controls 8 1 0.13 4 0.50 3 0.38 0.38 0.63 Venezuela Cases 13 3 0.23 5 0.38 5 0.38 0.42 0.58 All combined Controls Cases 118 305 50 99 0.42 53 0.32 140 0.45 15 0.46 66 0.13 0.22 0.65 0.55 0.35 0.45 Controls 713 243 0.34 339 0.48 131 0.18 0.58 0.42 Hungary Germany combined East Germany West Germany combined W. Germany - ongoing W. Germany - industrial A/C Allele A/A [C] [A] Non Caucasian study group Pakistan 6 B. Unadjusted P values, ORs, 95% CIs of rs2854744 in non-smokers. Global Additive Recessive Study groups Status N P value P value P value Caucasians combined Cases 259 0.9494 0.7528 0.7718 Controls 587 Cases 61 0.5720 0.7096 0.7727 Controls 34 Cases 198 0.8721 0.9029 0.7549 Controls 553 Cases 50 0.6803 0.8821 0.6553 Controls 93 Cases 148 0.6000 0.7606 0.4088 Controls 460 Cases 70 0.9720 0.8958 1.0000 Controls 62 Cases 78 0.3403 0.6013 0.2197 Controls 398 DO - hospitala Cases 16 0.2188 0.1695 0.1043 DO - occupationala Cases 62 0.5831 0.9513 0.6069 DO - controls Controls 398 Cases 33 0.5439 0.4248 1.0000 Controls 8 Cases 13 0.0427 0.0283 0.0288 Controls 118 Cases 305 0.8753 0.7215 0.6093 Controls 713 Hungary Germany combined East Germany West Germany combined W. Germany - ongoing W. Germany - industrial OR 95% CI 1.06 0.721.55 0.81 0.233.06 1.09 0.711.65 0.74 0.261.97 1.21 0.751.94 1.06 0.402.86 1.44 0.772.60 2.50 0.727.85 1.22 0.592.38 Multiplicative P value 0.7504 0.7587 0.9061 0.9005 0.7879 0.9019 0.5981 0.2040 1.0000 OR 95% CI 1.04 0.831.29 1.12 0.592.16 1.01 0.801.29 0.96 0.571.62 1.04 0.791.37 0.97 0.581.62 1.10 0.771.57 1.65 0.763.63 0.99 0.661.47 Non Caucasian study groups Pakistan Venezuela All combined aControls 0.83 0.4148 0.136.39 4.29 0.0321 0.96 – 17.08 1.09 0.7174 0.771.54 0.60 0.162.09 2.51 1.026.33 1.04 0.851.26 are the Dortmund control group OR = odds ratio; 95% CI = 95% confidence intervals P values of the exact chi-square test for the genotype, recessive and multiplicative model, P values of the Cochran-Armitage trend test for the additive model, ORs and 95% CIs for the recessive and of the multiplicative model are given. The combined Caucasian study groups have been adjusted for different regions (Hungary, East Germany, West Germany). All study groups combined have been adjusted for different ethnicities. Breslow-Day tests indicate the homogeneity of the ORs (recessive model: Caucasians P=0.5591, all combined P=0.0633; multiplicative model: Caucasians P=0.9259, all combined P=0.0574). 7 C. Frequencies of the genotypes and alleles of rs2854744 in former smokers. Genotype Allele Study groups Status N C/C A/C A/A Caucasians combined Cases 581 165 0.28 299 0.51 117 0.20 0.54 0.46 Controls 503 154 0.31 252 0.50 97 0.19 0.56 0.44 Cases 80 16 0.20 42 0.53 22 0.28 0.46 0.54 Controls 26 8 0.31 16 0.62 2 0.08 0.62 0.38 Cases 501 149 0.30 257 0.51 95 0.19 0.55 0.45 Controls 477 146 0.31 236 0.49 95 0.20 0.55 0.45 Cases 103 38 0.37 47 0.46 18 0.17 0.60 0.40 Controls 88 27 0.31 50 0.57 11 0.13 0.59 0.41 Cases 398 111 0.28 210 0.53 77 0.19 0.54 0.46 Controls 389 119 0.31 186 0.48 84 0.22 0.54 0.46 Cases 220 57 0.26 113 0.51 50 0.23 0.52 0.48 Controls 68 19 0.28 37 0.54 12 0.18 0.55 0.45 Cases 178 54 0.30 97 0.54 27 0.15 0.58 0.42 Controls 321 100 0.31 149 0.46 72 0.22 0.54 0.46 DO - hospital Cases 24 6 0.25 12 0.50 6 0.25 0.50 0.50 DO - occupational Cases 154 48 0.31 85 0.55 21 0.14 0.59 0.41 DO - controls Controls 321 100 0.31 149 0.46 72 0.22 0.54 0.46 Cases 0 - - - - - - - - Controls 0 - - - - - - - - Venezuela Cases 42 14 0.33 18 0.43 10 0.24 0.55 0.45 All combined Controls Cases 35 623 7 179 0.20 20 0.29 317 0.57 8 0.51 127 0.23 0.20 0.49 0.54 0.51 0.46 Controls 538 161 0.30 272 0.51 105 0.20 0.55 0.45 Hungary Germany combined East Germany West Germany combined W. Germany - ongoing W. Germany - industrial [C] [A] Non Caucasian study groups Pakistan 8 D. Unadjusted P values, ORs, 95% CIs of rs2854744 in former smokers. Global Additive Recessive Study groups Status N P value P value P value Caucasians combined Cases 581 0.8292 0.5754 0.7771 Controls 503 Cases 80 0.1156 0.0441 0.0563 Controls 26 Cases 501 0.8533 0.9845 0.7466 Controls 477 Cases 103 0.2861 0.8998 0.9273 Controls 88 Cases 398 0.3815 0.9273 0.4797 Controls 389 Cases 220 0.6908 0.4579 0.4045 Controls 68 Cases 178 0.0999 0.3268 0.0606 Controls 321 DO - hospitala Cases 24 0.8569 0.5701 0.8009 DO - occupationala Cases 154 0.0565 0.2010 0.0261 DO - controls Controls 321 Cases 0 - - Controls 0 Cases 42 0.3805 0.4465 Hungary Germany combined East Germany West Germany combined W. Germany - ongoing W. Germany - industrial Multiplicative OR 95% CI 1.05 0.771.42 4.55 0.9842.51 0.94 0.681.31 1.48 0.623.70 0.87 0.611.25 1.37 0.663.04 0.62 0.371.03 1.15 0.363.17 0.55 0.310.95 P value - - - - 1.0000 1.05 0.32 3.55 1.06 0.791.41 0.5176 0.78 0.391.55 1.04 0.881.23 0.5808 0.0785 1.0000 0.9171 0.9596 0.4926 0.3520 0.6528 0.2096 OR 95% CI 1.05 0.881.25 1.86 0.943.73 1.00 0.831.20 0.97 0.631.50 1.01 0.821.24 1.15 0.771.73 0.88 0.671.15 1.19 0.632.24 0.84 0.631.11 Non Caucasian study groups Pakistan Venezuela All combined Controls 35 Cases 623 Controls 538 0.8816 aControls 0.6169 0.7150 0.6211 are the Dortmund control group Breslow-Day tests indicate the homogeneity of the ORs (recessive model: All combined P= 0.9990, Caucasians P=0.0525; multiplicative model: all combined P=0.3551, Caucasians P=0.1838). 9 E. Frequencies of the genotypes and alleles of rs2854744 in current smokers. Genotype Allele Study groups Status N C/C A/C Caucasians combined Cases 353 117 0.33 172 0.49 64 0.18 0.58 0.42 Controls 222 62 0.28 118 0.53 42 0.19 0.55 0.45 Cases 82 24 0.29 44 0.54 14 0.17 0.56 0.44 Controls 15 2 0.13 10 0.67 3 0.20 0.47 0.53 Cases 271 93 0.34 128 0.47 50 0.18 0.58 0.42 Controls 207 60 0.29 108 0.52 39 0.19 0.55 0.45 Cases 59 23 0.39 27 0.46 9 0.15 0.62 0.38 Controls 19 6 0.32 11 0.58 2 0.11 0.61 0.39 Cases 212 70 0.33 101 0.48 41 0.19 0.57 0.43 Controls 188 54 0.29 97 0.52 37 0.20 0.55 0.45 Cases 91 28 0.31 43 0.47 20 0.22 0.54 0.46 Controls 37 7 0.19 20 0.54 10 0.27 0.46 0.54 Cases 121 42 0.35 58 0.48 21 0.17 0.59 0.41 Controls 151 47 0.31 77 0.51 27 0.18 0.57 0.43 DO - hospital Cases 46 16 0.35 21 0.46 9 0.20 0.58 0.42 DO - occupational Cases 75 26 0.35 37 0.49 12 0.16 0.59 0.41 DO - controls Controls 151 47 0.31 77 0.51 27 0.18 0.57 0.43 Cases 65 25 0.38 28 0.43 12 0.18 0.60 0.40 Controls 48 19 0.40 22 0.46 7 0.15 0.63 0.38 Venezuela Cases 57 28 0.49 20 0.35 9 0.16 0.67 0.33 All combined Controls Cases 35 475 12 170 0.34 19 0.36 220 0.54 4 0.46 85 0.11 0.18 0.61 0.59 0.39 0.41 Controls 305 93 0.30 159 0.52 53 0.17 0.57 0.43 Hungary Germany combined East Germany West Germany combined W. Germany - ongoing W. Germany - industrial A/A [C] [A] Non Caucasian study groups Pakistan 10 F. Unadjusted P values, ORs, 95% CIs of rs2854744 in current smokers. Global Additive Recessive Study groups Status N P value P value P value Caucasians combined Cases 353 0.3309 0.3444 0.9943 Controls 222 Cases 82 0.4391 0.3083 1.0000 Controls 15 Cases 271 0.4549 0.3750 1.0000 Controls 207 Cases 59 0.7129 0.8810 0.7238 Controls 19 Cases 212 0.6435 0.5093 1.0000 Controls 188 Cases 91 0.3911 0.2232 0.6458 Controls 37 Cases 121 0.8233 0.6271 1.0000 Controls 151 DO - hospitala Cases 46 0.8337 0.8663 0.8285 DO - occupationala Cases 75 0.8611 0.5768 0.8522 DO - controls Controls 151 Cases 65 0.8772 0.7126 0.6218 Controls 48 Cases 57 0.2280 0.4858 0.7598 Controls 35 Cases 475 0.2264 0.3390 0.8564 Controls 305 Hungary Germany combined East Germany West Germany combined: W. Germany - ongoing W. Germany - industrial Multiplicative OR 95% CI 1.00 0.641.56 0.82 0.195.14 0.97 0.601.60 1.53 0.2715.86 0.98 0.581.66 0.76 0.292.07 0.96 0.491.89 1.12 0.422.72 0.87 0.381.93 P value 1.33 0.434.34 1.45 0.367.00 1.04 0.711.51 0.7828 0.3491 0.4256 0.3922 1.0000 0.5216 0.2697 0.6629 0.9047 0.6142 OR 95% CI 0.89 0.691.14 0.68 0.291.61 0.89 0.681.16 0.95 0.422.17 0.91 0.681.22 0.71 0.401.27 0.92 0.641.31 0.96 0.581.58 0.89 0.591.36 Non Caucasian study groups Pakistan Venezuela All combined aControls 0.5262 0.3394 1.11 0.621.98 0.80 0.411.56 0.90 0.741.11 are the Dortmund control group Breslow-Day tests indicate the homogeneity of the ORs (recessive model: All combined P=0.7176, Caucasians P=0.8405; multiplicative model: all combined P=0.6880, Caucasians P=0.7851). 11 G. Frequencies of the genotypes and alleles of rs2854744 in ever smokers (current and former smokers). Genotype Allele Study groups Status N C/C A/C A/A Caucasians combined Cases 934 282 0.30 471 0.50 181 0.19 0.55 0.45 Controls 725 216 0.30 370 0.51 139 0.19 0.55 0.45 Cases 162 40 0.25 86 0.53 36 0.22 0.51 0.49 Controls 41 10 0.24 26 0.63 5 0.12 0.56 0.44 Cases 772 242 0.31 385 0.50 145 0.19 0.56 0.44 Controls 684 206 0.30 344 0.50 134 0.20 0.55 0.45 Cases 162 61 0.38 74 0.46 27 0.17 0.60 0.40 Controls 107 33 0.31 61 0.57 13 0.12 0.59 0.41 Cases 610 181 0.30 311 0.51 118 0.19 0.55 0.45 Controls 577 173 0.30 283 0.49 121 0.21 0.55 0.45 Cases 311 85 0.27 156 0.50 70 0.23 0.52 0.48 Controls 105 26 0.25 57 0.54 22 0.21 0.52 0.48 Cases 299 96 0.32 155 0.52 48 0.16 0.58 0.42 Controls 472 147 0.31 226 0.48 99 0.21 0.55 0.45 DO - hospital Cases 70 22 0.31 33 0.47 15 0.21 0.55 0.45 DO - occupational Cases 229 74 0.32 122 0.53 33 0.14 0.59 0.41 DO - controls Controls 472 147 0.31 226 0.48 99 0.21 0.55 0.45 Cases 65 25 0.38 28 0.43 12 0.18 0.60 0.40 Controls 48 19 0.40 22 0.46 7 0.15 0.63 0.38 Venezuela Cases 99 42 0.42 38 0.38 19 0.19 0.62 0.38 All combined Controls Cases 70 19 1098 349 0.27 39 0.32 537 0.56 12 0.49 212 0.17 0.19 0.55 0.56 0.45 0.44 Controls 843 0.30 431 0.51 158 0.19 0.56 0.44 Hungary Germany combined East Germany West Germany combined W. Germany - ongoing W. Germany - industrial [C] [A] Non Caucasian study groups Pakistan 254 12 H. Unadjusted P values, ORs, 95% CIs of rs2854744 in ever smokers (current and former smokers). Global Additive Recessive Multiplicative Study groups Status N P value P value P value P value OR 95% CI OR 95% CI Caucasians combined Cases 934 0.8807 0.8731 0.8611 0.8747 Controls 725 Cases 162 0.3409 0.4050 0.1934 Controls 41 Cases 772 0.8538 0.5776 0.7388 Controls 684 Cases 162 0.1847 0.7853 0.3821 Controls 107 Cases 610 0.7296 0.7462 0.5148 Controls 577 Cases 311 0.7839 0.8975 0.7870 Controls 105 Cases 299 0.2276 0.2556 0.0915 Controls 472 DO - hospitala Cases 70 1.0000 0.9852 1.0000 DO - occupationala Cases 229 0.1045 0.1689 0.0395 1.02 0.791.32 2.06 0.737.19 0.95 0.721.24 1.45 0.683.22 0.90 0.671.21 1.10 0.621.98 0.72 0.481.07 1.03 0.521.94 0.63 0.400.99 0.99 0.861.14 1.22 0.732.05 0.96 0.831.11 0.95 0.661.38 0.97 0.831.15 0.98 0.711.36 0.89 0.721.10 1.00 0.691.46 0.85 0.681.08 DO - controls Controls 472 Cases 65 0.8772 0.7126 0.6218 0.7828 Controls 48 Cases Controls 99 0.0658 0.2367 0.8410 Cases 1098 0.6305 0.7508 0.7483 Controls 843 1.33 0.434.34 1.15 0.482.81 1.04 0.831.31 Hungary Germany combined East Germany West Germany combined W. Germany - ongoing W. Germany - industrial 0.4594 0.6007 0.8573 0.7727 0.9364 0.2688 1.0000 0.1867 Non Caucasian study groups Pakistan Venezuela All combined 70 aControls 0.2619 0.7525 1.11 0.621.98 0.76 0.481.21 0.98 0.861.11 are the Dortmund control group Breslow-Day tests indicate the homogeneity of the ORs (recessive model: All combined P=0.8516, Caucasians P=0.1690; multiplicative model: all combined P= 0.4652, Caucasians P= 0.6806). 13 I. No difference in the distribution of rs2854744 A/A genotypes between smokers and non-smokers. Study groups Caucasians combined Hungary Germany combined Status Smoking habits N Cases Smokers Non-smokers Controls Smokers Non-smokers Cases Smokers Non-smokers Controls Smokers Non-smokers Cases Smokers Non-smokers 934 259 725 587 162 61 41 34 772 198 Genotype C/C A/C 0.30 0.50 0.33 0.48 0.30 0.51 0.33 0.48 0.25 0.53 0.33 0.52 0.24 0.63 0.41 0.41 0.31 0.50 0.33 0.46 A/A 0.19 0.19 0.19 0.19 0.22 0.15 0.12 0.18 0.19 0.21 Global P value (recessive model) 0.6776 (0.9933)1 0.4823 (0.9524)2 0.3281 (0.2633) 0.1905 (0.5317) 0.6769 (0.5445) Controls Smokers 684 0.30 0.50 0.20 0.7273 Non-smokers 553 0.32 0.48 0.19 (0.9425) East Germany Cases Smokers 162 0.38 0.46 0.17 0.8441 Non-smokers 50 0.34 0.50 0.16 (1.0000) Controls Smokers 107 0.31 0.57 0.12 0.1015 Non-smokers 93 0.37 0.43 0.20 (0.1249) West Germany combined Cases Smokers 610 0.30 0.51 0.19 0.4603 Non-smokers 148 0.32 0.45 0.22 (0.4232) Controls Smokers 577 0.30 0.49 0.21 0.7441 Non-smokers 460 0.31 0.50 0.19 (0.4838) W. Germany - ongoing Cases Smokers 311 0.27 0.50 0.23 0.6744 Non-smokers 70 0.31 0.50 0.19 (0.5249) Controls Smokers 105 0.25 0.54 0.21 0.8050 (0.6904) Non-smokers 62 0.29 0.53 18 W. Germany - industrial Cases Smokers 299 0.32 0.52 0.16 0.0943 Non-smokers 78 0.33 0.41 0.26 (0.0677) Controls Smokers 472 0.31 0.48 0.21 0.8456 Non-smokers 398 0.32 0.49 0.19 (0.5548) DO - hospital Cases Smokers 70 0.31 0.47 0.21 0.4061 Non-smokers 16 0.25 0.38 0.38 (0.2038) DO - occupational Cases Smokers 229 0.32 0.53 0.14 0.1860 Non-smokers 62 0.35 0.42 0.23 (0.1717) DO - controls Controls Smokers 472 0.31 0.48 0.21 0.8456 Non-smokers 398 0.32 0.49 0.19 (0.5548) Non Caucasian study groups Pakistan Cases Smokers 65 0.38 0.43 0.18 0.2780 Non-smokers 33 0.33 0.33 0.33 (0.1311) Controls Smokers 48 0.40 0.46 0.15 0.1832 Non-smokers 8 0.13 0.50 0.38 (0.1428) Venezuela Cases Smokers 99 0.42 0.38 0.19 0.2389 Non-smokers 13 0.23 0.38 0.38 (0.1474) Controls Smokers 70 0.27 0.56 0.17 0.1209 Non-smokers 118 0.42 0.45 0.13 (0.5192) All combined Cases Smokers 1098 0.32 0.49 0.19 0.5700 Non-smokers 305 0.32 0.46 0.22 (0.3857)3 Controls Smokers 843 0.30 0.51 0.19 0.2481 Non-smokers 713 34 0.48 0.18 (0.9871)4 P values of the exact chi-square test for global differences between ever smokers and non smokers are given. P values of the exact chi-square test for a different A/A distribution between ever smokers and non smokers are given in parenthesis. P values for combined Caucasian groups adjusted for region and P values for all study groups combined adjusted for ethnicity were calculated using the method of Mantel-Haenszel. 14 1Breslow-Day test for homogeneity of the ORs in the Caucasian case group P=0.3331 test for homogeneity of the ORs in the Caucasian case group P=0.1726 3Breslow-Day test for homogeneity of the ORs in the case group P=0.1163 4Breslow-Day test for homogeneity of the ORs in the case group P=0.2060 2Breslow-Day 15 Supplemental Table S5. No association between rs2854744 and urinary bladder cancer carcinogens. A. No difference in the distribution of rs2854744 between individuals exposed and non exposed to urinary bladder carcinogens. Exposure Genotype Study groups Status All combined Cases PAH East Germany W. Germany occupational All combined AA East Germany W. Germany occupational W. Germany - hospital All combined exposed not exposed Cases exposed not exposed Controls exposed 74 299 30 99 0.41 0.33 29 154 0.39 0.52 15 46 0.20 0.15 0.40 0.41 18 169 9 63 0.50 0.37 6 79 0.33 0.47 3 27 0.17 0.16 0.33 0.39 2 1 0.50 0 0.00 1 0.50 0.50 not exposed exposed 196 65 0.33 100 0.51 31 0.16 0.41 56 21 0.38 23 0.41 12 0.21 0.42 not exposed Cases exposed not exposed Cases exposed not exposed Controls exposed not exposed Cases exposed 130 36 0.28 75 0.58 19 0.15 0.43 131 328 40 115 0.31 0.35 67 155 0.51 0.47 24 58 0.18 0.18 0.44 0.41 13 175 3 69 0.23 0.39 6 79 0.46 0.45 4 27 0.31 0.15 0.54 0.38 2 196 1 65 0.50 0.33 0 100 0.00 0.51 1 31 0.50 0.16 0.50 0.41 118 37 0.31 61 0.52 20 0.17 0.43 not exposed Cases exposed not exposed Cases exposed not exposed Cases exposed not exposed Controls exposed 68 20 0.29 37 0.54 11 0.16 0.43 0 85 26 0.31 39 0.46 20 0.24 0.46 165 302 56 98 0.34 0.32 82 147 0.50 0.49 27 57 0.16 0.19 0.41 0.43 34 162 16 55 0.47 0.34 13 79 0.38 0.49 5 28 0.15 0.17 0.34 0.42 PAH or AA W. Germany occupational Cases W. Germany - hospital Cases All combined Cases East Cases A/A 0.0657 (0.3156; 0.5469) 0.5076 (1.0000; 0.5902) - C/C AD East Germany A/C Global P value (recessive model; multiplicati ve model) N Cases Exposure Freq. [A] 0.1137 (0.2856; 0.8201) 0.7296 (0.4300; 0.5215) 0.3146 (0.2344; 0.1440) - 0.9362 (1.0000; 0.9139) - 0.6868 (0.7531; 0.4520) 0.3713 (0.8066; 0.2769) 22 9 0.41 10 0.45 3 0.14 0.36 not exposed exposed 175 58 0.33 89 0.51 28 0.16 0.41 124 37 0.30 66 0.53 21 0.17 0.44 not exposed exposed not exposed exposed not exposed exposed 62 20 0.32 32 0.52 10 0.16 0.42 7 78 3 23 0.43 0.29 3 36 0.43 0.46 1 19 0.14 0.24 0.36 0.47 - 177 196 60 69 0.34 0.35 85 98 0.48 0.50 32 29 0.18 0.15 0.42 0.40 31 12 0.39 12 0.39 7 0.23 0.42 0.2709 (0.3375; 0.9050) 0.5424 16 0.7871 (1.0000; 0.6260) 0.9551 (1.0000; 0.8244) Germany PAH, AA or AD W. Germany occupational All combined East Germany PAH or ever smoking W. Germany occupational All combined East Germany W. Germany occupational not exposed Controls exposed not exposed Cases exposed not exposed Cases exposed not exposed Cases exposed not exposed Controls exposed not exposed Cases exposed not exposed Cases exposed not exposed Cases exposed not exposed Controls exposed not exposed Cases exposed 156 60 0.38 73 0.47 23 0.15 0.38 2 196 1 65 0.50 0.33 0 100 0.00 0.51 1 31 0.50 0.16 0.50 0.41 146 40 48 9 0.33 0.23 73 25 0.50 0.63 25 6 0.17 0.15 0.42 0.46 230 141 77 48 0.33 0.34 113 71 0.49 0.50 40 22 0.17 0.16 0.42 0.41 60 125 25 43 0.42 0.34 24 62 0.40 0.50 11 20 0.18 0.16 0.38 0.41 23 173 9 57 0.39 0.33 10 89 0.43 0.51 4 27 0.17 0.16 0.39 0.41 170 16 52 5 0.31 0.31 89 9 0.52 0.56 29 2 0.17 0.13 0.43 0.41 408 66 144 20 0.35 0.30 199 33 0.49 0.50 65 13 0.16 0.20 0.40 0.45 168 39 65 12 0.39 0.31 75 20 0.45 0.51 28 7 0.17 0.18 0.39 0.44 107 93 33 34 0.31 0.37 61 40 0.57 0.43 13 19 0.12 0.20 0.41 0.42 240 79 0.33 124 0.52 37 0.15 0.41 (0.2882; 0.6688) - 0.3647 (0.8164; 0.5260) 0.4851 (0.5618; 0.8109) 0.5124 (0.8338; 0.7339) 0.7897 (1.0000; 0.8736) 0.9413 (0.7460; 0.8530) 0.5868 (0.4602; 0.3024) 0.6448 (1.0000; 0.5212) 0.1015 (0.1249; 0.8388) 0.6766 (0.4054; 0.5608) PAH. AA, AD or ever smoking PAH, AA or ever smoking not 27 8 0.30 13 0.48 6 0.22 0.46 exposed All combined Cases exposed 426 150 0.35 206 0.48 70 0.16 0.41 0.5102 (0.9908; not 48 14 0.29 26 0.54 8 0.17 0.44 0.4549) exposed East Cases exposed 170 65 0.38 76 0.45 29 0.17 0.39 0.7623 Germany (1.0000; not 37 12 0.32 19 0.51 6 0.16 0.42 0.6963) exposed Controls exposed 107 33 0.31 61 0.57 13 0.12 0.41 0.1015 (0.1249; not 93 34 0.37 40 0.43 19 0.20 0.42 0.8388) exposed W. Germany Cases exposed 256 85 0.33 130 0.51 41 0.16 0.41 0.5891 (1.0000; not 11 2 0.18 7 0.64 2 0.18 0.50 occupational 0.5092) exposed All combined Cases exposed 437 152 0.35 213 0.49 72 0.16 0.41 0.6109 (0.9155; not 37 11 0.30 20 0.54 6 0.16 0.43 0.5743) exposed East Cases exposed 174 66 0.38 79 0.45 29 0.17 0.39 0.7194 Germany (1.0000; not 33 10 0.30 17 0.52 6 0.18 0.44 0.4963) exposed Controls exposed 118 37 0.31 65 0.55 16 0.14 0.41 0.2763 (0.3271; not 82 30 0.37 36 0.44 16 0.20 0.41 1.0000) exposed W. Germany Cases exposed 263 86 0.33 134 0.51 43 0.16 0.42 not 4 1 0.25 3 0.48 0 0.00 0.38 occupational exposed PAH: polycyclic aromatic hydrocarbons, AA: aromatic amines, AD: azo dyes Freq.: Frequency P values of the exact chi-square test for global differences between exposed and non exposed persons are given. P values of the exact chi-square test for a different A/A distribution between exposed and not exposed persons (recessive model) as well as P values of the exact chi-square test of a different allele distribution (multiplicative model) are given in parenthesis. P values for combined case groups were calculated using the method of Mantel-Haenszel. 17 B. No differences between cases and controls in the subgroups of exposed and not PAH Exposure exposed persons. Study groups All combined (East Germany, W.Germany – occupational) exposed not exposed exposed East Germany AA Exposure All combined (East Germany, W. Germany – occupational, W. Germany – hospital) not exposed exposed not exposed exposed East Germany AD not exposed All combined (East Germany, W. Germany – occupational, W. Germany – hospital) Status N Global A/A Recessive Multiplicative [A] allele P value genotype model model frequency (additive frequency P value P value model) Cases 74 Controls 2 Cases 299 Controls 196 0.20 0.50 0.15 0.16 0.40 0.50 0.41 0.41 Cases 18 Controls 2 Cases 169 0.17 0.50 0.16 0.33 0.50 0.39 Controls 196 0.16 0.41 Cases 131 0.18 0.44 Controls 2 0.50 0.50 Cases 328 0.18 0.41 Controls 31 0.16 0.41 Cases 13 0.31 0.54 Controls 2 0.50 0.50 Cases 175 0.15 0.38 Controls 196 0.16 0.41 Cases 165 0.16 0.41 Controls 22 0.14 0.36 Cases 302 0.19 0.43 Controls 175 0.16 0.41 exposed not exposed Cases 34 0.15 0.34 Controls 22 0.14 0.36 Cases 162 0.17 0.42 Controls 175 0.16 0.41 exposed - - - 0.9918 (1.0000) 0.8997 1.0000 - - - 0.6846 (0.5945) 1.0000 0.5973 - - - 0.6976 (1.0000) 0.6316 1.0000 - - - 0.4406 (0.3669) 1.0000 0.3680 0.8236 (0.6226) 0.7780 0.6250 0.7387 (0.6328) 0.4585 0.6344 0.9302 (0.8490) 1.0000 0.8404 0.9242 (1.0000) 0.7714 1.0000 - - - 0.8966 (0.7099) 0.8886 0.7161 - - - 0.5865 (0.3903) 0.8818 0.3955 0.9163 (0.7564) 1.0000 0.7558 0.9875 (0.9334) 1.0000 0.9350 East Germany PAH or AA not exposed All combined (East Germany, W.Germany – occupational) exposed not exposed exposed East Germany PAH, AA or AD not exposed All combined (East Germany, W.Germany – occupational) exposed not exposed exposed East Germany not Cases 177 0.18 0.42 Controls 2 0.50 0.50 Cases 196 Controls 196 Cases 31 0.15 0.16 0.23 0.40 0.41 0.42 Controls 2 0.50 0.50 Cases 156 0.15 0.38 Controls 196 0.16 0.41 Cases 230 Controls 23 Cases 141 0.17 0.17 0.16 0.42 0.39 0.41 Controls 173 Cases 60 0.16 0.18 0.41 0.38 Controls 23 0.17 0.39 1.0000 (1.0000) 1.0000 1.0000 Cases 125 0.16 0.41 0.9482 1.0000 0.9328 18 PAH, AA, AD or ever smoking PAH, AA or ever smoking PAH or ever smoking exposed All combined (East Germany, W.Germany – occupational) exposed not exposed exposed East Germany All combined (East Germany, W.Germany – occupational) not exposed exposed not exposed exposed East Germany All combined (East Germany, W.Germany – occupational) not exposed exposed not exposed exposed East Germany not exposed (0.9314) Controls 173 0.16 0.41 Cases 408 Controls 107 0.16 0.12 0.40 0.41 0.2946 (0.9363) 0.3671 0.9377 0.6322 (0.6581) 1.0000 0.6470 0.3857 0.7211 0.8148 0.8915 0.2538 (1.0000) 0.3006 1.0000 0.4789 (0.8050) 0.6572 0.8001 0.1351 (0.7869) 0.3049 0.7897 0.6922 (1.0000) 0.6328 1.0000 0.4690 (1.0000) 0.4810 1.0000 0.6106 (0.8897) 0.8010 0.8873 0.2821 (0.7278) 0.5123 0.7308 0.7684 (0.7760) 1.0000 0.7689 Cases 66 0.20 0.45 Controls Cases Controls Cases Controls Cases Controls Cases 93 168 107 39 93 426 107 48 0.20 0.17 0.12 0.18 0.20 0.16 0.12 0.17 0.42 0.39 0.41 0.44 0.42 0.41 0.41 0.44 Controls 93 0.20 0.42 Cases 170 Controls 107 Cases 37 0.17 0.12 0.16 0.39 0.41 0.42 Controls 93 0.20 0.42 Cases 437 Controls 118 Cases 82 0.16 0.14 0.20 0.41 0.41 0.43 Controls 37 0.16 0.41 Cases 174 Controls 118 Cases 33 0.17 0.14 0.18 0.39 0.41 0.44 Controls 0.20 0.41 82 0.1384 (0.7171) 0.6795 (0.8956) PAH: polycyclic aromatic hydrocarbons, AA: aromatic amines, AD: azo dyes P values of the exact chi-square test for global differences between cases and controls. Exact P values of the Cochran-Armitage trend test (additive model) are given in parenthesis. P values of the exact chi-square test for a different A/A distribution between cases and controls (recessive model) as well as P values of the exact chisquare test of a different allele distribution (multiplicative model). 19 Supplemental Table S6. Study group characteristics A. Distribution of gender in the study groups. Study groups P value Frequency males Frequency males cases N controls % N % Caucasians combined 5.540E-28 991 0.80 791 0.60 Hungary 0.0573 146 0.60 56 0.73 Germany combined 6.368E-40 845 0.85 735 0.59 East Germany 1.0000 182 0.86 171 0.86 West Germany combined 9.053E-43 663 0.84 564 0.54 West Germany – ongoing 0.1584 302 0.78 121 0.72 West Germany – industrial 1.438E-42 361 0.91 443 0.51 DO - hospitala 1.518E-09 73 0.84 DO - occupationala 2.264E-38 288 0.93 443 0.51 DO - controls Non Caucasian study groups Pakistan 0.2066 85 0.87 95 0.80 Venezuela 8.065E-07 79 0.71 77 0.41 All combined 2.668E-34 1155 0.80 963 0.60 For 101 persons gender was unknown. P value of the exact chi-square test 20 B. Distribution of age at diagnosis (cases) and at examination (controls), respectively, in the study groups. Study groups Status Caucasians combined Cases Hungary Germany combined East Germany West Germany combined West Germany – ongoing N Min Max Median Mean Standard P value deviation 1233 20.1 95.2 67.1 66.3 11.5 0.7039 Controls 1315 20.2 99.1 67.6 65.1 13.3 Cases 27.2 95.1 70.5 69.0 11.2 Controls 76 30.0 84.2 63.5 63.4 12.7 Cases 20.1 95.2 66.2 65.6 11.5 Controls 1239 20.2 99.1 67.7 6.52 13.4 Cases 240 993 212 20.1 91.3 65.6 65.0 11.2 Controls 200 29.4 91.2 67.7 67.5 10.2 Cases 26.1 95.2 66.3 65.8 11.5 Controls 1039 20.2 99.1 67.7 64.8 13.8 Cases 781 0.0022 0.1989 0.0201 0.7845 386 26.1 95.2 71.4 69.7 11.1 Controls 167 21.7 99.1 66.9 64.4 15.4 Cases 395 32.1 84.4 61.9 61.9 10.6 Controls 872 20.2 93.9 67.8 64.9 13.5 Dortmund - hospital Cases 86 44.8 83.9 67.8 67.0 9.4 0.5600 Dortmund - occupational Cases 309 32.1 84.4 60.8 60.5 10.5 <0.0001 Dortmund controls Controls 872 20.2 93.9 67.8 64.9 13.5 24.0 82.0 60.5 59.1 13.3 26.0 76.0 56.0 54.1 13.9 Cases 112 29.3 87.1 59.1 Controls 188 20.0 90.5 30.8 Cases 1443 20.1 95.2 66.2 60.2 36.3 65.3 11.8 15.6 11.9 Controls 1622 20.0 99.1 65.3 61.0 16.6 West Germany - industrial 0.0002 <0.0001 Non Caucasian study groups Pakistan Cases 98 Controls 119 Venezuela All combined For 7 cases and 103 controls age was unknown. P value of the Wilcoxon rank sum test. 21 0.0145 <0.0001 <0.0001 C. Frequency of non smokers, former smokers and current smokers in the study groups. Smoking habits Study groups Status Caucasians combined Cases 1193 Controls 1312 0.22 0.45 0.49 0.38 0.30 0.17 Hungary Cases 0.27 0.36 0.37 Controls 75 0.45 0.35 0.20 Cases 0.20 0.52 0.28 Controls 1237 0.45 0.39 0.17 Cases 212 0.24 0.49 0.28 Controls 200 0.47 0.44 0.10 Cases 0.20 0.53 0.28 Controls 1037 0.44 0.38 0.18 Cases 381 0.18 0.58 0.24 Controls 167 0.37 0.41 0.22 Cases 377 0.21 0.47 0.32 Controls 870 0.46 0.37 0.17 Dortmund – hospital Cases 86 0.19 0.28 0.53 Dortmund – occupational Cases 291 0.21 0.53 0.26 Dortmund controls Controls 870 0.46 0.37 0.17 98 0.34 0.00 0.66 Controls 56 0.14 0.00 0.86 Cases Controls Cases Controls 0.12 0.63 0.22 0.46 0.38 0.19 0.44 0.35 0.51 0.19 0.34 0.20 Germany combined East Germany West Germany combined West Germany – ongoing West Germany – industrial N Non smokers Former smokers Current smokers 223 970 758 Non Caucasian study groups: Pakistan Venezuela All combined Cases 112 188 1403 1556 For 216 subjects smoking habits were unknown. 22