1
Selinski et al. (2012) UGT1A genetic variant confers bladder cancer risk
SupplementalTables S1-S5
Supplemental Table S1.Study group characteristics
A. Distribution of gender in the study groups.
Study groups / Freq malescases / Freq males
controls
N / % / N / %
Caucasians combined / 1274 / 0.80 / 1070 / 0.62
Caucasians combined without East Germany / 1087 / 0.79 / 893 / 0.59
Hungary / 148 / 0.60 / 57 / 0.73
Germany combined / 1126 / 0.84 / 1013 / 0.62
East Germany / 487 / 0.86 / 177 / 0.83
West Germany combined / 939 / 0.83 / 836 / 0.58
West Germany – ongoing / 496 / 0.77 / 369 / 0.70
West Germany - industrial / 443 / 0.92 / 467 / 0.51
DO - hospital / 97 / 0.87
DO - occupational / 346 / 0.93
DO - controls / 467 / 0.51
Non Caucasian study groups
Pakistan / 88 / 0.87 / 99 / 0.80
Venezuela / 79 / 0.71 / 78 / 0.41
All combined / 1441 / 0.80 / 1247 / 0.61
All combined without East Germany / 1254 / 0.79 / 1070 / 0.59
For 103 persons gender was unknown.
B. Distribution of age at diagnosis (cases) and at examination (controls), respectively, in the study groups.
Study groups / Status / N / Min / Max / Median / Mean / Standard deviationCaucasians combined / Cases / 1586 / 20.1 / 95.2 / 67.7 / 66.7 / 11.4
Controls / 1724 / 20.1 / 100.0 / 66.9 / 63.4 / 15.3
Caucasians combinedwithout East Germany / Cases / 1368 / 26.1 / 95.2 / 68.0 / 67.0 / 11.4
Controls / 1512 / 20.1 / 100.0 / 66.9 / 62.8 / 15.8
Hungary / Cases / 242 / 27.2 / 95.1 / 70.5 / 69.0 / 11.2
Controls / 77 / 30.0 / 84.2 / 63.4 / 63.5 / 12.8
Germany combined / Cases / 1344 / 20.1 / 95.2 / 67.3 / 66.3 / 11.4
Controls / 1647 / 20.1 / 100.0 / 67.0 / 63.4 / 15.4
East Germany / Cases / 218 / 20.1 / 91.3 / 65.7 / 65.0 / 11.3
Controls / 212 / 29.4 / 91.2 / 67.8 / 67.8 / 10.2
West Germany combined / Cases / 1126 / 26.1 / 95.2 / 67.6 / 66.5 / 11.4
Controls / 1435 / 20.1 / 100.0 / 66.9 / 62.7 / 16.0
W. Germany - ongoing / Cases / 646 / 26.1 / 95.2 / 71.3 / 69.8 / 10.9
Controls / 524 / 20.5 / 100.0 / 61.8 / 59.2 / 18.6
W. Germany - industrial / Cases / 480 / 32.1 / 84.4 / 62.4 / 62.1 / 10.4
Controls / 911 / 20.1 / 93.9 / 67.9 / 64.7 / 13.8
DO - hospital / Cases / 111 / 44.8 / 83.9 / 67.3 / 66.9 / 9.3
DO - occupational / Cases / 369 / 32.1 / 84.4 / 61.0 / 60.7 / 10.3
DO - controls / Controls / 911 / 20.1 / 93.9 / 67.9 / 64.7 / 13.8
Non Caucasian study groups
Pakistan / Cases / 101 / 24.0 / 82.0 / 61.0 / 59.3 / 13.3
Controls / 124 / 26.0 / 76.0 / 56.0 / 54.2 / 13.8
Venezuela / Cases / 112 / 29.3 / 87.1 / 59.1 / 60.2 / 11.8
Controls / 190 / 20.0 / 90.5 / 30.6 / 36.1 / 15.6
All combined / Cases / 1799 / 20.1 / 95.2 / 67.1 / 65.9 / 11.7
Controls / 2038 / 20.0 / 100.0 / 64.9 / 60.3 / 17.2
All combinedwithout East Germany / Cases / 1581 / 24.0 / 95.2 / 67.4 / 66.0 / 11.8
Controls / 1826 / 20.0 / 100.0 / 64.3 / 59.4 / 17.7
For 109 subjects age was unknown.
C. Frequency of non-smokers, former smokers and current smokers in the study groups.
Study groups / Status / N / Non-smokers / Former smokers / Current smokersCaucasians combined / Cases / 1491 / 0.22 / 0.50 / 0.29
Controls / 1702 / 0.44 / 0.38 / 0.18
Caucasians combined
without East Germany / Cases / 1274 / 0.21 / 0.50 / 0.29
Controls / 1502 / 0.43 / 0.37 / 0.20
Hungary / Cases / 225 / 0.27 / 0.36 / 0.37
Controls / 76 / 0.46 / 0.33 / 0.21
Germany combined / Cases / 1266 / 0.21 / 0.52 / 0.27
Controls / 1626 / 0.44 / 0.38 / 0.18
East Germany / Cases / 217 / 0.23 / 0.48 / 0.29
Controls / 200 / 0.47 / 0.44 / 0.10
West Germany combined / Cases / 1049 / 0.20 / 0.53 / 0.27
Controls / 1426 / 0.43 / 0.37 / 0.19
W. Germany - ongoing / Cases / 624 / 0.19 / 0.57 / 0.24
Controls / 520 / 0.38 / 0.38 / 0.23
W. Germany - industrial / Cases / 425 / 0.21 / 0.47 / 0.32
Controls / 906 / 0.46 / 0.37 / 0.17
DO - hospital / Cases / 91 / 0.18 / 0.26 / 0.56
DO - occupational / Cases / 334 / 0.22 / 0.52 / 0.26
DO - controls / Controls / 906 / 0.46 / 0.37 / 0.17
Non Caucasian study groups
Pakistan / Cases / 101 / 0.34 / 0.00 / 0.66
Controls / 60 / 0.15 / 0.00 / 0.85
Venezuela / Cases / 112 / 0.12 / 0.38 / 0.51
Controls / 190 / 0.63 / 18 / 0.19
All combined / Cases / 1704 / 0.22 / 0.46 / 0.33
Controls / 1952 / 0.45 / 0.35 / 0.20
All combined
without East Germany / Cases / 1487 / 0.21 / 0.46 / 0.33
Controls / 1752 / 0.45 / 0.34 / 0.22
Frequency of non-smokers, former smokers and current smokers in the study groups.
For 290 subjects smoking habits were unknown.
Supplemental Table S2. The SNP rs11892031 is in Hardy-Weinberg equilibrium (HWE) in all study groups.
Study groups / Status / N / N* / HWE P valueCaucasians combined / Cases / 1592 / 1490 / 0.9473
Controls / 1727 / 1700 / 0.9533
Caucasians combined
without East Germany / Cases / 1374 / 1273 / 0.9602
Controls / 1513 / 1500 / 0.9598
Hungary / Cases / 245 / 224 / 0.8597
Controls / 78 / 75 / 0.1759
Germany combined / Cases / 1347 / 1266 / 0.9719
Controls / 1649 / 1625 / 0.9993
East Germany / Cases / 218 / 217 / 0.8799
Controls / 212 / 200 / 0.0404
West Germany combined / Cases / 1129 / 1049 / 0.9810
Controls / 1437 / 1425 / 0.8360
W. Germany - ongoing / Cases / 646 / 624 / 0.9995
Controls / 524 / 520 / 0.7833
W. Germany - industrial / Cases / 483 / 425 / 0.8685
Controls / 911 / 905 / 0.9679
DO - hospital / Cases / 111 / 91 / 0.8461
DO - occupational / Cases / 372 / 334 / 0.9613
DO - controls / Controls / 911 / 905 / 0.9679
Non Caucasian study groups
Pakistan / Cases / 101 / 101 / 0.8510
Controls / 226 / 60 / 0.8483
Venezuela / Cases / 112 / 112 / 0.7637
Controls / 190 / 190 / 0.7686
All combined / Cases / 1805 / 1703 / 0.7888
Controls / 2141 / 1950 / 0.9997
All combined
without East Germany / Cases / 1587 / 1486 / 0.8191
Controls / 1929 / 1750 / 0.8410
N*: Number of subjects with complete basis data (age, gender, smoking)
HWE: Hardy-Weinberg equilibrium is tested using the exact chi-square test
Supplemental Table S3. Unadjusted and adjusted analyses for all relevant genetic models indicate a moderate elevated bladder cancer risk for carriers of the frequent [A] allele of rs11892031 consistent with a recessive or intermediate mode of inheritance (supplement to Table 1).
A.Results of the additive and multiplicative mode of inheritance adjusted for age, gender and smoking habits with the [A] allele as risk factor.
Study groups / Status / N / Genotype / Additive model / Multiplicative modelA/A / [A] / P value / OR
95% CI / P value / OR
95% CI
Caucasians combined / Cases / 1490 / 0.88 / 0.94 / 0.1681 / 1.16
0.94-1.44 / 0.1695 / 1.16
0.94-1.44
Controls / 1700 / 0.86 / 0.93
Caucasians combined without East Germany / Cases / 1374 / 0.88 / 0.94 / 0.1780 / 1.17
0.93-1.47 / 0.1812 / 1.17
0.93-1.46
Controls / 1513 / 0.85 / 0.92
Hungary / Cases / 224 / 0.92 / 0.96 / 0.7270 / 1.84
0.75-4.52 / 0.7209 / 1.83
0.74-4.52
Controls / 75 / 0.91 / 0.95
Germany combined / Cases / 1266 / 0.88 / 0.94 / 0.1562 / 1.17
0.94-1.47 / 0.1581 / 1.17
0.94-1.46
Controls / 1625 / 0.86 / 0.93
East Germany / Cases / 217 / 0.93 / 0.96 / 0.6773 / 1.16
0.57-2.35 / 0.6656 / 1.17
0.57-2.43
Controls / 200 / 0.92 / 0.96
West Germany combined / Cases / 1049 / 0.87 / 0.93 / 0.2151 / 1.16
0.92-1.47 / 0.2194 / 1.16
0.92-1.46
Controls / 1425 / 0.85 / 0.92
W. Germany - ongoing / Cases / 624 / 0.85 / 0.92 / 0.7529 / 1.06
0.75-1.48 / 0.7551 / 1.06
0.75-1.48
Controls / 520 / 0.85 / 0.92
W. Germany - industrial / Cases / 425 / 0.89 / 0.94 / 0.0444 / 1.48
1.01-2.17 / 0.0473 / 1.46
1.01-2.13
Controls / 905 / 0.85 / 0.92
DO - hospitala / Cases / 91 / 0.89 / 0.95 / 0.0851 / 1.98
0.91-4.31 / 0.0908 / 1.93
0.90-4.16
DO - occupationala / Cases / 334 / 0.88 / 0.94 / 0.0854 / 1.44
0.95-2.17 / 0.0900 / 1.42
0.95-2.13
DO - controls / Controls / 905 / 0.85 / 0.92
Non Caucasian study groups
Pakistan / Cases / 101 / 0.89 / 0.95 / 0.0341 / 0.33
0.12-0.92 / 0.1427 / 0.34
0.08-1.43
Controls / 60 / 0.92 / 0.96
Venezuela / Cases / 112 / 0.86 / 0.93 / 0.1841 / 1.84
0.75-4.52 / 0.1923 / 1.83
0.74-4.52
Controls / 190 / 0.81 / 0.90
All combined2 / Cases / 1703 / 0.88 / 0.94 / 0.0111 / 1.20
1.04-1.38 / 0.0739 / 1.20
0.98-1.46
Controls / 1950 / 0.86 / 0.93
All combinedwithout East Germany / Cases / 1587 / 0.88 / 0.94 / 0.0883 / 1.20
0.97-1.48 / 0.0913 / 1.20
0.97-1.47
Controls / 1929 / 0.86 / 0.93
aControls are the Dortmund control group (DO-controls)
P values of the Wald test, ORs and 95% CIs for the additive and for the multiplicative ([A] vs. [C]) 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. All study groups combined have been adjusted for different ethnicities.
B.Unadjusted results of the general genetic differences(genotype differences) and recessive mode of inheritance with the [A] allele as risk factor.
Study groups / Status / N / Genotype frequency / Genotypedifferences / Recessive modelA/A / A/C / C/C / P value / OR,
95% CI
A/A vs A/C / OR,
95% CI
A/A vs C/C / P value / OR,
95% CI
Caucasians combined / Cases / 1592 / 0.88 / 0.11 / 0.00 / 0.3251 / 1.12
0.91-1.38 / 1.84
0.62-5.49 / 0.2251 / 1.14
0.92-1.40
Controls / 1725 / 0.86 / 0.13 / 0.01
Caucasians combinedwithout East Germany / Cases / 1374 / 0.88 / 0.12 / 0.004 / 0.4569 / 1.13
0.91-1.41 / 1.43
0.46-4.46 / 0.2349 / 1.14
0.92-1.42
Controls / 1513 / 0.85 / 0.14 / 0.01
Hungary / Cases / 245 / 0.92 / 0.08 / 0.00 / 0.3060 / 1.01
0.39-2.61 / --- / 0.8112 / 1.17
0.40-3.06
Controls / 78 / 0.91 / 0.08 / 0.01
Germany combined / Cases / 1347 / 0.88 / 0.12 / 0.00 / 0.3771 / 1.15
0.92-1.42 / 1.50
0.50-4.48 / 0.1955 / 1.16
0.93-1.44
Controls / 1647 / 0.86 / 0.14 / 0.01
East Germany / Cases / 218 / 0.93 / 0.07 / 0.00 / 0.4927 / 0.97
0.47-2.02 / --- / 0.8572 / 1.10
0.51-2.40
Controls / 212 / 0.92 / 0.07 / 0.01
West Germany combined / Cases / 1129 / 0.87 / 0.13 / 0.00 / 0.5205 / 1.14
0.91-1.43 / 1.12
0.35-3.55 / 0.2572 / 1.14
0.91-1.44
Controls / 1435 / 0.85 / 0.15 / 0.00
W. Germany - ongoing / Cases / 646 / 0.85 / 0.14 / 0.01 / 0.8478 / 1.02
0.74-1.42 / 0.62
0.11-3.38 / 1.0000 / 1.00
0.72-1.40
Controls / 524 / 0.85 / 0.15 / 0.00
W. Germany - industrial / Cases / 483 / 0.89 / 0.11 / 0.00 / 0.1303 / 1.35
0.96-1.89 / 2.76
0.32-23.81 / 0.0608 / 1.38
0.98-1.96
Controls / 911 / 0.85 / 0.14 / 0.01
DO - hospitala / Cases / 111 / 0.89 / 0.11 / 0.00 / 0.3559 / 1.41
0.75-2.63 / --- / 0.2576 / 1.46
0.77-3.00
DO - occupationala / Cases / 372 / 0.88 / 0.11 / 0.00 / 0.2479 / 1.34
0.92-1.93 / 2.12
0.25-18.18 / 0.1111 / 1.35
0.93-2.00
DO - controls / Controls / 911 / 0.85 / 0.14 / 0.01
Non Caucasian study groups
Pakistan / Cases / 101 / 0.89 / 0.11 / 0.00 / 0.5346 / 0.75
0.34-1.64 / --- / 0.5346 / 0.75
0.32-1.82
Controls / 226 / 0.92 / 0.08 / 0.00
Venezuela / Cases / 112 / 0.86 / 0.14 / 0.00 / 0.5414 / 1.41
0.74-2.68 / --- / 0.2765 / 1.45
0.74-2.95
Controls / 190 / 0.81 / 0.19 / 0.01
All combined / Cases / 1805 / 0.88 / 0.12 / 0.003 / 0.1004 / 1.18
0.98-1.43 / 2.03
0.70-5.85 / 0.0571 / 1.20
0.99-1.45
Controls / 2141 / 0.86 / 0.13 / 0.01
All combined
without
East Germany / Cases / 1587 / 0.88 / 0.12 / 0.003 / 0.1596 / 1.19
0.98-1.45 / 1.63
0.54-4.88 / 0.0665 / 1.20
0.99-1.46
Controls / 1929 / 0.86 / 0.14 / 0.005
aControls are the Dortmund control group (DO-controls)
OR: odds ratio; 95% CI: 95% confidence interval
P values of the exact chi-square test, ORs and 95% CIs for the global genotype differences and the recessive model (A/A vs. A/C and C/C) are given.
P values, ORs and 95% CIs for the combined Caucasian groups adjusted for region and 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 with East Germany P=0.9937, without East Germany P= 0.9511; all combined with East Germany P= 0.4169, without East Germany P= 0.4165).
C.Unadjusted results of the additive and multiplicative mode of inheritance with the [A] allele as risk factor.
Study groups / Status / N / Genotype / Additive model / Multiplicative modelA/A / [A] / P value / OR
95% CI / P value / OR
95% CI
Caucasians combined / Cases / 1592 / 0.88 / 0.94 / 0.1750 / 1.15
0.94-1.40 / 0.1752 / 1.15
0.94-1.40
Controls / 1725 / 0.86 / 0.93
Caucasians combinedwithout East Germany / Cases / 1374 / 0.88 / 0.94 / 0.2152 / 1.14
0.93-1.40 / 0.2171 / 1.14
0.93-1.40
Controls / 1513 / 0.85 / 0.92
Hungary / Cases / 245 / 0.92 / 0.96 / 0.6536 / 1.33
0.58-3.05 / 0.6470 / 1.34
0.50-3.28
Controls / 78 / 0.91 / 0.95
Germany combined / Cases / 1347 / 0.88 / 0.94 / 0.1671 / 1.16
0.94-1.42 / 0.1675 / 1.16
0.94-1.42
Controls / 1647 / 0.86 / 0.93
East Germany / Cases / 218 / 0.93 / 0.96 / 0.6209 / 1.21
0.63-2.34 / 0.6065 / 1.23
0.59-2.60
Controls / 212 / 0.92 / 0.96
West Germany combined / Cases / 1129 / 0.87 / 0.93 / 0.2802 / 1.13
0.91-1.40 / 0.2830 / 1.13
0.91-1.40
Controls / 1435 / 0.85 / 0.92
W. Germany - ongoing / Cases / 646 / 0.85 / 0.92 / 0.9380 / 0.99
0.73-1.34 / 0.9384 / 0.99
0.72-1.35
Controls / 524 / 0.85 / 0.92
W. Germany - industrial / Cases / 483 / 0.89 / 0.94 / 0.0515 / 1.38
0.999-1.90 / 0.0528 / 1.37
0.99-1.93
Controls / 911 / 0.85 / 0.92
DO - hospitala / Cases / 111 / 0.89 / 0.95 / 0.2247 / 1.49
0.81-2.73 / 0.2272 / 1.48
0.80-2.98
DO - occupationala / Cases / 372 / 0.88 / 0.94 / 0.1091 / 1.35
0.95-1.92 / 0.1106 / 1.34
0.94- 1.95
DO - controls / Controls / 911 / 0.85 / 0.92
Non Caucasian study groups
Pakistan / Cases / 101 / 0.89 / 0.95 / 0.5346 / 0.75
0.34-1.64 / 0.5444 / 0.76
0.34-1.81
Controls / 226 / 0.92 / 0.96
Venezuela / Cases / 112 / 0.86 / 0.93 / 0.2296 / 1.48
0.79-2.76 / 0.2430 / 1.444
0.76-2.85
Controls / 190 / 0.81 / 0.90
All combined / Cases / 1805 / 0.88 / 0.94 / 0.0407 / 1.21
1.01-1.45 / 0.0411 / 1.21
1.01-1.44
Controls / 2141 / 0.86 / 0.93
All combinedwithout East Germany / Cases / 1587 / 0.88 / 0.94 / 0.0573 / 1.20
0.99-1.45 / 0.0588 / 1.20
0.99-1.44
Controls / 1929 / 0.86 / 0.93
aControls are the Dortmund control group (DO-controls)
Additive model: P values of the exact Cochran-Armitage trend test (2-sided), ORs and 95% CIs are given. The combined Caucasian study groups have been adjusted for different regions, all study groups combined have been adjusted for different ethnicities using logistic regression models.
Multiplicative model ([A] vs. [C]):P values of the exact chi-square test, ORs and 95% CIs are given. P values, ORs and 95% CIs for the combined Caucasian groups adjusted for region and 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 (multiplicative model: Caucasians combined with East Germany P= 0.9060, without East Germany P= 0.6977; all combined with East Germany P= 0.4138, without East Germany P= 0.4179).
Supplemental Table S4. No difference in the distribution of rs11892031 A/A genotypes between ever smokers and non-smokers.
Study groups / Status / Smoking habits / N / Genotype / Global P value(recessive model)
A/A / A/C / C/C
Caucasians combined / Cases / Smokers / 1170 / 0.89 / 0.11 / 0.003 / 0.4527
(0.4230)
Non-smokers / 321 / 0.88 / 0.12 / 0.00
Controls / Smokers / 957 / 0.86 / 0.14 / 0.002 / 0.0729
(0.7442)
Non-smokers / 745 / 0.86 / 0.13 / 0.01
Caucasians combined
without East Germany / Cases / Smokers / 1003 / 0.88 / 0.12 / 0.003 / 0.5426
(0.5690)
Non-smokers / 271 / 0.87 / 0.13 / 0.00
Controls / Smokers / 850 / 0.86 / 0.14 / 0.002 / 0.1994
(0.6865)
Non-smokers / 652 / 0.85 / 0.14 / 0.01
Hungary / Cases / Smokers / 164 / 0.92 / 0.08 / 0.00 / 1.0000
(1.0000)
Non-smokers / 61 / 0.92 / 0.08 / 0.00
Controls / Smokers / 41 / 0.95 / 0.05 / 0.00 / 0.2958
(0.2375)
Non-smokers / 35 / 0.86 / 0.11 / 0.03
Germany combined / Cases / Smokers / 1006 / 0.88 / 0.11 / 0.003 / 0.4139
(0.4554)
Non-smokers / 260 / 0.87 / 0.13 / 0.00
Controls / Smokers / 916 / 0.86 / 0.14 / 0.002 / 0.1085
(1.0000)
Non-smokers / 710 / 0.86 / 0.13 / 0.01
East Germany / Cases / Smokers / 167 / 0.93 / 0.07 / 0.00 / 0.5361
(0.5361)
Non-smokers / 50 / 0.90 / 0.10 / 0.00
Controls / Smokers / 107 / 0.92 / 0.08 / 0.00 / 0.2468
(1.0000)
Non-smokers / 93 / 0.92 / 0.05 / 0.02
West Germany combined / Cases / Smokers / 839 / 0.87 / 0.12 / 0.004 / 0.4901
(0.5673)
Non-smokers / 210 / 0.86 / 0.14 / 0.00
Controls / Smokers / 809 / 0.85 / 0.14 / 0.003 / 0.3782
(0.9405)
Non-smokers / 617 / 0.85 / 0.14 / 0.01
W. Germany - ongoing / Cases / Smokers / 503 / 0.85 / 0.14 / 0.01 / 0.8325
(1.0000)
Non-smokers / 121 / 0.86 / 0.14 / 0.00
Controls / Smokers / 320 / 0.84 / 0.16 / 0.01 / 0.4438
(0.4518)
Non-smokers / 200 / 0.87 / 0.14 / 0.00
W. Germany - industrial / Cases / Smokers / 336 / 0.90 / 0.10 / 0.00 / 0.2540
(0.2540)
Non-smokers / 89 / 0.85 / 0.15 / 0.00
Controls / Smokers / 489 / 0.86 / 0.14 / 0.00 / 0.0450
(0.4555)
Non-smokers / 417 / 0.84 / 0.15 / 0.01
DO - hospital / Cases / Smokers / 75 / 0.92 / 0.08 / 0.00 / 0.6263
(0.6263)
Non-smokers / 16 / 0.88 / 0.13 / 0.00
DO - occupational / Cases / Smokers / 261 / 0.89 / 0.11 / 0.00 / 0.4095
(0.4095)
Non-smokers / 73 / 0.85 / 0.15 / 0.00
DO - controls / Controls / Smokers / 489 / 0.86 / 0.14 / 0.00 / 0.0450
(0.4555)
Non-smokers / 417 / 0.84 / 0.15 / 0.01
Non Caucasian study groups
Pakistan / Cases / Smokers / 67 / 0.90 / 0.10 / 0.00 / 1.0000
(1.0000)
Non-smokers / 34 / 0.88 / 0.11 / 0.00
Controls / Smokers / 51 / 0.96 / 0.04 / 0.00 / 0.3914
(0.3914)
Non-smokers / 9 / 0.89 / 0.11 / 0.00
Venezuela / Cases / Smokers / 99 / 0.87 / 0.13 / 0.00 / 0.3944
(0.3944)
Non-smokers / 13 / 0.77 / 0.23 / 0.00
Controls / Smokers / 71 / 0.80 / 0.18 / 0.01 / 0.5308
(1.0000)
Non-smokers / 119 / 0.81 / 0.19 / 0.00
All combined / Cases / Smokers / 1336 / 0.89 / 0.11 / 0.002 / 0.4145
(0.3922)
Non-smokers / 368 / 0.87 / 0.12 / 0.00
Controls / Smokers / 1079 / 0.86 / 0.13 / 0.003 / 0.1873
(0.7724)
Non-smokers / 873 / 0.85 / 0.14 / 0.01
All combined
without East Germany / Cases / Smokers / 1169 / 0.88 / 0.12 / 0.003 / 0.4879
(0.5000)
Non-smokers / 318 / 0.87 / 0.13 / 0.00
Controls / Smokers / 780 / 0.86 / 0.14 / 0.003 / 0.4302
(0.6819)
Non-smokers / 780 / 0.84 / 0.15 / 0.01
P values of the exact chi-square test for global genotype differences between ever smokers and non smokers are given (global P value). P values of the exact chi-square test for a different A/A distribution between ever smokers and non-smokers are given in parenthesis (recessive model). 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 homogeneity of the ORs in the combined study groups (Caucasian cases combined P=0.8433, without East Germany P= 0.8729; Caucasian controls combined P=0.3752, without East Germany P=0.1737; all cases combined P= 0.7479, without East Germany P= 0.7237; all controls combined P=0.6703; without East Germany P=0.6735).
Supplemental Table S5. No association between rs11892031 and urinary bladder cancer carcinogens.
A. No difference in the distribution of rs11892031between individuals exposed and non exposed to urinary bladder carcinogens.
Exposure / Study groups / Status / Exposure / N / Genotype / Allele [A] / Global P value(recessive model)
A/A / A/C / C/C
PAH / All combined / Cases / exposed / 77 / 0.86 / 0.14 / 0.00 / 0.93 / 0.3453
not exposed / 319 / 0.91 / 0.09 / 0.00 / 0.95 / (0.3453)
East Germany / Cases / exposed / 18 / 0.89 / 0.11 / 0.00 / 0.94 / 1.0000
not exposed / 174 / 0.92 / 0.08 / 0.00 / 0.96 / (1.0000)
Controls / exposed / 2 / 1.00 / 0.00 / 0.00 / 1.00 / 1.0000
not exposed / 197 / 0.92 / 0.07 / 0.01 / 0.95 / (1.0000)
DO - occupational / Cases / exposed / 59 / 0.85 / 0.15 / 0.00 / 0.92 / 0.4803
not exposed / 145 / 0.89 / 0.11 / 0.00 / 0.94 / (0.4803)
AA / All combined / Cases / exposed / 143 / 0.90 / 0.10 / 0.00 / 0.95 / 0.4130
not exposed / 341 / 0.90 / 0.10 / 0.00 / 0.95 / (0.4130)
East Germany / Cases / exposed / 13 / 1.00 / 0.00 / 0.00 / 1.00 / 0.3926
not exposed / 180 / 0.91 / 0.09 / 0.00 / 0.96 / (0.3926)
Controls / exposed / 2 / 1.00 / 0.00 / 0.00 / 1.00 / 1.0000
not exposed / 197 / 0.92 / 0.07 / 0.01 / 0.95 / (1.0000)
DO - occupational / Cases / exposed / 130 / 0.88 / 0.12 / 0.00 / 0.94 / 0.8247
not exposed / 74 / 0.86 / 0.14 / 0.00 / 0.93 / (0.8247)
DO - hospital / Cases / exposed / 0 / --- / --- / --- / --- / ---
not exposed / 87 / 0.92 / 0.08 / 0.00 / 0.96
AD / All combined / Cases / exposed / 174 / 0.89 / 0.11 / 0.00 / 0.94 / 0.8638
not exposed / 318 / 0.91 / 0.09 / 0.00 / 0.96 / (0.8638)
East Germany / Cases / exposed / 35 / 0.94 / 0.06 / 0.00 / 0.97 / 0.7433
not exposed / 166 / 0.92 / 0.08 / 0.00 / 0.96 / (0.7433)
Controls / exposed / 22 / 0.86 / 0.14 / 0.00 / 0.93 / 0.5058
not exposed / 176 / 0.93 / 0.06 / 0.01 / 0.96 / (0.3955)
DO - occupational / Cases / exposed / 132 / 0.87 / 0.13 / 0.00 / 0.94 / 0.8250
not exposed / 72 / 0.89 / 0.11 / 0.00 / 0.94 / (0.8250)
DO - hospital / Cases / exposed / 7 / 0.86 / 0.14 / 0.00 / 0.93 / 1.0000
not exposed / 80 / 0.93 / 0.08 / 0.00 / 0.96 / (1.0000)
PAH or AA / All combined / Cases / exposed / 189 / 0.89 / 0.11 / 0.00 / 0.95 / 0.4209
not exposed / 207 / 0.90 / 0.10 / 0.00 / 0.95 / (0.4209)
East Germany / Cases / exposed / 31 / 0.94 / 0.06 / 0.00 / 0.97 / 0.7500
not exposed / 161 / 0.91 / 0.09 / 0.00 / 0.96 / (0.7500)
Controls / exposed / 2 / 1.00 / 0.00 / 0.00 / 1.00 / 1.0000
not exposed / 197 / 0.92 / 0.07 / 0.01 / 0.95 / (1.0000)
DO - occupational / Cases / exposed / 158 / 0.89 / 0.11 / 0.00 / 0.94 / 0.6092
not exposed / 46 / 0.85 / 0.15 / 0.00 / 0.92 / (0.6092)
PAH, AA or AD / All combined / Cases / exposed / 244 / 0.89 / 0.06 / 0.00 / 0.92 / 0.4949
not exposed / 150 / 0.90 / 0.10 / 0.00 / 0.95 / (0.4949)
East Germany / Cases / exposed / 61 / 0.93 / 0.07 / 0.00 / 0.97 / 0.5906
not exposed / 129 / 0.91 / 0.09 / 0.00 / 0.95 / (0.5906)
Controls / exposed / 23 / 0.87 / 0.13 / 0.00 / 0.93 / 0.5169
not exposed / 174 / 0.93 / 0.06 / 0.01 / 0.96 / (0.4078)
DO- occupational / Cases / exposed / 183 / 0.88 / 0.12 / 0.00 / 0.94 / 1.0000
not exposed / 21 / 0.86 / 0.14 / 0.00 / 0.93 / (1.0000)
PAH or ever smoking / All combined / Cases / exposed / 447 / 0.90 / 0.10 / 0.00 / 0.95 / 0.7520
not exposed / 69 / 0.90 / 0.10 / 0.00 / 0.95 / (0.7520)
East Germany / Cases / exposed / 173 / 0.92 / 0.08 / 0.00 / 0.96 / 1.0000
not exposed / 39 / 0.92 / 0.08 / 0.00 / 0.96 / (1.0000)
Controls / exposed / 107 / 0.92 / 0.08 / 0.00 / 0.96 / 0.2468
not exposed / 93 / 0.92 / 0.05 / 0.02 / 0.95 / (1.0000)
DO- occupational / Cases / exposed / 274 / 0.89 / 0.11 / 0.00 / 0.95 / 0.7585
not exposed / 30 / 0.87 / 0.13 / 0.00 / 0.93 / (0.7585)
PAH, AA or ever smoking / All combined / Cases / exposed / 465 / 0.91 / 0.09 / 0.00 / 0.95 / 0.1563
not exposed / 51 / 0.86 / 0.14 / 0.00 / 0.93 / (0.1563)
East Germany / Cases / exposed / 175 / 0.93 / 0.02 / 0.00 / 0.93 / 1.0000
not exposed / 37 / 0.92 / 0.08 / 0.00 / 0.96 / (1.0000)
Controls / exposed / 107 / 0.92 / 0.08 / 0.00 / 0.96 / 0.2468
not exposed / 93 / 0.92 / 0.05 / 0.02 / 0.95 / (1.0000)
DO- occupational / Cases / exposed / 290 / 0.90 / 0.10 / 0.00 / 0.95 / 0.0581
not exposed / 14 / 0.71 / 0.29 / 0.00 / 0.86 / (0.0581)
PAH, AA, AD or ever smoking / All combined / Cases / exposed / 476 / 0.90 / 0.10 / 0.00 / 0.95 / 0.8662
not exposed / 40 / 0.93 / 0.08 / 0.00 / 0.96 / (0.8662)
East Germany / Cases / exposed / 179 / 0.92 / 0.08 / 0.00 / 0.96 / 1.0000
not exposed / 33 / 0.94 / 0.06 / 0.00 / 0.97 / (1.0000)
Controls / exposed / 118 / 0.91 / 0.09 / 0.00 / 0.95 / 0.0546
not exposed / 82 / 0.94 / 0.04 / 0.02 / 0.96 / (0.4432)
DO- occupational / Cases / exposed / 297 / 0.89 / 0.11 / 0.00 / 0.94 / 1.0000
not exposed / 7 / 0.86 / 0.14 / 0.00 / 0.93 / (1.0000)
PAH polycyclic aromatic hydrocarbons. AA aromatic amines. AD azo dyes
All combined comprises the case groups from East Germany, W. Germany - occupational and W. Germany - hospital.
P values of the exact chi-square test for global genotype differences (global P value) 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) are given in parenthesis. P values for combined case groups were calculated using the method of Mantel-Haenszel. All combined study groups were homogenous as checked by the Breslow-Day test.
B. No differences between cases and controls in the subgroups of exposed and not exposed persons.
Exposure / Study groups / Exposure / Status / N / Frequency / Global P value / Recessive modelP value
A/A / [A]
PAH / All combined
(East Germany, DO– occupational) / exposed / Cases / 77 / 0.86 / 0.93 / - / -
Controls / 2 / 1.0 / 1.00
not exposed / Cases / 319 / 0.91 / 0.95 / 0.1259 / 0.6384
Controls / 197 / 0.92 / 0.95
East Germany / exposed / Cases / 18 / 0.89 / 0.94 / - / -
Controls / 2 / 1.0 / 1.0
not exposed / Cases / 174 / 0.92 / 0.96 / 0.5405 / 1.0000
Controls / 197 / 0.92 / 0.95
AA / All combined
(East Germany, DO – occupational, DO– hospital) / exposed / Cases / 143 / 0.90 / 0.95 / - / -
Controls / 2 / 1.0 / 1.0
not exposed / Cases / 341 / 0.90 / 0.95 / 0.0970 / 0.6415
Controls / 197 / 0.92 / 0.95
East Germany / exposed / Cases / 13 / 1.0 / 1.0 / - / -
Controls / 2 / 1.0 / 1.0
not exposed / Cases / 180 / 0.91 / 0.96 / 0.4469 / 0.7898
Controls / 197 / 0.92 / 0.95
AD / All combined
(East Germany, DO– occupational, DO– hospital) / exposed / Cases / 174 / 0.89 / 0.94 / 1.0000 / 1.0000
Controls / 22 / 0.86 / 0.93
not exposed / Cases / 318 / 0.91 / 0.96 / 0.0882 / 0.6149
Controls / 176 / 0.93 / 0.96
East Germany / exposed / Cases / 35 / 0.94 / 0.97 / 0.3638 / 0.3638
Controls / 22 / 0.86 / 0.93
not exposed / Cases / 166 / 0.92 / 0.96 / 0.3393 / 0.8415
Controls / 176 / 0.93 / 0.96
PAH or AA / All combined
(East Germany, DO– occupational) / exposed / Cases / 189 / 0.89 / 0.95 / - / -
Controls / 2 / 1.0 / 1.0
not exposed / Cases / 207 / 0.90 / 0.95 / 0.1710 / 0.4961
Controls / 197 / 0.92 / 0.95
East Germany / exposed / Cases / 31 / 0.94 / 0.97 / - / -
Controls / 2 / 1.0 / 1.0
not exposed / Cases / 161 / 0.91 / 0.96 / 0.4960 / 0.8505
Controls / 197 / 0.92 / 0.95
PAH, AA or AD / All combined
(East Germany DO– occupational) / exposed / Cases / 244 / 0.89 / 0.95 / 0.7246 / 0.7246
Controls / 23 / 0.87 / 0.93
not exposed / Cases / 150 / 0.90 / 0.95 / 0.1845 / 0.4351
Controls / 174 / 0.93 / 0.96
East Germany / exposed / Cases / 61 / 0.93 / 0.97 / 0.3857 / 0.3857
Controls / 23 / 0.87 / 0.93
not exposed / Cases / 129 / 0.91 / 0.95 / 0.3684 / 0.6737
Controls / 174 / 0.93 / 0.96
PAH or ever smoking / All combined
(East Germany, DO– occupational) / exposed / Cases / 447 / 0.90 / 0.95 / 0.7206 / 0.7206
Controls / 107 / 0.92 / 0.96
not exposed / Cases / 69 / 0.90 / 0.95 / 0.3619 / 0.5828
Controls / 93 / 0.92 / 0.95
East Germany / exposed / Cases / 173 / 0.92 / 0.96 / 0.8214 / 0.8214
Controls / 107 / 0.92 / 0.96
not exposed / Cases / 39 / 0.92 / 0.96 / 0.6129 / 1.0000
Controls / 93 / 0.92 / 0.95
PAH, AA or ever smoking / All combined
(East Germany, DO– occupational) / exposed / Cases / 465 / 0.91 / 0.95 / 0.8547 / 0.8547
Controls / 107 / 0.92 / 0.96
not exposed / Cases / 51 / 0.86 / 0.93 / 0.1680 / 0.2502
Controls / 93 / 0.92 / 0.95
East Germany / exposed / Cases / 175 / 0.93 / 0.96 / 0.8206 / 0.8206
Controls / 107 / 0.92 / 0.96
not exposed / Cases / 37 / 0.92 / 0.96 / 0.6118 / 1.0000
Controls / 93 / 0.92 / 0.95
PAH, AA, AD or ever smoking / All combined
(East Germany, DO– occupational) / exposed / Cases / 476 / 0.90 / 0.95 / 0.8665 / 0.8665
Controls / 118 / 0.91 / 0.95
not exposed / Cases / 40 / 0.93 / 0.96 / 0.4816 / 1.0000
Controls / 82 / 0.94 / 0.96
East Germany / exposed / Cases / 179 / 0.92 / 0.96 / 0.6734 / 0.6734
Controls / 118 / 0.91 / 0.95
not exposed / Cases / 33 / 0.94 / 0.97 / 0.5306 / 1.0000
Controls / 82 / 0.94 / 0.96
PAH polycyclic aromatic hydrocarbons. AA aromatic amines. AD azo dyes
All combined comprises the case groups from East Germany, DO- occupational and DO- hospital
P values of the exact chi-square test for global genotype differences (global P value) and for the recessive model (A/A vs. A/C and C/C) between cases and controls
Supplemental Figures S1-S2
Supplemental Figure S1. Composition of the study groups collected by the Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany, and cooperation partners
Abbreviations of the study groups are printed in Italic, the number of cases and controls are given in parenthesis (cases/controls).
Supplemental Figure S2. Funnel-Plot of the ORs and standard errors of the individual case-control series included in the meta-analysis indicates no systematic bias
The dots represent the ORs and standard errors of each individual case-control-series that was included in the meta-analysis (Figure 2). Egger’s test confirms that there is no obvious bias in the data (P=0.8954).