Baseline characteristics
In total 67 potentially eligible studies from 156 retrieved articles were identified (Fig. 1). Thirty-eight investigators agreed to participate and 24 [10–34] provided data (Table 1). Reasons for non-participation after initially agreement were: no data on diet or the minimum set of confounders available, the workload that was already too high and the wish to publish the results on nutrition first before participating in a pooled study. With some investigators, we lost communication after initial contact. The first datasets and codebooks were collected in March 2009 while the last dataset was included in March 2016. Another two new studies, one case–control and one cohort study are available for inclusion.
Flow diagram of the Bladder cancer Epidemiology and Nutritional Determinants study (BLEND)
Characteristics of the studies included in the pooled analysis of the Bladder cancer Epidemiology and Nutritional Determinants study (BLEND)
Study
Country
Recruitment
period
Study design
Cases
N
Controls
N
men
women
total
men
women
total
Case–control studies
?Los-Angeles bladder cancer Case–control study [10]
USA
1987–1999
Population based case–control
1,307
353
1,660
1,237
349
1,586
?Roswell Park Cancer Institute [11]
USA
1982–1998
Hospital-based case–control
164
53
217
501
163
664
?Belgian Case–control study on bladder cancer [12]
Belgium
1999–2004
Population based case–control
172
28
200
228
156
384
?Aichi Prefecture Case–control study [13]
Japan
1996–1999
Hospital-based case–control
245
58
303
244
59
303
?Kaohsiung [14]
Taiwan
1996–1997
Hospital-based case–control
31
9
40
124
36
160
?Hessen Case–control study on bladder cancer [15]
Germany
1989–1992
Hospital-based case–control
239
61
300
239
61
300
?Stockholm Case–control study [16]
Sweden
1985–1987
Population based case–control
204
67
271
281
268
549
?Roswell Park Memorial Institute Case–control study on bladder cancer [17]
USA
1957–1965
Hospital-based case–control
415
138
553
3,253
4,636
7,889
?Reina Sofia University Hospital [18]
Spain
1997
Hospital-based case–control
74
11
85
89
41
130
?New Hampshire bladder cancer study [19]
USA
1994–2001
Population based case–control
286
104
390
185
138
323
?Italian Case–control study on bladder cancer [20]
Italy
1985–1993
Hospital-based case–control
617
110
727
766
298
1,064
?Brescia bladder cancer study [21]
Italy
1997–2000
Hospital-based case–control
200
0
200
214
0
214
?Dortmund Hörde study [22]
Germany
2009–2010
Hospital based case–control
145
48
193
177
56
233
?National Enhanced Cancer Surveillance System (NESCC) [23]
Canada
1994–1997
Population based case–control
600
311
911
2,451
2,423
4,874
?French INSERM study [24]
France
1984–1987
Hospital-based case–control
166
33
199
275
47
322
?South and East China Case–control study on bladder and prostate cancer [25]
China
2005–2008
Hospital-based case–control
390
93
483
364
100
464
?Molecular Epidemiology of Bladder Cancer and Prostate Cancer [26]
USA
1993–1997
Hospital-based case–control
149
45
194
243
58
301
?North Carolina case control study [27]
USA
1987–1991
Hospital-based case–control
188
56
244
174
41
215
Cohort studies
?Swedish Mammography Cohort (SMC) the Cohort of Swedish Men [28]
Sweden
1987–1990
Population based cohort
538
119
657
2,188
484
2,672
?Netherlands Cohort Study on diet and cancer [29]
The Netherlands
1986–2003
Population based cohort
779
161
940
2,273
2,419
4,692
?Women’s Lifestyle and Health Study [30]
Norway, Sweden
1991–2006
Population based cohort
0
49
49
0
48,942
48,942
?RERF atomic bomb survivors Study [31]
Japan
1950–2000
Population based cohort
216
85
301
19,362
28,249
47,611
?VITamins and Lifestyle Study (VITAL) [32]
USA
2000–2008
Population based cohort
338
106
444
36,454
39,983
76,437
?European Prospective Investigation into Cancer and Nutrition (EPIC) [33, 34]
Europe
1993–2006
Population based cohort
1,227
525
1,752
141,872
333,279
475,151
TOTAL
–
–
–
8,657
2,604
11,313
213,227
462,305
675,480
More than 2/3 of the case–control studies [11, 13–15, 17, 18, 20–22, 24–27] had a hospital-based case–control design. Ten studies [12, 16, 19–21, 24–28] were also part of the International Bladder Cancer Consortium that was formed in 2005 as an open scientific forum for genetic-epidemiologic researchers in the field of UBC. Most of the studies [12, 15, 16, 18, 20–22, 24, 28–30, 33, 34] were from Europe, eight studies [10, 11, 17, 19, 23, 26, 27, 32] were from the USA and Canada, and four [13, 14, 25, 31] studies were from Asia.
After excluding participants with unknown age (n?=?5), unknown case–control status (n?=?214) and unknown smoking status (n?=?14,028) data of 686,793 participants were available for analyses of which 11,261 cases and 675,532 non-cases. The Brescia bladder cancer study [21] contained only male participants, while the Women’s Lifestyle and Health study consisted of only female participants. Most of the cases were from America to Europe while only 10 % were from Asia.
The cases of the European and Asian case–control studies had the highest male/female ratio (4:1) while their overall male/female ratio was 3:1 (Table 2). In general, controls were younger than cases, 57.0 versus 61.6 years and 51.8 versus 61.1 years, respectively for case–control studies and cohort studies with an exception for the Asian case–control studies (66.1 versus 64.9 years). Most of the participants were Caucasian, whereas only 10 % of the cases were Asian. In contrast with Asia, where one third of the cases were never smoker, only one fifth of the cases never smoked in Europe and USA. Overall, 40 % of the cases were smokers. Controls had significant less current and more never smokers than cases. For cohort studies, nearly half of the controls never smoked. Staging was not reported in 60 and 70 % respectively for the case–control and cohort studies.
Characteristics of the study population of the Bladder cancer Epidemiology and Nutritional Determinants study (BLEND)
Total
Europe
America
Asia
Cases
Controls
Cases
Controls
Cases
Controls
Cases
Controls
N
(()
N
(%)
N
(%)
N
(%)
N
(%)
N
(%)
N
(%)
N
(%)
Case–control studies
Gender
?Male
5,592
(77.9)
11,045
(55.9)
1,817
(83.5)
2,269
(71.0)
3,109
(74.6)
8,044
(50.7)
666
(80.6)
732
(79.0)
?Female
1,578
(22.1)
8,930
(44.1)
358
(16.5)
927
(29.0)
1,060
(25.4)
7,808
(49.3)
160
(19.4)
195
(21.0)
?
Age (mean, SD)
61.6
(11.4)
57.0
(14.4)
65.4
(9.7)
63.3
(10.9)
59.0
(11.1)
55.3
(14.5)
64.9
(13.1)
66.1
(12.2)
???50
961
(13.4)
5,665
(28.4)
135
(6.2)
308
(9.6)
723
(17.3)
5,271
(33.3)
103
(12.5)
86
(9.3)
?50–?59
1,832
(25.6)
4,501
(22.5)
407
(18.7)
787
(24.6)
1,261
(30.2)
3,549
(22.4)
164
(19.9)
165
(17.8)
?60–64
1,399
(19.5)
2,772
(13.9)
381
(17.5)
555
(17.4)
929
(22.3)
2,1
(13.2)
89
(10.8)
117
(12.6)
?65–69
1,122
(15.6)
2,842
(14.2)
482
(22.2)
567
(17.7)
522
(12.5)
2,138
(13.5)
118
(14.3)
137
(14.8)
????70
1,856
(25.9)
4,195
(21.0)
770
(35.4)
979
(30.6)
734
(17.6)
2,794
(17.6)
352
(42.6)
422
(45.5)
Ethnic group
?Caucasian
4,438
(61.9)
15,057
(75.4)
593
(27.3)
831
(26.0)
3,845
(92.2)
14,226
(89.2)
782
(94.7)
767
(82.7)
?Mixed
9
(0.1)
10
(0.1)
–
–
–
–
9
(0.2)
10
(0.1)
–
–
–
–
?Asian
788
(11.0)
895
(4.5)
–
–
–
–
6
(0.1)
128
(0.8)
–
–
–
–
?Black
52
(0.7)
748
(3.7)
–
–
–
–
52
(1.2)
748
(4.7)
–
–
–
–
?Any other ethnic group
64
(0.9)
232
(1.2)
–
–
–
–
21
(0.5)
72
(0.5)
43
(5.2)
160
(17.3)
?Unknown
1,819
(25.4)
3,033
(15.2)
1,582
(72.7)
2,365
(74.0)
236
(5.7)
668
(4.2)
1
(0.1)
–
–
Tobacco smoking status
?Current smoker
2,95
(41.1)
6,98
(34.9)
1,038
(47.7)
1,022
(32.0)
1,564
(37.5)
5,695
(35.9)
348
(42.1)
263
(28.4)
?Former smoker
2,703
(37.7)
5,269
(26.4)
747
(34.3)
1,025
(32.1)
1,731
(41.5)
3,943
(24.9)
225
(27.2)
301
(32.5)
?Never smoker
1,517
(21.2)
7,726
(38.7)
390
(17.9)
1,149
(36.0)
874
(21.0)
6,214
(39.2)
253
(30.6)
363
(39.2)
Staging
?Non–invasive
2,246
(31.3)
–
–
511
(23.5)
–
–
1,606
(38.5)
–
–
129
(15.6)
–
–
?Invasive
609
(8.5)
–
–
73
(3.4)
–
–
366
(8.8)
–
–
170
(20.6)
–
–
?Unknown
4,315
(60.2)
–
–
1,591
(73.1)
–
–
2,197
(52.7)
–
–
527
(63.8)
–
–
Continent
?Europe
2,175
(30.3)
3,196
(16.0)
–
–
–
–
–
–
–
–
–
–
–
–
?America
4,169
(58.1)
15,852
(79.4)
–
–
–
–
–
–
–
–
–
–
–
–
?Asia
826
(11.5)
927
(4.6)
–
–
–
–
–
–
–
–
–
–
–
–
Cohort studies
Gender
?Male
2,866
(69.2)
205,678
(31.4)
2,544
(74.9)
146,333
(27.5)
338
(76.1)
39,983
(52.3)
216
(71.8)
19,362
(40.7)
?Female
1,277
(30.8)
449,827
(68.6)
854
(25.1)
385,124
(72.5)
106
(23.9)
36,454
(47.7)
85
(28.2)
28,249
(59.3)
?
Age (mean, SD)
61.1
(8.5)
51.8
(10.8)
60.9
(7.9)
50.4
(10.2)
66.4
(6.4)
61.4
(7.4)
55.7
(12.0)
52.0
(13.6)
???50
380
(9.2)
270,949
(41.3)
277
(8.2)
249,151
(46.9)
–
–
–
–
103
(34.2)
21,798
(45.8)
?50–59
1,305
(31.5)
232,316
(35.4)
1,154
(34.0)
184,999
(34.8)
69
(15.5)
35,193
(46.0)
82
(27.2)
12,124
(25.5)
?60–64
1,114
(26.9)
81,842
(12.5)
974
(28.7)
62,868
(11.8)
92
(20.7)
13,923
(18.2)
48
(15.9)
5,051
(10.6)
?65–69
757
(18.3)
39,082
(6.0)
610
(18.0)
22,425
(4.2)
109
(24.5)
12,561
(16.4)
38
(12.6)
4,096
(8.6)
????70
587
(14.2)
31,316
(4.8)
383
(11.3)
12,014
(2.3)
174
(39.2)
14,760
(19.3)
30
(10.0)
4,542
(9.5)
Ethnic group
?Caucasian
3,815
(92.1)
602,416
(91.9)
3,398
(100)
531,457
(100)
417
(93.9)
70,959
(92.8)
–
–
–
–
?Asian
314
(7.6)
50,651
(7.7)
–
–
–
–
13
(2.9)
3,04
(4.0)
301
(100)
47,611
(100)
?Black
7
(0.2)
969
(0.1)
–
–
–
–
7
(1.6)
969
1.3)
–
–
–
–
?Any other ethnic group
1
(0.0)
475
(0.1)
–
–
–
–
1
(0.2)
475
(0.6)
–
–
–
–
?Unknown
6
(0.1)
994
(0.2)
–
–
–
–
6
(1.4)
994
(1.3)
–
–
–
–
Tobacco smoking status
?Current smoker
1,677
(40.5)
156,467
(23.9)
1,418
(41.7)
130,871
(24.6)
61
(13.7)
6,411
(8.4)
198
(65.8)
19,185
(40.3)
?Former smoker
1,594
(38.5)
185,006
(28.2)
1,296
(38.1)
149,472
(28.1)
280
(63.1)
33,651
(44.0)
18
(6.0)
1,883
(4.0)
?Never smoker
872
(21.0)
314,032
(47.9)
684
(20.1)
251,114
(47.3)
103
(23.2)
36,375
47.6)
85
(28.2)
26,543
(55.7)
Staging
?Non–invasive
1,196
(28.9)
–
–
1,196
(35.2)
–
–
–
–
–
–
–
–
–
–
?Invasive
661
(16.0)
–
–
661
(19.5)
–
–
–
–
–
–
–
–
–
–
?Unknown
2,286
(55.2)
–
–
1,541
(45.4)
–
–
444
(100)
–
–
301
(100)
–
–
Continent
?Europe
3,398
(82.0)
531,457
(81.1)
–
–
–
–
–
–
–
–
–
–
–
–
?America
444
(10.7)
76,437
(11.7)
–
–
–
–
–
–
–
–
–
–
–
–
?Asia
301
(7.3)
47,611
(7.3)
–
–
–
–
–
–
–
–
–
–
–
–
Although all of the studies used a food frequency questionnaire (FFQ), the number of food items assessed varied widely (Table 3). Two studies [22, 24] only asked three and two specific items (beer, coffee and decaffeinated coffee), while others assessed dietary intake in more detail (from 9 [27] to 788 food items [12]). The mean number of food items per questionnaire was 107 and 132 after exclusion of those studies that reported only on beverages [14, 22, 24]. Most studies with a FFQ of more than 40 items had detailed information on dietary intake of meat, vegetables, fruit and beverages. The use of a validated FFQ questionnaire was reported in eight studies [12, 19, 23, 28–30, 32–34], while one study checked the reproducibility of its FFQ [20]. Most of the studies assessed portion size, while four studies [12, 28, 29, 33, 34] reported the quantitative intake of food items in grams. Six studies [10, 19, 28, 30, 32–34] also provided data on nutrients.
Number of food items and portion size reported by each study within the Bladder cancer Epidemiology and Nutritional Determinants study (BLEND)
aDietary intake was assessed by a number of different instruments in the participating countries and the number of different food items varied from 88 (Norway) to 2443 (Sweden)
The consumption of beverages was reported in all the eighteen case–control studies. Five case–control studies [12, 13, 16, 19, 26] had detailed information for each of the larger food categories of the Eurocode 2 Food Coding System, while three studies [11, 23, 25] missed only data on sugar and/or fat (Table 4). Fat, grains, nuts and sugar were also missing in another four studies [10, 15, 17, 20]. The six cohort studies [28–34] had detailed information in each food categories with the exception of the RERF atomic bomb survivors study [31] which had no data on sugar intake.
Numbers of cases and controls available for each food category included in the Bladder cancer Epidemiology and Nutritional Determinants study (BLEND)
All Countries
Europe
America
Asia
Men
Women
Men
Women
Men
Women
Men
Women
Food category (number of studies)
Ca
N
Co
N
Ca
N
Co
N
Ca
N
Co
N
Ca
N
Co
N
Ca
N
Co
N
Ca
N
Co
N
Ca
N
Co
N
Ca
N
Co
N
Case–control studies
Milk and milk products (13) [10–17, 19, 20, 23, 25, 26]
4,734
9,251
1,388
7,442
1,231
1,514
266
783
2,838
7,005
962
6,464
665
732
160
195
Eggs and eggs products (11) [10–13, 15, 16, 19, 20, 23, 25, 26]
4,299
6,531
1,255
3,974
1,230
1,512
265
781
2,436
4,141
839
3,034
633
605
151
159
Meat and meat products (12) [10–13, 15–17, 19, 20, 23, 25, 26]
4,699
9235
1,377
7,716
1,231
1,513
265
783
2,833
7,114
961
6,774
635
608
151
159
Fish and fish products (11) [11–13, 15–17, 19, 20, 23, 25, 26]
3,197
7,391
960
7,144
1,229
1,511
265
781
1,335
5,275
544
6,204
633
605
151
159
Fats and oils (7) [10–13, 16, 19, 26]
2,299
2,292
634
984
371
500
94
419
1,689
1,559
484
506
239
233
56
59
Grain and grain products (11) [10–13, 16, 17, 19, 21, 23, 25, 26]
4,050
8,481
1,209
7,404
574
721
94
424
2,841
7,153
964
6,821
635
607
151
159
Pulses, seeds and nut products (8) [11–13, 16, 19, 23, 25, 26]
2,108
4,255
715
3,270
371
499
94
421
1,106
3,151
470
2,690
631
605
151
159
Vegetables (13) [10–13, 15–17, 19–21, 23, 25, 26]
4,942
10,086
1,403
8,648
1,429
1,727
265
783
2,881
7,754
987
7,706
632
605
151
159
Fruit and fruit products (13) [10–13, 15–17, 19–21, 23, 25, 26]
4,860
9,307
1,376
7,615
1,414
1,713
265
781
2,814
6,989
960
6,675
632
605
151
159
Sugar products (7) [12, 13, 16, 18, 19, 23, 26]
1,613
3,438
582
3,020
446
591
105
463
935
2,615
421
2,499
232
232
56
58
Beverages (18) [10–27]
5,509
10193
1,538
7,640
1,814
2,269
357
926
3,030
7,192
1,021
6,519
665
732
160
195
Cohort studies
Milk and milk products (6) [28–34]
2,615
184,424
1,159
422,716
2,495
146,183
835
384,864
86
35,753
314
33,742
34
2,488
10
4,110
Eggs and eggs products (6) [28–34]
2,585
184,284
1,147
421,392
2,465
146,039
823
383,535
86
35,753
314
33,742
34
2,492
10
4,115
Meat and meat products (6) [28–34]
2,614
184,420
1,156
422,122
2,494
146,171
832
384,262
86
35,753
314
33,742
34
2,496
10
4,118
Fish and fish products (6) [28–34]
2,613
184,406
1,157
421,976
2,493
146,157
833
384,116
86
35,753
314
33,742
34
2,496
10
4,118
Fats and oils (6) [28–34]
2,527
181,544
1,130
421,335
2,420
146,029
810
384,710
86
35,753
314
33,742
21
1,762
6
2,883
Grain and grain products (6) [28–34]
2,618
184,446
1,158
422,738
2,498
146,194
834
384,876
86
35,753
314
33,742
34
24,99
10
4,120
Pulses, seeds and nut products (6) [28–34]
2,563
184,228
1,143
420,368
2,443
145,984
819
382,512
86
35,753
314
33,742
34
2,491
10
4,114
Vegetables (6) [28–34]
2,616
184,432
1,157
422,236
2,496
146,184
833
384,376
86
35,753
314
33,742
34
2495
10
4118
Fruit and fruit products (6) [28–34]
2,607
184,416
1,155
421,526
2,487
146,170
831
383,666
86
35,753
314
33,742
34
2493
10
4118
Sugar products (5) [28–30, 32–34]
2,556
181,860
1,143
417,615
2,470
146,107
829
383,873
86
35,753
314
33,742
0
0
0
0
Beverages (6) [28–34]
2,630
187,445
1,172
424,778
2,497
146,190
835
384,868
99
38,760
327
35,793
34
2495
10
4117
Abbreviations: Ca cases, Co controls, N number