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. 2014 Aug 14;111(9):1870–1880. doi: 10.1038/bjc.2014.459

Table 4. HRs and 95% CIs for bladder cancer, by quintiles of flavonoids in the EPIC study.

    Bladder cancer
UCC
Aggressive UCC
Non-aggressive UCC
    No of cases Crude Multivariable No of cases Crude Multivariable No of cases Crude Multivariable No of cases Crude Multivariable
  Intake   HR (95% CI) HR (95% CI)   HR (95% CI) HR (95% CI)   HR (95% CI) HR (95% CI)   HR (95% CI) HR (95% CI)
Total flavonoids
Quintile 1 <175.8 354 1 (ref) 1 (ref) 325 1 (ref) 1 (ref) 109 1 (ref) 1 (ref) 81 1 (ref) 1 (ref)
Quintile 2 175.8–275.8 326 0.91 (0.78–1.06) 1.01 (0.87–1.18) 293 0.92 (0.78–1.07) 1.02 (0.87–1.20) 91 0.87 (0.66–1.16) 0.98 (0.73–1.30) 77 1.00 (0.73–1.38) 1.16 (0.84–1.59)
Quintile 3 275.9–404.8 288 0.83 (0.70–0.98) 0.96 (0.81–1.14) 256 0.84 (0.71–0.99) 0.97 (0.82–1.16) 78 0.80 (0.59–1.09) 0.94 (0.69–1.28) 78 1.04 (0.75–1.44) 1.27 (0.91–1.77)
Quintile 4 404.9–658.4 289 0.75 (0.64–0.89) 0.91 (0.76–1.08) 259 0.77 (0.65–0.92) 0.93 (0.77–1.12) 72 0.71 (0.52–0.98) 0.86 (0.62–1.20) 86 1.00 (0.72–1.40) 1.30 (0.92–1.83)
Quintile 5 >658.4 318 0.75 (0.62–0.90) 0.91 (0.75–1.10) 292 0.75 (0.62–0.91) 0.92 (0.75–1.12) 80 0.69 (0.49–0.98) 0.86 (0.60–1.23) 91 0.95 (0.66–1.35) 1.26 (0.87–1.83)
P-trend     0.002 0.23   0.004 0.30   0.039 0.36   0.69 0.34
Continuous (log2)     0.91 (0.86–0.95) 0.97 (0.92–1.03)   0.91 (0.86–0.96) 0.97 (0.92–1.03)   0.89 (0.81–0.99) 0.96 (0.87–1.07)   0.98 (0.88–1.09) 1.08 (0.97–1.20)
Flavanols
Quintile 1 <122.3 345 1 (ref) 1 (ref) 318 1 (ref) 1 (ref) 104 1 (ref) 1 (ref) 76 1 (ref) 1 (ref)
Quintile 2 122.3–200.2 342 0.97 (0.84–1.13) 1.07 (0.92–1.25) 306 0.97 (0.83–1.13) 1.07 (0.91–1.25) 97 0.96 (0.73–1.27) 1.07 (0.80–1.42) 83 1.13 (0.83–1.55) 1.29 (0.94–1.77)
Quintile 3 200.3–311.1 267 0.74 (0.63–0.88) 0.86 (0.72–1.01) 238 0.74 (0.62–0.89) 0.86 (0.72–1.03) 70 0.71 (0.52–0.97) 0.83 (0.60–1.14) 77 1.02 (0.73–1.41) 1.23 (0.88–1.72)
Quintile 4 311.2–555.9 297 0.75 (0.63–0.89) 0.90 (0.77–1.07) 264 0.76 (0.63–0.90) 0.91 (0.76–1.09) 76 0.75 (0.54–1.03) 0.90 (0.65–1.26) 82 0.95 (0.67–1.33) 1.22 (0.86–1.73)
Quintile 5 >555.9 324 0.75 (0.62–0.90) 0.91 (0.75–1.10) 299 0.75 (0.62–0.90) 0.91 (0.75–1.12) 83 0.71 (0.50–1.00) 0.89 (0.62–1.27) 95 1.00 (0.70–1.44) 1.33 (0.92–1.94)
P-trend     0.002 0.25   <0.004 0.30   0.05 0.45   0.76 0.32
Continuous (log2)     0.91 (0.87–0.95) 0.97 (0.92–1.02)   0.91 (0.87–0.95) 0.97 (0.92–1.02)   0.90 (0.83–0.98) 0.97 (0.88–1.06)   0.98 (0.90–1.08) 1.07 (0.97–1.18)
Flavan-3-ol monomers
Quintile 1 <19.3 295 1 (ref) 1 (ref) 263 1 (ref) 1 (ref) 72 1 (ref) 1 (ref) 64 1 (ref) 1 (ref)
Quintile 2 19.3–33.8 318 0.84 (0.71–0.99) 0.91 (0.77–1.07) 284 0.83 (0.70–0.98) 0.91 (0.76–1.08) 90 0.94 (0.69–1.29) 1.04 (0.76–1.43) 75 0.92 (0.66–1.29) 1.04 (0.74–1.46)
Quintile 3 33.9–79.7 369 0.82 (0.70–0.96) 0.89 (0.76–1.06) 336 0.84 (0.71–1.00) 0.92 (0.77–1.10) 107 1.00 (0.73–1.37) 1.11 (0.81–1.54) 110 1.13 (0.82–1.56) 1.32 (0.95–1.84)
Quintile 4 79.8–376.0 263 0.72 (0.60–0.86) 0.83 (0.69–1.01) 234 0.71 (0.59–0.86) 0.83 (0.68–1.01) 71 0.79 (0.55–1.14) 0.95 (0.65–1.37) 76 0.99 (0.69–1.42) 1.24 (0.85–1.80)
Quintile 5 >376.0 330 0.74 (0.60–0.90) 0.90 (0.73–1.11) 308 0.74 (0.60–0.91) 0.90 (0.72–1.12) 90 0.80 (0.54–1.17) 1.02 (0.68–1.51) 88 0.93 (0.62–1.42) 1.23 (0.80–1.88)
P-trend     0.05 0.71   0.05 0.68   0.21 0.81   0.61 0.66
Continuous (log2)     0.95 (0.92–0.98) 0.98 (0.95–1.01)   0.94 (0.91–0.98) 0.98 (0.95–1.01)   0.95 (0.89–1.01) 0.99 (0.93–1.05)   0.99 (0.93–1.06) 1.04 (0.97–1.11)
Proanthocyanidins
Quintile 1 <82.8 370 1 (ref) 1 (ref) 341 1 (ref) 1 (ref) 114 1 (ref) 1 (ref) 78 1 (ref) 1 (ref)
Quintile 2 82.8–125.9 306 0.83 (0.71–0.97) 0.93 (0.79–1.08) 281 0.84 (0.72–0.99) 0.94 (0.80–1.11) 83 0.77 (0.58–1.03) 0.87 (0.65–1.16) 95 1.49 (1.1–2.02) 1.49 (1.10–2.02)
Quintile 3 126.0–171.9 303 0.84 (0.72–0.99) 0.97 (0.83–1.14) 277 0.86 (0.73–1.02) 1.00 (0.84–1.18) 99 0.96 (0.73–1.27) 1.12 (0.85–1.50) 75 1.32 (0.94–1.84) 1.32 (0.94–1.84)
Quintile 4 172.0–239.4 273 0.76 (0.65–0.90) 0.91 (0.76–1.08) 241 0.77 (0.64–0.91) 0.91 (0.76–1.09) 62 0.64 (0.46–0.88) 0.76 (0.54–1.07) 68 1.24 (0.87–1.77) 1.24 (0.87–1.77)
Quintile 5 >239.4 323 0.73 (0.62–0.87) 0.87 (0.73–1.05) 285 0.75 (0.63–0.90) 0.90 (0.74–1.09) 72 0.70 (0.50–0.98) 0.84 (0.59–1.20) 97 1.38 (0.96–1.99) 1.38 (0.96–1.99)
P-trend     <0.001 0.17   0.003 0.28   0.029 0.29   0.59 0.33
Continuous (log2)     0.91 (0.86–0.96) 0.97 (0.92–1.03)   0.91 (0.86–0.96) 0.97 (0.92–1.03)   0.90 (80.82–0.99) 0.97 (0.87–1.07)   1.01 (0.91–1.12) 1.12 (1.00–1.25)
Theaflavins
Quintile 1 0 685 1 (ref) 1 (ref) 615 1 (ref) 1 (ref) 176 1 (ref) 1 (ref) 179 1 (ref) 1 (ref)
Quintile 2 0.1–0.6 225 0.82 (0.68–0.98) 0.86 (0.72–1.03) 203 0.86 (0.71–1.04) 0.91 (0.75–1.10) 67 0.92 (0.65–1.29) 0.97 (0.69–1.37) 53 0.96 (0.66–1.40) 1.01 (0.69–1.48)
Quintile 3 0.7–5.2 221 0.84 (0.70–1.00) 0.93 (0.78–1.11) 191 0.83 (0.69–1.01) 0.93 (0.77–1.13) 64 0.94 (0.67–1.31) 1.06 (0.75–1.49) 58 1.04 (0.73–1.49) 1.18 (0.82–1.69)
Quintile 4 5.3–14.7 217 0.75 (0.61–0.91) 0.88 (0.72–1.07) 203 0.77 (0.62–0.95) 0.91 (0.73–1.12) 57 0.79 (0.54–116) 0.94 (0.64–1.39) 67 1.06 (0.72–1.57) 1.28 (087–1.90)
Quintile 5 >14.7 227 0.72 (0.59–0.88) 0.86 (0.70–1.06) 213 0.74 (0.60–0.92) 0.89 (0.72–1.10) 66 0.77 (0.53–1.11) 0.94 (0.65–1.37) 56 0.80 (0.53–1.20) 0.97 (0.64–1.46)
P-trend     0.07 0.79   0.10 0.87   0.35 0.95   0.63 0.71
Continuous (log2)     0.98 (0.97–0.99) 0.99 (0.98–1.01)   0.98 (0.97–1.00) 0.99 (0.98–1.01)   0.99 (0.97–1.01) 1.00 (0.98–1.02)   1.00 (0.97–1.02) 1.01 (0.99–1.04)
Anthocyanidins
Quintile 1 <11.4 389 1 (ref) 1 (ref) 364 1 (ref) 1 (ref) 120 1 (ref) 1 (ref) 98 1 (ref) 1 (ref)
Quintile 2 11.4–18.6 365 1.04 (0.90–1.20) 1.15 (0.99–1.33) 333 1.03 (0.89–1.20) 1.14 (0.98–1.33) 105 1.05 (0.81–1.37) 1.17 (0.90–1.54) 90 1.09 (0.82–1.45) 1.24 (0.92–1.66)
Quintile 3 18.7–27.1 297 0.92 (0.78–1.07) 1.03 (0.88–1.21) 270 0.92 (0.78–1.08) 1.03 (0.88–1.22) 67 0.75 (0.56–1.02) 0.86 (0.63–1.17) 85 1.14 (0.84–1.53) 1.33 (0.98–1.80)
Quintile 4 27.2–41.6 289 0.99 (0.84–1.16) 1.12 (0.95–1.33) 246 0.94 (0.80–1.12) 1.08 (0.90–1.28) 76 1.03 (0.76–1.39) 1.17 (0.85–1.60) 66 1.00 (0.72–1.39) 1.21 (0.86–1.69)
Quintile 5 >41.6 235 0.94 (0.78–1.12) 1.05 (0.87–1.27) 212 0.97 (0.80–1.17) 1.09 (0.90–1.33) 62 1.06 (0.75–1.50) 1.20 (0.84–1.72) 74 1.21 (0.86–1.69) 1.46 (1.03–2.09)
P-trend     0.40 0.81   0.56 0.62   0.78 0.37   0.40 0.07
Continuous (log2)     0.97 (0.92–1.01) 1.02 (0.97–1.07)   0.97 (0.93–1.02) 1.02 (0.97–1.07)   0.96 (0.88–1.05) 1.01 (0.93–1.11)   1.05 (0.96–1.15) 1.13 (1.03–1.24)
Flavonols
Quintile 1 <12.9 353 1 (ref) 1 (ref) 319 1 (ref) 1 (ref) 101 1 (ref) 1 (ref) 77 1 (ref) 1 (ref)
Quintile 2 12.9–18.4 343 0.87 (0.74–1.01) 0.91 (0.78–1.06) 308 0.88 (0.75–1.03) 0.92 (0.79–1.09) 108 0.98 (0.74–1.30) 1.04 (0.78–1.37) 77 0.92 (0.67–1.28) 1.02 (0.74–1.41)
Quintile 3 18.5–25.9 300 0.75 (0.64–0.89) 0.81 (0.68–0.95) 268 0.78 (0.65–0.92) 0.84 (0.70–1.00) 71 0.65 (0.47–0.89) 0.69 (0.50–0.96) 91 1.08 (0.78–1.48) 1.25 (0.90–1.73)
Quintile 4 26.0–38.5 302 0.77 (0.65–0.91) 0.84 (0.70–1.00) 276 0.81 (0.67–0.96) 0.88 (0.73–1.07) 82 0.78 (0.55–1.06) 0.83 (0.59–1.16) 96 1.12 (0.80–1.57) 1.35 (0.95–1.91)
Quintile 5 >38.5 277 0.67 (0.56–0.81) 0.75 (0.61–0.91) 254 0.68 (0.56–0.84) 0.76 (0.62–0.94) 68 0.58 (0.41–0.84) 0.64 (0.44–0.95) 72 0.79 (0.54–1.16) 0.99 (0.66–1.48)
P-trend     <0.001 0.009   <0.001 0.022   0.003 0.020   0.26 0.88
Continuous (log2)     0.88 (0.82–0.94) 0.92 (0.86–0.99)   0.89 (0.82–0.95) 0.93 (0.86–1.00)   0.86 (0.75–0.97) 0.90 (0.79–1.03)   0.95 (0.83–1.08) 1.04 (0.90–1.19)
Flavanones
Quintile 1 <5.7 362 1 (ref) 1 (ref) 340 1 (ref) 1 (ref) 100 1 (ref) 1 (ref) 95 1 (ref) 1 (ref)
Quintile 2 5.7–11.9 316 1.03 (0.88–1.20) 1.11 (0.95–1.29) 281 0.99 (0.84–1.16) 1.07 (0.91–1.26) 84 0.96 (0.72–1.29) 1.06 (0.79–1.42) 78 1.05 (0.77–1.42) 1.15 (0.85–1.57)
Quintile 3 12.0–20.0 277 0.91 (0.78–1.07) 1.01 (0.86–1.18) 251 0.92 (0.77–1.08) 1.01 (0.85–1.19) 81 0.99 (0.74–1.34) 1.11 (0.82–1.50) 73 1.02 (0.74–1.39) 1.15 (0.84–1.58)
Quintile 4 20.1–33.0 322 1.02 (0.87–1.19) 1.14 (0.97–1.34) 292 1.03 (0.87–1.21) 1.15 (0.98–1.36) 87 1.06 (0.79–1.43) 1.21 (0.90–1.64) 92 1.16 (0.86–1.57) 1.34 (0.99–1.82)
Quintile 5 >33.0 298 0.91 (0.76–1.07) 1.04 (0.87–1.24) 261 0.89 (0.75–1.07) 1.03 (0.85–1.23) 78 0.98 (0.71–1.36) 1.14 (0.82–1.59) 75 0.89 (0.63–1.25) 1.08 (0.76–1.52)
P-trend     0.26 0.75   0.32 0.70   0.91 0.36   0.56 0.65
Continuous (log2)     0.99 (0.96–1.02) 1.02 (0.99–1.05)   0.99 (0.96–1.02) 1.02 (0.99–1.06)   1.01 (0.95–1.07) 1.05 (0.98–1.11)   1.00 (0.95–1.06) 1.04 (0.98–1.11)
Flavones
Quintile 1 <1.1 388 1 (ref) 1 (ref) 355 1 (ref) 1 (ref) 115 1 (ref) 1 (ref) 99 1 (ref) 1 (ref)
Quintile 2 1.1–1.9 300 0.73 (0.62–0.85) 0.81 (0.69–0.95) 279 0.77 (0.65–0.91) 0.86 (0.73–1.02) 88 0.76 (0.57–1.02) 0.87 (0.65–1.16) 78 0.82 (0.59–1.12) 0.93 (0.67–1.28)
Quintile 3 2.0–3.0 310 0.76 (0.64–0.89) 0.87 (0.73–1.02) 285 0.80 (0.67–0.95) 0.92 (0.77–1.09) 84 0.76 (0.56–1.04) 0.89 (0.65–1.21) 86 0.92 (0.66–1.27) 1.08 (0.78–1.50)
Quintile 4 3.1–5.0 250 0.70 (0.59–0.83) 0.81 (0.68–0.97) 227 0.74 (0.62–0.89) 0.87 (0.77–1.04) 64 0.69 (0.50–0.96) 0.82 (0.58–1.15) 65 0.79 (0.56–1.12) 0.96 (0.68–1.36)
Quintile 5 >5.0 327 0.78 (0.66–0.93) 0.90 (0.76–1.08) 279 0.81 (0.67–0.97) 0.94 (0.78–1.13) 79 0.88 (0.64–1.23) 1.04 (0.74–1.45) 85 0.87 (0.62–1.22) 1.05 (0.74–1.50)
P-trend     0.10 0.73   0.14 0.85   0.73 0.63   0.63 0.68
Continuous (log2)     0.95 (0.91–0.99) 0.99 (0.95––1.03)   0.95 (0.91–0.99) 0.99 (0.95–1.04)   0.96 (0.89–1.03) 1.01 (0.93–1.08)   0.99 (0.91–1.07) 1.04 (0.96–1.13)
Isoflavones
Quintile 1 <0.2 203 1 (ref) 1 (ref) 174 1 (ref) 1 (ref) 58 1 (ref) 1 (ref) 47 1 (ref) 1 (ref)
Quintile 2 0.2–0.4 362 1.06 (0.88–1.28) 1.01 (0.83–1.22) 327 1.04 (0.85–1.27) 0.99 (0.81–1.21) 99 0.92 (0.65–1.30) 0.85 (0.60–1.21) 104 1.08 (0.75–1.55) 1.06 (0.74–1.53)
Quintile 3 0.5–0.6 388 1.09 (0.90–1.32) 1.01 (0.83–1.23) 345 1.03 (0.84–1.27) 0.96 (0.77–1.18) 107 0.97 (0.68–1.38) 0.85 (0.59–1.23) 109 1.03 (0.71–1.49) 1.01 (0.69–1.49)
Quintile 4 0.7–1.4 358 1.06 (0.86–1.31) 1.01 (0.81–1.26) 332 1.04 (0.83–1.29) 0.98 (0.78–1.24) 93 0.92 (0.62––1.36) 0.83 (0.55–1.26) 90 0.93 (0.62–1.40) 0.96 (0.62–1.47)
Quintile 5 >1.4 264 0.98 (0.77–1.25) 0.93 (0.72–1.21) 247 0.98 (0.76–1.26) 0.93 (0.71–1.22) 73 1.02 (0.65–1.59) 0.91 (0.56–1.48) 63 0.88 (0.55–1.41) 0.93 (0.56–1.55)
P-trend     0.42 0.41   0.57 0.57   0.67 0.76   0.39 0.64
Continuous (log2)     0.98 (0.93–1.04) 0.97 (0.92–1.03)   0.98 (0.92–1.04) 0.97 (0.91–1.03)   1.02 (0.92–1.13) 1.00 (0.89–1.12)   0.90 (0.80–1.00) 0.90 (0.79–1.02)
Lignans
Quintile 1 <0.9 323 1 (ref) 1 (ref) 296 1 (ref) 1 (ref) 96 1 (ref) 1 (ref) 81 1 (ref) 1 (ref)
Quintile 2 0.9–1.1 295 0.89 (0.75–1.04) 0.91 (0.77–1.07) 263 0.88 (0.74–1.05) 0.90 (0.76–1.07) 81 0.81 (0.59–1.09) 0.81 (0.60–1.10) 82 1.08 (0.78–1.47) 1.15 (0.83–1.58)
Quintile 3 1.2–1.4 283 0.81 (0.68–0.96) 0.83 (0.70–0.99) 250 0.81 (0.67–0.97) 0.83 (0.69–1.00) 68 0.63 (0.45–0.88) 0.63 (0.44–0.89) 70 0.91 (0.65–1.28) 1.00 (0.71–1.43)
Quintile 4 1.5–2.0 327 0.83 (0.69–1.00) 0.86 (0.71–1.04) 294 0.83 (0.68–1.01) 0.86 (0.70–1.05) 86 0.66 (0.46–0.93) 0.65 (0.45–0.94) 93 1.09 (0.76–1.55) 1.23 (0.85–1.79)
Quintile 5 >2.0 347 0.76 (0.62–0.92) 0.78 (0.62–0.96) 322 0.77 (0.63–0.95) 0.79 (0.63–1.00) 99 0.61 (0.42–0.89) 0.59 (0.39–0.89) 87 0.87 (0.59–1.29) 1.02 (0.67–1.57)
P-trend     0.015 0.042   0.037 0.09   0.032 0.035   0.40 0.93
Continuous (log2)     0.89 (0.82–0.98) 0.91 (0.82–1.00)   0.90 (0.82–0.99) 0.92 (0.83–1.02)   0.87 (0.73–1.04) 0.87 (0.72–1.06)   0.90 (0.75–1.07) 0.97 (0.80–1.18)

Abbreviations: BMI=body mass index; CI=confidence interval; EPIC=European Prospective Investigation into Cancer and Nutrition study; HR=hazard ratio; UCC=urothelial cell carcinoma.

Crude: stratified by sex, age (1 year) and centre.

Multivariable: stratified by sex, age (1 year) and centre and adjusted for energy, smoking intensity, BMI, physical activity, alcohol intake and highest educational level.