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. Author manuscript; available in PMC: 2019 Sep 25.
Published in final edited form as: Eur J Epidemiol. 2018 May 14;33(11):1063–1075. doi: 10.1007/s10654-018-0408-6

Table 3. Hazard ratios (95% CIs) for colorectal cancer and subsites, according to double the intake of polyphenol classes and subclasses by sex in the EPIC study.

Women Men
Intake (mg/d) median (P 5%-P 95%) Colorectal HR (95% CI) Colon HR (95% CI) Rectum HR (95% CI) P-value1 Intake (mg/d) median (P 5%-P 95%) Colorectal HR (95% CI) Colon HR (95% CI) Rectum HR (95% CI) P-value1 P-value2
Flavonoid subclasses 419.7 (116.3-1238.9) 1.03 (0.98-1.08) 1.00 (0.95-1.06) 1.09 (1.00-1.18)* 0.10 418.8 (117.4-1245.8) 1.00 (0.96-1.05) 1.00 (0.94-1.06) 1.01 (0.94-1.09) 0.87 0.030
      Anthocyanins 25.5 (3.7-116.1) 1.01 (0.99-1.04) 1.00 (0.97-1.03) 1.02 (0.97-1.06) 0.46 22.9 (2.8-120.5) 0.99 (0.97-1.01) 1.00 (0.97-1.02) 0.98 (0.95-1.01) 0.49 0.09
      Dihydrochalcones 1.8 (0.1-6.3) 1.00 (0.99-1.02) 1.00 (0.99-1.02) 1.01 (0.98-1.03) 0.76 1.5 (0.1-6.9) 1.00 (0.99-1.01) 0.99 (0.98-1.01) 1.00 (0.98-1.01) 0.61 0.038
      Dihydroflavonols 0.4 (0.0-9.6) 1.00 (1.00-1.01) 1.00 (0.99-1.00) 1.00 (0.99-1.01) 0.20 1.0 (0.0-18.4) 0.99 (0.99-1.00) 0.99 (0.99-1.00) 0.99 (0.98-1.00) 0.64 0.027
      Flavanols 285.6 (62.4-1015.5) 1.02 (0.98-1.06) 1.00 (0.95-1.04) 1.05 (0.98-1.13) 0.19 283.5 (65.1-1028.8) 1.01 (0.97-1.05) 0.99 (0.94-1.04) 1.01 (0.95-1.08) 0.51 0.043
            Flavan-3-ol monomers 39.8 (6.4-460.4) 1.01 (0.99-1.03) 0.99 (0.97-1.02) 1.04 (1.00-1.09) 0.08 42.8 (7.4-466.1) 1.00 (0.97-1.02) 0.99 (0.96-1.02) 1.00 (0.96-1.04) 0.63 0.08
            Proanthocyanidins 202.9 (52.4-532.0) 1.04 (0.99-1.08) 1.01 (0.96-1.07) 1.06 (0.98-1.15) 0.29 203.7 (51.5-552.1) 1.00 (0.96-1.05) 0.99 (0.93-1.04) 1.00 (0.93-1.07) 0.56 0.020
            Theaflavins 1.6 (0.0-106.4) 1.00 (1.00-1.01) 1.00 (1.00-1.00) 1.01 (1.00-1.01) 0.26 1.5 (0.0-112.0) 1.00 (1.00-1.01) 1.00 (1.00-1.01) 1.00 (1.00-1.01) 0.74 0.06
      Flavanones 25.6 (1.8-118.3) 1.00 (0.99-1.02) 0.99 (0.97-1.02) 1.03 (1.00-1.07)* 0.05 24.2 (2.2-120.0) 0.99 (0.97-1.01) 0.99 (0.96-1.01) 1.00 (0.96-1.03) 0.69 0.10
      Flavones 9.3 (2.7-26.6) 1.02 (0.98-1.06) 1.02 (0.97-1.07) 1.02 (0.95-1.10) 0.09 9.4 (2.3-30.4) 0.98 (0.94-1.03) 0.96 (0.91-1.02) 0.97 (0.90-1.04) 0.42 0.027
      Flavonols 27.9 (6.9-112.0) 1.01 (0.97-1.05) 0.99 (0.94-1.04) 1.07 (0.99-1.15) 0.08 29.5 (7.9-113.3) 1.01 (0.96-1.05) 0.99 (0.94-1.05) 1.00 (0.93-1.07) 0.57 0.23
      Isoflavonoids 0.0 (0.0-7.3) 1.01 (1.00-1.02) 1.01 (1.00-1.02) 1.00 (0.99-1.02) 0.48 0.0 (0.0-5.0) 0.99 (0.98-1.01) 0.99 (0.98-1.00) 1.00 (0.98-1.02) 0.28 0.001
Phenolic acid subclasses 508.2 (122.8-1317.8) 1.03 (0.99-1.08) 1.00 (0.95-1.05) 1.10 (1.02-1.19)* 0.038 561.9 (162.1-1395.7) 0.96 (0.91-1.01) 0.91 (0.85-0.97)** 1.04 (0.95-1.14) 0.015 0.001
    Hydroxybenzoics 19.5 (1.3-155.0) 1.00 (0.98-1.03) 0.99 (0.96-1.02) 1.05 (1.00-1.10)* 0.03 23.0 (3.1-159.5) 1.00 (0.97-1.04) 1.00 (0.96-1.04) 1.01 (0.96-1.06) 0.93 0.10
    Hydroxycinnamic 474.6 (95.5-1279.3) 1.02 (0.98-1.06) 1.01 (0.96-1.05) 1.07 (1.00-1.15)* 0.10 513.6 (118.2-1356.5) 0.96 (0.92-1.01) 0.92 (0.87-0.97)** 1.03 (0.96-1.11) 0.017 0.002
    Hydroxyphenylacetic 0.1 (0.0-0.6) 0.99 (0.98-1.01) 0.99 (0.98-1.01) 1.00 (0.98-1.03) 0.54 0.2 (0.0-1.3) 1.00 (0.98-1.01) 0.99 (0.97-1.01) 0.98 (0.96-1.01) 0.12 0.40
Stilbenes 0.4 (0.0-6.6) 1.00 (0.98-1.01) 1.00 (0.98-1.02) 1.00 (0.97-1.03) 0.74 0.8 (0.0-11.8) 0.98 (0.96-0.99) 0.98 (0.96-1.00) 0.97 (0.95-1.00) 0.70 0.042
Lignans 1.4 (0.7-4.9) 1.01 (0.94-1.08) 0.98 (0.90-1.06) 1.08 (0.95-1.21) 0.20 1.6 (0.8-5.3) 1.06 (0.98-1.15) 1.11 (1.01-1.22) 0.99 (0.86-1.13) 0.17 0.83
Other polyphenol classes
     Alkylphenols 24.4 (2.0-80.1) 1.00 (0.97-1.03) 1.00 (0.97-1.04) 1.00 (0.95-1.06) 0.95 39.7 (2.3-113.5) 0.99 (0.96-1.02) 0.99 (0.95-1.02) 1.01 (0.95-1.06) 0.57 < 0.001
     Tyrosol 3.5 (0.3-30.2) 0.99 (0.97-1.00) 0.99 (0.97-1.01) 0.97 (0.94-1.00) 0.26 4.5 (0.4-49.8) 0.99 (0.97-1.01) 1.00 (0.97-1.02) 0.97 (0.94-1.00) 0.22 0.20
     Alkymethoxyphenols 2.2 (0.1-6.2) 1.01 (0.99-1.02) 1.00 (0.98-1.02) 1.04 (1.00-1.08)* 0.036 2.7 (0.3-7.3) 0.99 (0.98-1.01) 0.99 (0.97-1.01) 1.00 (0.97-1.03) 0.49 0.005
     Furanocoumarins 0.0 (0.0-0.4) 1.00 (0.99-1.00) 1.00 (0.99-1.01) 0.99 (0.98-1.00) 0.39 0.0 (0.0-0.3) 1.00 (0.99-1.01) 1.00 (0.99-1.01) 1.01 (0.99-1.02) 0.31 0.87
     Hydroxybenzaldehydes 0.1 (0.0-1.5) 0.99 (0.98-1.01) 0.99 (0.98-1.01) 1.01 (0.98-1.03) 0.39 0.3 (0.0-2.5) 0.99 (0.98-1.01) 0.98 (0.96-1.00) 0.97 (0.95-1.00)* 0.10 0.008
     Hydroxycoumarins 0.0 (0.0-0.4) 0.99 (0.99-1.00) 1.00 (0.99-1.01) 0.99 (0.98-1.01) 0.42 0.2 (0.0-1.3) 1.00 (0.99-1.01) 0.99 (0.98-1.01) 0.99 (0.98-1.00) 0.13 0.003
     Hydroxyphenylpropenes 0.0 (0.0-4.0) 1.00 (1.00-1.01) 1.00 (1.00-1.01) 1.00 (0.99-1.01) 0.59 0.2 (0.0-5.8) 1.00 (1.00-1.01) 1.01 (1.00-1.01) 1.00 (0.99-1.01) 0.22 0.18
     Methoxyphenols 0.3 (0.0-0.8) 1.01 (1.00-1.02) 1.00 (0.99-1.01) 1.02 (1.00-1.03)* 0.17 0.3 (0.0-0.8) 0.99 (0.98-1.00) 0.99 (0.98-1.00)** 0.99 (0.98-1.00) 0.73 < 0.001
*

P-value<0.05

**

P-value<0.01; any association exceeds the Bonferroni threshold (P<0.05/26) < 0.002

1

P-value for heterogeneity for colon vs rectum cancer

2

P-value for interaction by sex in colorectal cancer

Cox model was stratified by age and centre, and additionally adjusted for smoking status and intensity, physical activity, education level, body mass index, total energy intake, alcohol, red and processed meat, fibre (g/d) and calcium (mg/d) intakes and in women also for menopausal status, hormone replacement therapy use, and oral contraceptive use