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Table 3 The association between unconjugated bilirubin (UCB) levels and colorectal cancer risk across strata of potential effect modifiers in the EPIC study

From: Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses

Colorectal cancer
Variables Men Women
n cases/controls Odds ratio (95% CI) P Pheterogeneity n cases/controls Odds ratio (95% CI) P Pheterogeneity
Adjusted model 658/658 1.19 (1.04–1.36) 0.01   728/728 0.86 (0.76–0.97) 0.02  
Age at blood collection (year, median) 658/658    0.30 728/728    0.008
< 59.2/< 58.5 329/329 1.28 (1.06–1.54)    364/364 1.01 (0.85–1.19) > 0.90  
≥ 59.2/≥ 58.5 329/329 1.10 (0.92–1.32)    364/364 0.73 (0.61–0.87) 0.001  
rs6431625 (increasing levels C allele) 333/333    0.02 428/428    0.14
TT genotype (wild-type) 117/139 1.1 (0.73–1.65) 0.60   168/151 0.69 (0.49–0.99) 0.04  
TC genotype 160/146 0.92 (0.64–1.32) 0.60   194/206 0.71 (0.53–0.95) 0.02  
CC genotype 56/48 2.01 (1.26–3.20) 0.003   66/71 1.06 (0.74–1.53) 0.7  
Smoking status 658/658    0.40 728/728    0.20
 Never 170/170 1.26 (1.00–1.59) 0.05   427/427 0.83 (0.71–0.98) 0.03  
 Former 294/294 1.06 (0.86–1.30) 0.60   160/160 0.84 (0.66–1.07) 0.20  
 Current 182/182 1.33 (1.08–1.64) 0.01   137/137 0.99 (0.78–1.25) 0.90  
 Unknown 12/12 0.93 (0.35–2.49) 0.90   4/4 0.05 (0.00–0.1) 0.20  
Follow-up time (years) 658/658    0.20 728/728    0.60
 1 (< 2) 141/141 0.96 (0.74–1.25) 0.80   158/158 0.82 (0.65–1.05) 0.10  
 2 (2–4) 173/173 1.34 (1.04–1.72) 0.02   160/160 0.96 (0.76–1.23) 0.80  
 3 (> 4) 244/244 1.23 (1.03–1.50) 0.02   280/380 0.84 (0.71–0.99) 0.04  
  1. No effect modifications by BMI (median), alcohol consumption (median), menopausal status, and use of HT were observed (all P ≥ 0.7)
  2. Abbreviations: n number, P P value, CI confidence interval
  3. Cases matched 1:1 to control subjects. EPIC (European Prospective Investigation into Cancer and Nutrition): Conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between log-transformed UCB levels (log-UCB), standardized per one standard deviation (1-SD) increments, and CRC risk. The crude model was conditioned on the matching factors including study center, age at blood collection (1 year), fasting status and time (3 h intervals) at blood collection, among women, additionally by menopausal status (pre-, peri-, and post-menopausal or surgically menopausal), and hormone therapy (HT) (yes, no). The multivariable model was adjusted for level of education (none/primary school, technical/professional, secondary school, university degree), BMI, height, smoking status (never, former, current smoker), physical activity (inactive, moderately inactive, moderately active, active), alcohol consumption (g/day), dietary intakes of fiber (g/day), red meat (g/day), processed meats (g/day), dairy products (g/day), and total energy intake (kcal/day)