TABLE 4.
Hazard ratios (95% confidence intervals) of colorectal cancer according to anatomic subsites associated with circulating levels of liver function markers a
| Biomarker | Proximal colon cancer (n = 907) | Distal colon cancer (n = 791) | Rectal cancer (n = 912) | P for heterogeneity b |
|---|---|---|---|---|
| Alanine transaminase (ALT) | ||||
| HR (95% CI), decile 10 vs 1 | 0.55 (0.39-0.76) | 0.64 (0.46-0.90) | 0.65 (0.47-0.91) | .73 |
| HR (95% CI), per 1-SD increment | 0.84 (0.77-0.91) | 0.91 (0.84-0.99) | 0.87 (0.81-0.95) | .37 |
| Aspartate transaminase (AST) | ||||
| HR (95% CI), decile 10 vs 1 | 0.58 (0.42-0.80) | 0.65 (0.47-0.89) | 0.65 (0.48-0.87) | .86 |
| HR (95% CI), per 1-SD increment | 0.90 (0.83-0.96) | 0.93 (0.86-1.00) | 0.91 (0.85-0.98) | 0.84 |
| Total bilirubin (TBIL) | ||||
| HR (95% CI), decile 10 vs 1 | 0.76 (0.56-1.02) | 1.00 (0.72-1.39) | 0.89 (0.66-1.21) | .46 |
| HR (95% CI), per 1-SD increment | 0.97 (0.90-1.05) | 1.00 (0.93-1.08) | 0.98 (0.91-1.05) | .85 |
| Gamma glutamyltransferase (GGT) | ||||
| HR (95% CI), decile 10 vs 1 | 0.62 (0.45-0.87) | 0.61 (0.43-0.86) | 0.88 (0.64-1.21) | .21 |
| HR (95% CI), per 1-SD increment | 0.88 (0.81-0.94) | 0.99 (0.92-1.07) | 1.04 (0.98-1.11) | .004 |
| Alkaline phosphatase (ALP) | ||||
| HR (95% CI), decile 10 vs 1 | 1.19 (0.87-1.63) | 0.90 (0.66-1.23) | 1.05 (0.78-1.41) | .46 |
| HR (95% CI), per 1-SD increment | 1.05 (0.99-1.13) | 0.96 (0.89-1.04) | 1.02 (0.95-1.09) | .21 |
| Total protein (TP) | ||||
| HR (95% CI), decile 10 vs 1 | 0.68 (0.51-0.91) | 0.63 (0.46-0.88) | 0.82 (0.60-1.11) | .51 |
| HR (95% CI), per 1-SD increment | 0.89 (0.84-0.96) | 0.90 (0.84-0.97) | 0.93 (0.87-1.00) | .68 |
| Albumin (ALB) | ||||
| HR (95% CI), decile 10 vs 1 | 0.56 (0.40-0.78) | 0.68 (0.49-0.95) | 0.76 (0.56-1.02) | .41 |
| HR (95% CI), per 1-SD increment | 0.88 (0.82-0.94) | 0.92 (0.85-0.99) | 0.93 (0.87-0.99) | .54 |
Abbreviations: CI, confidence interval; HR, hazard ratio.
Cases with cancers in more than one site were counted multiple times. Multivariable Cox regression model with age as the underlying timescale was used and adjusted for sex, race (white, non-white, unknown), fasting status, age at recruitment, Townsend deprivation index (continuous), waist circumference/hip circumference (continuous), height (continuous), BMI (continuous), C-reactive protein (continuous), total physical activity (quintile), alcohol status and consumption frequency (never, former, current—special occasions only, current—1-3 times per month, current—1-2 times per week, current—3-4 times per week, current—daily/almost daily, unknown), smoking status and intensity (never, former, current—<15 per day, current—≥15 per day, current—intensity unknown, unknown), frequency of red and processed meat consumption (never, <1, =1, 2-4, 5-6, ≥7 occasions per week, unknown), frequency of oily fish consumption (never, <1, =1, 2-4, 5-6, ≥7 occasions per week, unknown), family history of cancer (no, yes, unknown), educational level (college/university degree, non-college/university degree, unknown), regular aspirin use (no, yes, unknown), bowel cancer screening (no, yes, unknown) and overall health ranking (excellent, good, fair, poor, unknown).
P heterogeneity for proximal colon vs distal colon vs rectal cancer was calculated using the contrast method based on a fully unconstrained approach.