TABLE 3.
Hazard ratios (95% confidence intervals) of colorectal cancer associated with circulating levels of liver function markers in the UK Biobank
| Decile 1 | Decile 2 | Decile 3 | Decile 4 | Decile 5 | Decile 6 | Decile 7 | Decile 8 | Decile 9 | Decile 10 | P for overall significance | P for nonlinear relation | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alanine transaminase (ALT) | ||||||||||||
| Median, range | 11 (3-12) | 13 (12-14) | 15 (14-16) | 17 (16-18) | 19 (18-20) | 21 (20-22) | 24 (22-25) | 27 (25-29) | 32 (29-36) | 44 (36-82) | ||
| CRC cases | 238 | 280 | 265 | 285 | 262 | 237 | 310 | 301 | 257 | 227 | ||
| Person-years | 369 535 | 369 684 | 372 999 | 369 511 | 371 519 | 371 265 | 371 230 | 370 421 | 372 275 | 372 948 | ||
| HR (95% CI)a | 1 (referent) | 1.04 (0.87-1.23) | 0.88 (0.74-1.05) | 0.90 (0.76-1.07) | 0.79 (0.66-0.94) | 0.70 (0.58-0.83) | 0.89 (0.75-1.06) | 0.86 (0.72-1.02) | 0.76 (0.64-0.91) | 0.73 (0.60-0.88) | <.001 | .01 |
| HR (95% CI)b | 1 (referent) | 1.03 (0.87-1.23) | 0.87 (0.73-1.03) | 0.87 (0.73-1.04) | 0.75 (0.63-0.90) | 0.65 (0.54-0.78) | 0.82 (0.69-0.98) | 0.77 (0.65-0.92) | 0.67 (0.56-0.81) | 0.62 (0.51-0.75) | <.001 | .005 |
| HR (95% CI)c | 1 (referent) | 1.06 (0.76-1.49) | 0.75 (0.53-1.06) | 0.76 (0.54-1.07) | 0.57 (0.40-0.81) | 0.43 (0.30-0.62) | 0.68 (0.48-0.95) | 0.60 (0.43-0.85) | 0.46 (0.32-0.65) | 0.39 (0.27-0.57) | ||
| Aspartate transaminase (AST) | ||||||||||||
| Median, range | 17 (3-18) | 19 (18-20) | 21 (20-22) | 22 (22-23) | 24 (23-24) | 25 (24-26) | 27 (26-27) | 29 (28-30) | 31 (30-34) | 38 (34-62) | ||
| CRC cases | 252 | 262 | 243 | 292 | 282 | 222 | 317 | 293 | 251 | 248 | ||
| Person-years | 375 686 | 372 399 | 362 181 | 389 996 | 370 511 | 352 723 | 384 094 | 367 621 | 364 257 | 371 919 | ||
| HR (95% CI)a | 1 (referent) | 0.87 (0.74-1.04) | 0.77 (0.65-0.92) | 0.81 (0.69-0.96) | 0.79 (0.66-0.93) | 0.62 (0.52-0.75) | 0.81 (0.68-0.95) | 0.77 (0.65-0.91) | 0.66 (0.55-0.79) | 0.64 (0.54-0.77) | <.001 | .001 |
| HR (95% CI)b | 1 (referent) | 0.88 (0.74-1.05) | 0.78 (0.65-0.93) | 0.82 (0.69-0.98) | 0.80 (0.67-0.95) | 0.63 (0.53-0.76) | 0.82 (0.69-0.96) | 0.77 (0.65-0.92) | 0.66 (0.55-0.79) | 0.63 (0.53-0.75) | <.001 | .006 |
| HR (95% CI)c | 1 (referent) | 0.78 (0.54-1.11) | 0.60 (0.42-0.86) | 0.67 (0.47-0.95) | 0.63 (0.45-0.90) | 0.39 (0.27-0.57) | 0.66 (0.47-0.93) | 0.59 (0.41-0.83) | 0.43 (0.30-0.61) | 0.39 (0.27-0.56) | ||
| Total bilirubin (TBIL) | ||||||||||||
| Median, range | 5 (1-5) | 6 (5-6) | 6 (6-7) | 7 (7-7) | 8 (7-8) | 8 (8-9) | 9 (9-10) | 10 (10-11) | 12 (11-14) | 17 (14-29) | ||
| CRC cases | 262 | 271 | 260 | 277 | 252 | 249 | 244 | 292 | 275 | 280 | ||
| Person-years | 373 312 | 369 845 | 370 116 | 372 260 | 371 937 | 370 067 | 372 012 | 370 986 | 371 003 | 369 849 | ||
| HR (95% CI)a | 1 (referent) | 0.94 (0.80-1.12) | 0.87 (0.73-1.03) | 0.88 (0.75-1.05) | 0.78 (0.66-0.93) | 0.76 (0.64-0.90) | 0.72 (0.60-0.86) | 0.84 (0.71-1.00) | 0.78 (0.66-0.93) | 0.81 (0.68-0.96) | <.001 | <.001 |
| HR (95% CI)b | 1 (referent) | 0.95 (0.80-1.13) | 0.88 (0.74-1.05) | 0.90 (0.76-1.07) | 0.80 (0.67-0.96) | 0.78 (0.66-0.93) | 0.74 (0.62-0.89) | 0.88 (0.74-1.04) | 0.82 (0.68-0.97) | 0.85 (0.72-1.02) | .009 | .005 |
| HR (95% CI)c | 1 (referent) | 0.94 (0.74-1.18) | 0.84 (0.67-1.06) | 0.87 (0.69-1.10) | 0.74 (0.58-0.94) | 0.72 (0.56-0.91) | 0.67 (0.52-0.85) | 0.83 (0.66-1.06) | 0.76 (0.60-0.96) | 0.81 (0.64-1.02) | ||
| Gamma glutamyltransferase (GGT) | ||||||||||||
| Median, range | 13 (5-14) | 16 (15-17) | 18 (17-20) | 21 (20-23) | 24 (23-26) | 28 (26-30) | 33 (30-36) | 40 (36-45) | 51 (45-61) | 81 (62-156) | ||
| CRC cases | 210 | 230 | 237 | 265 | 263 | 283 | 270 | 276 | 311 | 317 | ||
| Person-years | 373 437 | 371 351 | 367 445 | 376 377 | 375 704 | 370 005 | 365 199 | 372 628 | 369 916 | 369 324 | ||
| HR (95% CI)a | 1 (referent) | 0.90 (0.75-1.09) | 0.83 (0.69-1.00) | 0.84 (0.70-1.01) | 0.80 (0.66-0.96) | 0.84 (0.70-1.01) | 0.80 (0.66-0.96) | 0.78 (0.65-0.94) | 0.89 (0.74-1.07) | 0.92 (0.77-1.10) | .02 | .01 |
| HR (95% CI)b | 1 (referent) | 0.88 (0.73-1.06) | 0.79 (0.65-0.95) | 0.77 (0.64-0.93) | 0.72 (0.60-0.86) | 0.73 (0.61-0.88) | 0.68 (0.57-0.83) | 0.66 (0.54-0.80) | 0.73 (0.61-0.88) | 0.74 (0.61-0.89) | <.001 | <.001 |
| HR (95% CI)c | 1 (referent) | 0.81 (0.60-1.10) | 0.68 (0.50-0.92) | 0.66 (0.49-0.89) | 0.58 (0.43-0.79) | 0.60 (0.45-0.82) | 0.54 (0.40-0.73) | 0.51 (0.37-0.69) | 0.60 (0.44-0.82) | 0.61 (0.45-0.83) | ||
| Alkaline phosphatase (ALP) | ||||||||||||
| Median, range | 51 (8-57) | 61 (57-64) | 67 (64-70) | 72 (70-75) | 77 (75-80) | 82 (80-85) | 88 (85-91) | 95 (91-99) | 104 (99-111) | 123 (111-203) | ||
| CRC cases | 229 | 229 | 245 | 267 | 273 | 279 | 244 | 284 | 279 | 333 | ||
| Person-years | 374 450 | 369 322 | 377 155 | 370 160 | 372 390 | 373 161 | 368 137 | 371 365 | 367 922 | 367 326 | ||
| HR (95% CI)a | 1 (referent) | 0.88 (0.73-1.06) | 0.86 (0.72-1.03) | 0.93 (0.78-1.11) | 0.91 (0.77-1.09) | 0.92 (0.77-1.10) | 0.81 (0.68-0.97) | 0.92 (0.78-1.10) | 0.92 (0.77-1.09) | 1.09 (0.92-1.29) | .13 | .24 |
| HR (95% CI)b | 1 (referent) | 0.88 (0.73-1.06) | 0.85 (0.71-1.02) | 0.92 (0.77-1.10) | 0.89 (0.75-1.07) | 0.90 (0.76-1.08) | 0.79 (0.66-0.94) | 0.89 (0.75-1.07) | 0.88 (0.74-1.05) | 1.03 (0.87-1.23) | .32 | .21 |
| HR (95% CI)c | 1 (referent) | 0.84 (0.66-1.08) | 0.81 (0.64-1.03) | 0.89 (0.71-1.13) | 0.86 (0.68-1.09) | 0.87 (0.69-1.10) | 0.73 (0.57-0.93) | 0.86 (0.68-1.09) | 0.84 (0.66-1.07) | 1.04 (0.83-1.31) | ||
| Total protein (TP) | ||||||||||||
| Median, range | 66 (52-68) | 68 (68-69) | 70 (69-70) | 71 (70-71) | 72 (71-72) | 73 (72-73) | 74 (73-74) | 75 (74-76) | 77 (76-78) | 79 (78-94) | ||
| CRC cases | 330 | 316 | 265 | 293 | 265 | 264 | 242 | 230 | 249 | 208 | ||
| Person-years | 372 915 | 373 768 | 375 479 | 372 382 | 371 427 | 372 497 | 370 049 | 369 884 | 367 311 | 365 674 | ||
| HR (95% CI)a | 1 (referent) | 0.97 (0.83-1.13) | 0.82 (0.70-0.97) | 0.93 (0.80-1.09) | 0.85 (0.72-1.00) | 0.86 (0.73-1.01) | 0.80 (0.68-0.94) | 0.77 (0.65-0.91) | 0.85 (0.72-1.00) | 0.72 (0.61-0.86) | <.001 | .56 |
| HR (95% CI)b | 1 (referent) | 0.96 (0.82-1.12) | 0.82 (0.69-0.96) | 0.92 (0.79-1.08) | 0.84 (0.71-0.99) | 0.84 (0.72-0.99) | 0.78 (0.66-0.92) | 0.75 (0.64-0.89) | 0.83 (0.70-0.98) | 0.70 (0.59-0.84) | <.001 | 0.52 |
| HR (95% CI) c | 1 (referent) | 0.92 (0.68-1.26) | 0.67 (0.48-0.92) | 0.85 (0.62-1.16) | 0.70 (0.51-0.97) | 0.71 (0.51-0.98) | 0.61 (0.44-0.85) | 0.57 (0.40-0.79) | 0.69 (0.49-0.95) | 0.50 (0.35-0.70) | ||
| Albumin (ALB) | ||||||||||||
| Median, range | 41 (32-42) | 43 (42-43) | 44 (43-44) | 44 (44-45) | 45 (45-45) | 46 (45-46) | 46 (46-47) | 47 (47-47) | 48 (47-49) | 50 (49-59) | ||
| CRC cases | 358 | 293 | 302 | 288 | 264 | 293 | 236 | 214 | 229 | 185 | ||
| Person-years | 368 321 | 372 990 | 370 112 | 374 749 | 367 819 | 373 629 | 375 104 | 368 838 | 371 268 | 368 556 | ||
| HR (95% CI)a | 1 (referent) | 0.82 (0.70-0.95) | 0.85 (0.73-0.99) | 0.82 (0.71-0.96) | 0.78 (0.67-0.92) | 0.87 (0.75-1.02) | 0.70 (0.60-0.83) | 0.67 (0.56-0.79) | 0.73 (0.62-0.86) | 0.63 (0.53-0.76) | <.001 | .87 |
| HR (95% CI)b | 1 (referent) | 0.83 (0.71-0.97) | 0.86 (0.74-1.01) | 0.84 (0.72-0.99) | 0.80 (0.68-0.94) | 0.90 (0.77-1.05) | 0.72 (0.61-0.86) | 0.69 (0.58-0.82) | 0.76 (0.64-0.89) | 0.66 (0.55-0.79) | <.001 | .84 |
| HR (95% CI)c | 1 (referent) | 0.67 (0.49-0.93) | 0.74 (0.53-1.02) | 0.70 (0.51-0.97) | 0.63 (0.45-0.88) | 0.79 (0.57-1.10) | 0.51 (0.36-0.72) | 0.46 (0.32-0.66) | 0.56 (0.39-0.79) | 0.42 (0.28-0.61) | ||
Abbreviations: CI, confidence interval; CRC, colorectal cancer; HR, hazard ratio.
Model 1: Estimated from the Cox regression model with age as the underlying time scale and adjusted for sex, race (white, non-white, unknown), fasting status and age at recruitment.
Model 2: Further adjusted for 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).
Recalibrated multivariable estimates accounting for dilution bias using the intraclass correlation coefficients calculated in the subsample of participants with repeat measurements of circulating liver function markers.