Associations between Prediagnostic Circulating Bilirubin Levels and Risk of Gastrointestinal Cancers in the UK Biobank
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Study Population
2.2. Blood Collection and Laboratory Methods
2.3. Follow-Up and Outcomes
2.4. Statistical Analysis
3. Results
3.1. General Characteristics of the Study Population
3.2. Associations between Total Bilirubin Levels and Risk of GI Cancers
3.3. Subgroup and Sensitivity Analyses
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Log-Total Bilirubin Tertile (μM/L) | ||||||
Baseline Characteristic | Men | Women | ||||
1 (1.43–7.94) | 2 (7.95–10.64) | 3 (10.65–144.52) | 1 (1.08–6.36) | 2 (6.37–8.41) | 3 (8.42–115.75) | |
Cases (N) | ||||||
Colorectal cancer | 614 | 555 | 562 | 462 | 428 | 381 |
Colon cancer | 370 | 352 | 336 | 342 | 302 | 287 |
Rectal cancer | 244 | 203 | 226 | 120 | 126 | 94 |
Esophageal adenocarcinoma | 124 | 86 | 81 | 21 | 16 | 10 |
Esophageal squamous-cell carcinoma | 31 | 15 | 13 | 24 | 21 | 20 |
Stomach cardia cancer | 41 | 40 | 32 | 10 | 11 | 5 |
Stomach non-cardia cancer | 18 | 22 | 16 | 16 | 11 | 9 |
Oral cancer | 126 | 111 | 110 | 60 | 60 | 57 |
Pancreatic cancer | 110 | 118 | 77 | 76 | 98 | 80 |
Hepatocellular carcinoma | 15 | 35 | 60 | 3 | 7 | 15 |
Intrahepatic bile duct cancer | 17 | 14 | 23 | 23 | 18 | 25 |
Age at recruitment (years) ° | 56.3 (8.1) | 56.7 (8.1) | 56.6 (8.3) | 56.1 (7.9) | 56.6 (7.9) | 55.7 (8.2) |
Body mass index (kg/m2) ° | 28.2 (4.5) | 27.8 (4.1) | 27.5 (4.0) | 27.9 (5.4) | 27.0 (5.1) | 26.3 (4.9) |
Waist circumference (cm) ° | 97.9 (11.8) | 96.8 (11.1) | 95.9 (10.9) | 86.7 (12.9) | 84.4 (12.3) | 82.7 (12.0) |
Height (cm) ° | 174.9 (6.8) | 175.8 (6.8) | 176.2 (6.9) | 161.8 (6.3) | 162.5 (6.3) | 163.1 (6.3) |
Smoking status (%) | ||||||
Never | 30 | 34 | 36 | 32 | 33 | 34 |
Former | 33 | 34 | 33 | 32 | 34 | 34 |
Current | 49 | 29 | 21 | 46 | 31 | 23 |
Alcohol consumption status (%) | ||||||
Never | 39 | 30 | 31 | 40 | 32 | 28 |
Former | 41 | 30 | 29 | 43 | 31 | 26 |
Current | 33 | 34 | 34 | 33 | 34 | 34 |
Physical activity (MET§ hour/week) (%) | ||||||
<10 | 36 | 33 | 31 | 36 | 33 | 31 |
>60 | 34 | 33 | 33 | 31 | 34 | 35 |
Education (%) | ||||||
College/university degree | 31 | 33 | 36 | 30 | 33 | 36 |
Family history of CRC (%) | ||||||
Yes | 33 | 34 | 34 | 33 | 34 | 33 |
Prevalent diabetes (%) | ||||||
Yes | 41 | 30 | 29 | 42 | 30 | 28 |
Aspirin/Ibuprofen Use (%) | ||||||
Yes | 34 | 33 | 33 | 35 | 33 | 32 |
Red and processed meat (%) | ||||||
<2/week | 31 | 34 | 35 | 32 | 33 | 34 |
≥4/week | 35 | 33 | 32 | 35 | 33 | 32 |
Ever use of hormone therapy (%) ¤ | ||||||
Yes | 35 | 34 | 31 |
Both Sexes | Men | Women | |
---|---|---|---|
Colorectal Cancer (CRC) | |||
N cases | 3002 | 1731 | 1271 |
Crude HR (95%CI) * | 0.93 (0.87–1.00) | 0.92 (0.85–1.01) | 0.96 (0.86–1.06) |
p | 0.05 | 0.07 | 0.39 |
HR (95%CI) ** | 0.95 (0.88–1.02) | 0.93 (0.85–1.02) | 0.98 (0.88–1.09) |
p | 0.14 | 0.11 | 0.74 |
Pnon-linearity | 0.02 | N/A | N/A |
Colon Cancer | |||
N cases | 1989 | 1058 | 931 |
Crude HR (95%CI) * | 0.93 (0.85–1.01) | 0.91 (081–1.01) | 0.96 (0.85–1.08) |
p | 0.08 | 0.08 | 0.49 |
HR (95%CI) ** | 0.95 (0.87–1.04) | 0.92 (0.82–1.03) | 1.00 (0.88–1.13) |
p | 0.26 | 0.15 | >0.9 |
Pnon-linearity | 0.07 | N/A | N/A |
Rectal Cancer | |||
N cases | 1013 | 673 | 340 |
Crude HR (95%CI) * | 0.95 (0.84–1.07) | 0.95 (0.82–1.09) | 0.95 (0.78–1.16) |
p | 0.38 | 0.48 | 0.61 |
HR (95%CI) ** | 0.94 (0.83–1.07) | 0.93 (0.80–1.09) | 0.97 (0.77–1.21) |
p | 0.36 | 0.37 | 0.76 |
Pnon-linearity | 0.29 | N/A | N/A |
Esophageal Adenocarcinoma (EAC) | |||
N cases | 338 | 291 | 47 |
Crude HR (95%CI) * | 0.69 (0.55–0.87) | 0.72 (0.56–0.91) | 0.60 (0.33–1.10) |
p | 0.002 | 0.01 | 0.10 |
HR (95%CI) ** | 0.72 (0.56–0.92) | 0.74 (0.56–0.97) | 0.84 (0.40–1.78) |
p | 0.01 | 0.03 | 0.65 |
Pnon-linearity | 0.06 | N/A | N/A |
Esophageal Squamous-Cell Carcinoma (ESCC) | |||
N cases | 124 | 59 | 65 |
Crude HR (95%CI) * | 0.82 (0.55–1.21) | 0.77 (0.40–1.48) | 0.86 (0.55–1.35) |
p | 0.32 | 0.43 | 0.51 |
HR (95%CI) ** | 0.74 (0.44–1.24) | N/A | 0.68 (0.33–1.39) |
p | 0.25 | N/A | 0.29 |
Pnon-linearity | N/A | N/A | 0.11 |
Stomach Cardia Cancer | |||
N cases | 139 | 113 | 26 |
Crude HR (95%CI) * | 1.01 (0.71–1.45) | 1.14 (0.77–1.67) | 0.53 (0.20–1.43) |
p | 0.07 | 0.51 | 0.21 |
HR (95%CI) ** | 1.33 (0.84–2.11) | 1.59 (0.90–2.82) | N/A |
p | 0.23 | 0.11 | N/A |
Pnon-linearity | 0.86 | N/A | N/A |
Stomach Non-Cardia Cancer | |||
N cases | 92 | 56 | 36 |
Crude HR (95%CI) * | 0.67 (0.36–1.26) | 0.83 (0.37–1.87) | 0.56 (0.24–1.33) |
p | 0.22 | 0.66 | 0.19 |
HR (95%CI) ** | 0.88 (0.41–1.91) | 3.23 (0.44–23.61) | 0.15 (0.00–7.60) |
p | 0.74 | 0.25 | 0.34 |
Pnon-linearity | N/A | N/A | N/A |
Oral Cancer | |||
N cases | 524 | 347 | 177 |
Crude HR (95%CI) * | 0.89 (0.75–1.05) | 0.85 (0.69–1.06) | 0.96 (0.74–1.24) |
p | 0.17 | 0.14 | 0.75 |
HR (95%CI) ** | 0.93 (0.77–1.13) | 0.94 (0.73–1.20) | 1.01 (0.75–1.35) |
p | 0.46 | 0.61 | >0.9 |
Pnon-linearity | >0.9 | N/A | N/A |
Pancreatic Cancer | |||
N cases | 559 | 305 | 254 |
Crude HR (95%CI) * | 0.94 (0.81–1.09) | 0.87 (0.70–1.06) | 1.03 (0.84–1.25) |
p | 0.40 | 0.16 | 0.78 |
HR (95%CI) ** | 0.96 (0.82–1.13) | 0.83 (0.65–1.04) | 1.11 (0.89–1.38) |
p | 0.62 | 0.11 | 0.36 |
Pnon-linearity | N/A | N/A | N/A |
Hepatocellular Carcinoma (HCC) | |||
N cases | 135 | 110 | 25 |
Crude HR (95%CI) * | 1.65 (1.21–2.49) | 1.57 (1.08–2.29) | 1.69 (1.03–2.79) |
p | 0.002 | 0.02 | 0.04 |
HR (95%CI) ** | 2.07 (1.15–3.73) | 1.54 (0.62–3.27) | N/A |
p | 0.02 | 0.26 | N/A |
Pnon-linearity | 0.02 | N/A | N/A |
Intrahepatic Bile Duct (IBD) Cancer | |||
N cases | 120 | 54 | 66 |
Crude HR (95%CI) * | 1.37 (0.69–1.96) | 1.42 (0.86–2.36) | 1.29 (0.81–2.06) |
p | 0.08 | 0.17 | 0.29 |
HR (95%CI) ** | 1.67 (1.07–2.62) | 5.59 (0.88–35.75) | 1.40 (0.78–2.50) |
p | 0.03 | 0.07 | 0.25 |
Pnon-linearity | >0.9 | N/A | N/A |
Cancer Types | HR (95%CI) | p |
---|---|---|
Colorectal cancer (CRC) | ||
Both sexes | 1.03 (0.95–1.13) | 0.46 |
Men | 0.98 (0.88–1.10) | 0.73 |
Women | 1.13 (0.99–1.29) | 0.07 |
Colon cancer | ||
Both sexes | 1.07 (0.96–1.20) | 0.20 |
Men | 0.98 (0.85–1.14) | 0.80 |
Women | 1.21 (1.03–1.42) | 0.02 |
Rectal cancer | ||
Both sexes | 1.00 (0.85–1.17) | >0.90 |
Men | 1.02 (0.84–1.24) | 0.83 |
Women | 1.05 (0.79–1.40) | 0.73 |
Esophageal adenocarcinoma (EAC) | ||
Both sexes | 0.76 (0.56–1.03) | 0.07 |
Men | 0.76 (0.53–1.08) | 0.13 |
Women | 1.58 (0.55–4.53) | 0.40 |
Esophageal squamous-cell carcinoma (ESCC) | ||
Both sexes | 0.50 (0.22–1.13) | 0.10 |
Stomach cardia cancer | ||
Both sexes | 1.45 (0.77–2.73) | 0.25 |
Stomach non-cardia cancer | ||
Both sexes | 0.45 (0.15–1.36) | 0.16 |
Oral cancer | ||
Both sexes | 0.95 (0.75–1.21) | 0.68 |
Men | 0.92 (0.67–1.26) | 0.61 |
Women | 0.97 (0.65–1.47) | 0.90 |
Pancreatic cancer | ||
Both sexes | 0.97 (0.80–1.16) | 0.72 |
Men | 0.77 (0.58–1.02) | 0.07 |
Women | 1.19 (0.92–1.54) | 0.19 |
Hepatocellular carcinoma (HCC) | ||
Both sexes | 2.01 (1.10–3.68) | 0.02 |
Intrahepatic bile duct (IBD) cancer | ||
Both sexes | 1.36 (0.81–2.30) | 0.30 |
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Seyed Khoei, N.; Wagner, K.-H.; Carreras-Torres, R.; Gunter, M.J.; Murphy, N.; Freisling, H. Associations between Prediagnostic Circulating Bilirubin Levels and Risk of Gastrointestinal Cancers in the UK Biobank. Cancers 2021, 13, 2749. https://doi.org/10.3390/cancers13112749
Seyed Khoei N, Wagner K-H, Carreras-Torres R, Gunter MJ, Murphy N, Freisling H. Associations between Prediagnostic Circulating Bilirubin Levels and Risk of Gastrointestinal Cancers in the UK Biobank. Cancers. 2021; 13(11):2749. https://doi.org/10.3390/cancers13112749
Chicago/Turabian StyleSeyed Khoei, Nazlisadat, Karl-Heinz Wagner, Robert Carreras-Torres, Marc J. Gunter, Neil Murphy, and Heinz Freisling. 2021. "Associations between Prediagnostic Circulating Bilirubin Levels and Risk of Gastrointestinal Cancers in the UK Biobank" Cancers 13, no. 11: 2749. https://doi.org/10.3390/cancers13112749