Serum Total Bilirubin and Risk of Cancer: A Swedish Cohort Study and Meta-Analysis

Monroy‐Iglesias, Maria J.; Moss, Charlotte; Beckmann, Kerri; Hammar, Niklas; Walldius, Göran; Bosco, Cecilia; Hemelrijck, Mieke Van; Santaolalla, Aida

doi:10.3390/cancers13215540

Cited by 11 publications

(13 citation statements)

References 33 publications

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“…bilirubin and lung cancer risk (HR Q4 vs.Q1 = 0.50, 95% CI: 0.44-0.59) (17): this study showed that higher serum total bilirubin levels decreased the risk of lung cancer among non-smokers (HR=0.45, 95% CI: 0.24-0.86) but not among smokers (HR=0.84, 95% CI: 0.44-1.60). In addition, a meta-analysis of five cohort studies reported that high levels of bilirubin were associated with decreased risk of lung cancer (relative risk=0.69, 95% CI: 0.55-0.86) (17).…”

Section: Discussionmentioning

confidence: 55%

“…A Japanese study using electronic medical records during a median 4.7-year follow-up demonstrated that serum bilirubin levels over 1.2 mg/dL were associated with a reduced risk of lung cancer among men (HR=0.47, 95% CI: 0.27-0.83) compared with ≤1.2 mg/dL ( 10 ). A large-scale study from Sweden also reported an inverse association between serum total bilirubin and lung cancer risk (HR Q4 vs.Q1 = 0.50, 95% CI: 0.44-0.59) ( 17 ): this study showed that higher serum total bilirubin levels decreased the risk of lung cancer among non-smokers (HR=0.45, 95% CI: 0.24-0.86) but not among smokers (HR=0.84, 95% CI: 0.44-1.60). In addition, a meta-analysis of five cohort studies reported that high levels of bilirubin were associated with decreased risk of lung cancer (relative risk=0.69, 95% CI: 0.55-0.86) ( 17 ).…”

Section: Discussionmentioning

confidence: 98%

“…A large-scale study from Sweden also reported an inverse association between serum total bilirubin and lung cancer risk (HR Q4 vs.Q1 = 0.50, 95% CI: 0.44-0.59) ( 17 ): this study showed that higher serum total bilirubin levels decreased the risk of lung cancer among non-smokers (HR=0.45, 95% CI: 0.24-0.86) but not among smokers (HR=0.84, 95% CI: 0.44-1.60). In addition, a meta-analysis of five cohort studies reported that high levels of bilirubin were associated with decreased risk of lung cancer (relative risk=0.69, 95% CI: 0.55-0.86) ( 17 ). A study from the UK Biobank reported a potential causal association between serum bilirubin and the incidence of lung cancer by Mendelian Randomization ( 21 ); this study suggested that genetically predicted serum bilirubin might protect individuals from exposure hazards to high levels of oxidants associated with cigarette smoking.…”

Section: Discussionmentioning

confidence: 98%

“…Bilirubin is produced as a byproduct of heme degradation and mostly transported in blood tightly bound to albumin, but a very small fraction of bilirubin remains unbound, i.e., free bilirubin, which has biological effects (11,12). Several prospective studies investigating the associations of total bilirubin and albumin levels with lung cancer risk have been conducted (13)(14)(15)(16), and a meta-analysis indicated an inverse association between total bilirubin levels and risk of lung cancer (17). However, this epidemiological evidence came mainly from studies conducted among European and Asian descendants.…”

Section: Introductionmentioning

confidence: 99%

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Associations of Pre-Diagnostic Serum Levels of Total Bilirubin and Albumin With Lung Cancer Risk: Results From the Southern Community Cohort Study

et al. 2022

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BackgroundPrevious studies conducted among European and Asian decedents reported inverse associations of serum total bilirubin and albumin with lung cancer risk. Yet, no study has been conducted among African Americans or low-income European Americans.MethodsThis study included 522 incident lung cancer cases and 979 matched controls nested in the Southern Community Cohort Study, a cohort of predominantly low-income African and European Americans. Serum levels of total bilirubin and albumin, collected up to 11 years prior to case diagnoses, were measured by a clinical chemistry analyzer. Conditional logistic regression models were applied to evaluate the associations of total bilirubin and albumin with lung cancer risk.ResultsOverall, serum levels of total bilirubin (ORT3 vs. T1 = 0.96, 95% CI: 0.66-1.39) were not significantly associated with lung cancer risk. However, higher levels of serum total bilirubin were significantly associated with decreased risk of lung cancer among participants who were diagnosed within two years following sample collection (ORT3 vs. T1 = 0.36, 95% CI: 0.15-0.87) and among former/never smokers (ORT3 vs. T1 = 0.54, 95% CI: 0.32-0.93). Serum levels of albumin were significantly associated with decreased risk of lung cancer overall (ORT3 vs. T1 = 0.70, 95% CI: 0.50-0.98) and among African Americans (ORT3 vs. T1 = 0.62, 95% CI: 0.41-0.96), but not among European Americans.ConclusionOur results indicate that in a low-income African American and European American population, serum levels of total bilirubin may be related to lung cancer progression and differ by smoking status. Meanwhile, the association of serum albumin levels with lung cancer risk may differ by race. Further studies are warranted to confirm these results.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Associations of Pre-Diagnostic Serum Levels of Total Bilirubin and Albumin With Lung Cancer Risk: Results From the Southern Community Cohort Study

et al. 2022

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“…Interestingly, epidemiological observations revealed an inverse correlation of serum bilirubin levels and CRC risk [58][59][60]. However, there are also conflicting reports showing that the relationship of bilirubin and CRC risk may be sex-dependent [61,62].…”

Section: The Bile Pigment Bilirubin and Its Effects On Colorectal Can...mentioning

confidence: 99%

Bile acids, bile pigments and colorectal cancer risk

Kuhls

Osswald

Ocvirk

2022

Current Opinion in Gastroenterology

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Purpose of reviewThe gut microbial co-metabolism of bile-derived compounds (e.g. bile acids and bile pigments) affects colorectal cancer (CRC) risk. Here, we review recent findings with focus on selected novel aspects of bileassociated effects with interesting but unclear implications on CRC risk. Recent findingsNumerous studies demonstrated novel biotransformation of bile acids by gut bacteria (e.g. microbial conjugation of bile acids), resulting in diverse bile acid compounds that show complex interactions with host receptors (e.g. FXR, TGR5). In addition, YAP-associated signalling in intestinal epithelial cells is modulated via bile acid receptor TGR5 and contributes to colonic tumorigenesis. Finally, studies indicate that serum levels of the bile pigment bilirubin are inversely associated with CRC risk or intestinal inflammation and that bilirubin affects gut microbiota composition.

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Interplay Of Serum Bilirubin and Tobacco Smoking with Lung and Head and Neck Cancers in a Diverse, EHR-linked Los Angeles Biobank

Venkateswaran,

Petter,

Boulier

et al. 2023

Preprint

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Structured AbstractBackgroundBilirubin is a potent antioxidant with a protective role in many diseases. We examined the relationships between serum bilirubin (SB) levels, tobacco smoking (a known cause of low SB), and aerodigestive cancers, grouped as lung (LC) and head and neck (HNC).MethodsWe examined the associations between SB, LC and HNC using data from 393,210 participants from UCLA Health, employing regression models, propensity score matching, and polygenic scores.ResultsCurrent tobacco smokers showed lower SB (-0.04mg/dL, 95% CI: [-0.04, -0.03]), compared to never-smokers. Lower SB levels were observed in HNC and LC cases (-0.10 mg/dL, [-0.13, -0.09] and -0.09 mg/dL, CI [-0.1, -0.07] respectively) compared to cancer-free controls with the effect persisting after adjusting for smoking. SB levels were inversely associated with HNC and LC risk (ORs per SD change in SB: 0.64, CI [0.59,0.69] and 0.57, CI [0.43,0.75], respectively). Lastly, a polygenic score (PGS) for SB was associated with LC (OR per SD change of SB-PGS: 0.71, CI [0.67, 0.76]).ConclusionsLow SB levels are associated with an increased risk of both HNC and LC, independent of the effect of tobacco smoking with tobacco smoking demonstrating a strong interaction with SB on LC risk. Additionally, genetically predicted low SB (from polygenic scores) is negatively associated with LC.ImpactThese findings suggest that SB could serve as a potential early biomarker for LC and HNC.

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Serum Total Bilirubin and Risk of Cancer: A Swedish Cohort Study and Meta-Analysis

Cited by 11 publications

References 33 publications

Associations of Pre-Diagnostic Serum Levels of Total Bilirubin and Albumin With Lung Cancer Risk: Results From the Southern Community Cohort Study

Associations of Pre-Diagnostic Serum Levels of Total Bilirubin and Albumin With Lung Cancer Risk: Results From the Southern Community Cohort Study

Bile acids, bile pigments and colorectal cancer risk

Interplay Of Serum Bilirubin and Tobacco Smoking with Lung and Head and Neck Cancers in a Diverse, EHR-linked Los Angeles Biobank

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