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

Maria J Monroy-Iglesias,Niklas Hammar,Charlotte Moss,Kerri Beckmann,Aida Santaolalla,Mieke Van Hemelrijck,Cecilia Bosco,Goran Walldius

doi:10.3390/cancers13215540

Maria J Monroy-Iglesias, Niklas Hammar + Show 6 more

Open Access

https://doi.org/10.3390/cancers13215540

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Abstract

Simple SummarySeveral studies published to date have shown inconclusive results in the association between serum bilirubin and risk of site-specific cancer types and overall cancer. Therefore, there is a need to further investigate this association. Data from the large Swedish Apolipoprotein Mortality Risk (AMORIS) cohort study was used. We found that overall high levels of bilirubin had no association with overall cancer risk. However, a positive association was found between melanoma and breast cancer risk. On the other hand, an inverse association was found between high levels of bilirubin and risk of gynecological and lung cancers. Further studies are required to establish if bilirubin can be used as a biomarker for risk assessment and/or as a novel therapeutic target.Bilirubin has strong antioxidant properties that have been hypothesized to be preventive against the development of cancer. Thus, we aimed to investigate the association between serum total bilirubin (STB) and risk of overall and site-specific cancers in the large Swedish Apolipoprotein Mortality Risk (AMORIS) cohort. We also performed a systematic review and meta-analysis for specific cancer types (colorectal, breast and lung). We found no association between high levels of STB and risk of overall cancer. Regarding site-specific cancer, there was an inverse association between increased STB and lung cancer (Hazard Ratio (HR) for the 4th quartile (Q4) vs. Q1: 0.50; 95%CI: 0.44–0.59) and gynecological cancer (HR for Q4 vs. Q1: 0.86; 95%CI: 0.76–0.99). A positive association was found with melanoma (HR for Q4 vs. Q1: 1.25; 95%CI: 1.06–1.47) and breast cancer (HR for Q4 vs. Q1: 1.13; 95%CI: 1.01–1.25) risk. The meta-analysis showed an inverse association between high levels of STB and risk of lung cancer (Relative risk (RR): 0.69; 95%CI: 0.55–0.86). No associations were seen for colorectal and breast cancer risk. Further studies are required to establish if bilirubin can be used as a biomarker for risk assessment and/or as a novel therapeutic target.

Highlights

It has been proposed that endogenous bile pigments, such as bilirubin, may play a protective role against the development of a variety of chronic diseases, including cancer, due to their potent anti-inflammatory and antioxidant properties [1]
Our findings suggest no association between Serum total bilirubin (STB) levels and risk of overall cancer
A consistent inverse association was found between high levels of STB and risk of lung and gynecological cancer

Summary

Introduction

It has been proposed that endogenous bile pigments, such as bilirubin, may play a protective role against the development of a variety of chronic diseases, including cancer, due to their potent anti-inflammatory and antioxidant properties [1]. Serum total bilirubin (STB) is derived primarily from the degradation of hemoglobin and transported to the liver by binding to albumin [1]. Blood levels of total bilirubin consist of primarily unconjugated bilirubin (UCB). UCB has been found to be the most active antioxidant component of bilirubin [2,3]. After the liver removes UCB from the blood, it is conjugated by a uridine diphosphoglucuronyltransferase (UGT1A1) and transported to the bowel via the bile.

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