Background

Bilirubin is a by-product of haemoglobin degradation with strong antioxidant properties. It has been hypothesized to be preventive against the development of cancer. However, studies published to date have shown inconclusive results among different cancer types and overall cancer. We therefore 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. Moreover, we also performed a systematic review and meta-analysis for specific cancer types (colorectal, breast and lung).

Method

Our study cohort included 137,045 cancer-free men and women, aged >20 years, with baseline measurements of STB followed 1985-2011 in the Swedish National Cancer and Cause of Death Registers. Cox proportional hazards regression was used to analyse associations between STB and site-specific cancer (upper gastrointestinal, colorectal, lung, breast, gynaecological, prostate, bladder, melanoma, and haematological), and overall cancer risk. The meta-analysis included 3 studies in colorectal, 2 in breast and 2 in lung cancer.

Results

A total of 27,695 participants developed cancer during a follow-up time of 19 years. We found no association between high levels of STB and risk of overall cancer (Hazard Ratio (HR) for the 4^th quartile (Q4): 0.96; 95% Confidence Interval (CI): 0.99-1.00), as compared to the 1st quartile (Q1). When stratifying by sex, no statistically significant associations were found. There was an inverse association between increased STB and risk of lung cancer (HR for Q4 vs. Q1: 0.50; 95%CI 0.44-0.59). No clear associations were found between STB level and other cancer types. The meta-analysis showed a borderline inverse association between high levels of STB and risk of lung cancer (Relative risk (RR): 0.65; 95%CI: 0.40-1.05). No associations were seen for colorectal and breast cancer risk.

Conclusion

Overall high levels of STB had no association with overall cancer risk. However, an inverse association was found between high levels of STB and risk of lung cancer. This association was consistent with the results of our meta-analysis. Further insights into the association between STB and lung cancer risk are needed to establish the potential protective effect of STB.

Impact statement

High STB levels may be protective against lung cancer.