Abstract
Evidence links the liver to development of colorectal cancer (CRC). However, it remains unknown how liver function may influence CRC risk in the general population. We conducted a prospective cohort study in the UK Biobank of 375 693 participants who provided blood samples in 2006 to 2010. Circulating levels of liver function markers (alanine transaminase [ALT], aspartate transaminase [AST], total bilirubin [TBIL], gamma glutamyltransferase [GGT], alkaline phosphatase [ALP], total protein [TP] and albumin [ALB]) were measured. Incident cancer cases were identified through linkage to the national cancer registry up to 2019. Repeated biomarker measurements were available from a subset of 11 320 participants who were re-assessed in 2012 to 2013. After a median follow-up of 10.0 years, we documented 2662 cases of CRC. Circulating levels of ALT, AST, TBIL, GGT, TP and ALB at baseline were inversely associated with CRC risk (P < .01), with multivariable hazard ratio (95% confidence interval) comparing decile 10 vs 1 of 0.62 (0.51-0.75), 0.63 (0.53-0.75), 0.85 (0.72-1.02), 0.74 (0.61-0.89), 0.70 (0.59-0.84) and 0.66 (0.55-0.79), respectively. Strengthened associations were found after recalibration for repeated measurements. The associations appeared stronger for proximal colon cancer than distal colon cancer and rectal cancer, but consistent for early-, mid- and late-onset CRC. In a large cohort of general population, the UK Biobank, higher circulating levels of ALT, AST, TBIL, GGT, TP and ALB, largely within the normal range, were associated with a lower risk of CRC. The findings support a link between liver function and CRC, and may spur future research on the gut-microbiota-liver axis.</p>