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.
Serum cardiometabolic and liver function markers in relation to colorectal cancer risk and survival
Colorectal cancer is the third most common cancer and the second leading cause of cancer death in the world. It shared several metabolic risk factors with cardiovascular disease and type 2 diabetes. Despite the link, it remains be established how markers of cardiometabolic conditions are associated with the onset and outcome of colorectal cancer. Another interesting link is between liver disease and colorectal cancer. Patients with chronic liver diseases have been demonstrated to be more likely to develop colorectal cancer. Also, most patients with advanced colorectal cancer die from distant spread into the liver. Recent studies on the gut bacteria have shown a potential relationship between liver-derived metabolites and colorectal cancer mediated through bacterial actions. These data all indicate the importance of better understanding the role of liver function in colorectal cancer. Therefore, in this study, we aim to provide a comprehensive assessment of cardiometabolic biomarkes and liver function tests in relation to colorectal cancer using the soon-to-be released serum biochemistry marker data.
|Lead investigator:||Dr Mingyang Song|
|Lead institution:||Harvard School of Public Health|
1 related Return
|Return ID||App ID||Description||Archive Date|
|3731||46466||Serum lipid profiles and risk of colorectal cancer: a prospective cohort study in the UK Biobank||5 Aug 2021|