Mechanisms
Colorectal cancer patients have higher CETP activity and lower LCAT and PON-1 activity, with CETP mass an independent risk predictor (Clin Biochem 2019)
Original title: Changes in lecithin: cholesterol acyltransferase, cholesteryl ester transfer protein and paraoxonase-1 activities in patients with colorectal cancer
Low HDL cholesterol has been linked to colorectal cancer (CRC) risk, and this study measured the activities of the HDL-shaping enzymes LCAT and CETP, plus the HDL-antioxidant enzyme paraoxonase-1 (PON-1), in ninety-nine CRC patients and 101 healthy controls. CRC patients had lower HDL-C (P < .001), lower LCAT activity (P < .050), higher CETP activity (P < .050), and lower PON-1 paraoxonase and arylesterase activities (P < .050 and P < .001). Univariate logistic regression identified HDL-C level, CETP activity (odds ratio 1.010, P < .01) and CETP mass (odds ratio 0.994, P < .001) as candidate markers of elevated CRC risk, with CETP mass remaining a significant predictor after adjusting for traditional risk factors and oxidative stress (odds ratio 0.993 and 0.982). The authors conclude altered CETP, LCAT and PON-1 activity and HDL structure may play a role in colorectal carcinogenesis, a preliminary human finding in a novel oncology application of CETP biology.
Original abstract
Background: Previous studies revealed decreased level of high-density lipoprotein cholesterol (HDLC) as important factor for development of colorectal cancer (CRC). Quantity and structure of HDL particles depend on activities of lipid transfer proteins lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP), but this topic is largely unexplored in CRC. The main objective of this study was to investigate activities of LCAT and CETP in patients with CRC. Additionally, we analyzed activity of paraoxonase-1 (PON-1), as a main carrier of HDL-antioxidant function.
Materials And Methods: Ninety-nine CRC patients and 101 healthy individuals were included. LCAT and CETP activities were assessed by measuring rates of formation and transfer of cholesteryl esters. PON-1 paraoxonase and arylesterase activities were measured.
Results: Lower levels of HDL-C (p < .001) were observed in cohort of patients, alongside with decreased LCAT (p < .050) and increased CETP activity (p < .050). Both PON-1 activities were diminished in CRC (p < .050 and p < .001 respectively). Univariate logistic regression singled out HDL-C level (OR = 0.218, p < .001), CETP activity (OR = 1.010, p < .01) and mass (OR = 0.994, p < .001) as possible markers of elevated CRC risk. CETP mass maintained its predictive significance when adjusted for traditional risk factors and level of oxidative stress (OR = 0.993, p < .001; OR = 0.982, p < .050, respectively).
Conclusion: Our results demonstrated increased CETP and decreased LCAT and PON-1 activities in CRC patients. In preliminary analysis CETP mass was identified as potential significant predictor of CRC development, suggesting that alterations in HDL-C levels, alongside with changes in HDL structure might have a role in carcinogenesis.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.