Genetic variants of MUC4 are associated with prevalence and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels

Abstract As a disease with high mortality and prevalence rates worldwide, colorectal cancer (CRC) has been thoroughly investigated. Mucins are involved in the induction of CRC and regulation of intestinal homeostasis. However, the role of MUC4, which is a member of the mucin gene family, is controversial because it shows an association with either decreased susceptibility to or a worse prognosis of CRC. In our study, the multifunctional aspects of MUC4 were elucidated by genetic polymorphism analysis in a case-control study of 420 controls and 464 CRC patients. The MUC4 rs1104760 A>G polymorphism had a protective effect on CRC risk (AG, AOR = 0.537; GG, AOR = 0.297; dominant model, AOR = 0.493; recessive model, AOR = 0.382). In addition, the MUC4 rs2688513 was associated with an increased mortality rate of CRC (5 years, GG, adjusted HR = 6.496; recessive model, adjusted HR = 5.848). Furthermore, a significant synergistic effect was observed between MUC4 rs1104760 A>G and low-density lipoprotein cholesterol (LDL-C) indicating a high potential as a biomarker for CRC susceptibility. This is the first study to indicate a significant association between MUC4 genetic polymorphisms and CRC prevalence, suggesting a functional genetic variant with the LDL-C level, for CRC prevention.