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

• Published in: PloS one Vol. 18; no. 6; p. e0287768
• Main Authors: Kwon, Min Jung, Lee, Jeong Yong, Kim, Eo Jin, Ko, Eun Ju, Ryu, Chang Soo, Cho, Hye Jung, Jun, Hak Hoon, Kim, Jong Woo, Kim, Nam Keun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.06.2023; Public Library of Science (PLoS)
• Subjects: Age; Analysis; Biology and Life Sciences; Biomarkers; Body mass index; Cancer; Cancer therapies; Case-Control Studies; Cholesterol; Cholesterol, LDL; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Diabetes; Diagnosis; Disease; Disease susceptibility; Gene polymorphism; Genetic analysis; Genetic aspects; Genetic diversity; Genetic variance; Health aspects; High density lipoprotein; Homeostasis; Humans; Hypertension; Lipids; Low density lipoprotein; Medical prognosis; Medical screening; Medicine and Health Sciences; Metabolism; Mortality; Mucin; Mucin-4 - genetics; Mucins; Mucins - genetics; Polymorphism; Precision medicine; Software; Surgery; Survival analysis; Synergistic effect; Tumors; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0287768

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 the regulation of intestinal homeostasis but a member of the mucin gene family MUC4 has a controversial role in CRC. MUC4 has been associated 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. 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) and MUC4 rs2688513 A>G was associated with an increased mortality rate of CRC (5 years, GG, adjusted HR = 6.496; recessive model, adjusted HR = 5.848). In addition, MUC4 rs1104760 A>G showed a high probability of being a potential biomarker for CRC patients with low-density lipoprotein cholesterol (LDL-C) in the risk range while showing a significant synergistic effect with the LDL-C level. 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.