Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels.
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 bee...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287768&type=printable |
| _version_ | 1797394454302162944 |
|---|---|
| author | Min Jung Kwon Jeong Yong Lee Eo Jin Kim Eun Ju Ko Chang Soo Ryu Hye Jung Cho Hak Hoon Jun Jong Woo Kim Nam Keun Kim |
| author_facet | Min Jung Kwon Jeong Yong Lee Eo Jin Kim Eun Ju Ko Chang Soo Ryu Hye Jung Cho Hak Hoon Jun Jong Woo Kim Nam Keun Kim |
| author_sort | Min Jung Kwon |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T00:19:59Z |
| format | Article |
| id | doaj.art-0e41061786574081894eb4dec6767c3b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-09T00:19:59Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-0e41061786574081894eb4dec6767c3b2023-12-12T05:35:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01186e028776810.1371/journal.pone.0287768Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels.Min Jung KwonJeong Yong LeeEo Jin KimEun Ju KoChang Soo RyuHye Jung ChoHak Hoon JunJong Woo KimNam Keun KimAs 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287768&type=printable |
| spellingShingle | Min Jung Kwon Jeong Yong Lee Eo Jin Kim Eun Ju Ko Chang Soo Ryu Hye Jung Cho Hak Hoon Jun Jong Woo Kim Nam Keun Kim Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels. PLoS ONE |
| title | Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels. |
| title_full | Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels. |
| title_fullStr | Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels. |
| title_full_unstemmed | Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels. |
| title_short | Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels. |
| title_sort | genetic variants of muc4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with ldl c levels |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0287768&type=printable |
| work_keys_str_mv | AT minjungkwon geneticvariantsofmuc4areassociatedwithsusceptibilitytoandmortalityofcolorectalcancerandexhibitsynergisticeffectswithldlclevels AT jeongyonglee geneticvariantsofmuc4areassociatedwithsusceptibilitytoandmortalityofcolorectalcancerandexhibitsynergisticeffectswithldlclevels AT eojinkim geneticvariantsofmuc4areassociatedwithsusceptibilitytoandmortalityofcolorectalcancerandexhibitsynergisticeffectswithldlclevels AT eunjuko geneticvariantsofmuc4areassociatedwithsusceptibilitytoandmortalityofcolorectalcancerandexhibitsynergisticeffectswithldlclevels AT changsooryu geneticvariantsofmuc4areassociatedwithsusceptibilitytoandmortalityofcolorectalcancerandexhibitsynergisticeffectswithldlclevels AT hyejungcho geneticvariantsofmuc4areassociatedwithsusceptibilitytoandmortalityofcolorectalcancerandexhibitsynergisticeffectswithldlclevels AT hakhoonjun geneticvariantsofmuc4areassociatedwithsusceptibilitytoandmortalityofcolorectalcancerandexhibitsynergisticeffectswithldlclevels AT jongwookim geneticvariantsofmuc4areassociatedwithsusceptibilitytoandmortalityofcolorectalcancerandexhibitsynergisticeffectswithldlclevels AT namkeunkim geneticvariantsofmuc4areassociatedwithsusceptibilitytoandmortalityofcolorectalcancerandexhibitsynergisticeffectswithldlclevels |