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...
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| Veröffentlicht in: | PloS one 2023-06, Vol.18 (6), p.e0287768 |
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| 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. |
| doi_str_mv | 10.1371/journal.pone.0287768 |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0287768</identifier><identifier>PMID: 37384668</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Analysis ; Biology and Life Sciences ; Biomarkers ; Body mass index ; Cancer ; Cancer therapies ; Cholesterol ; Cholesterol, LDL ; Colorectal cancer ; Colorectal carcinoma ; Diabetes ; Diagnosis ; Disease ; Disease susceptibility ; Gene polymorphism ; Genetic analysis ; Genetic aspects ; Genetic diversity ; Genetic variance ; Health aspects ; High density lipoprotein ; Homeostasis ; Hypertension ; Lipids ; Low density lipoprotein ; Medical prognosis ; Medical screening ; Medicine and Health Sciences ; Metabolism ; Mortality ; Mucin ; Mucins ; Polymorphism ; Precision medicine ; Software ; Surgery ; Survival analysis ; Synergistic effect ; Tumors</subject><ispartof>PloS one, 2023-06, Vol.18 (6), p.e0287768</ispartof><rights>Copyright: © 2023 Kwon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Kwon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Kwon et al 2023 Kwon et al</rights><rights>2023 Kwon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c660t-db4747ad512616f9894cc1bac2938e6efacc04ba45359a07790975065b9581de3</citedby><cites>FETCH-LOGICAL-c660t-db4747ad512616f9894cc1bac2938e6efacc04ba45359a07790975065b9581de3</cites><orcidid>0000-0001-9475-6930</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310026/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310026/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37384668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kwon, Min Jung</creatorcontrib><creatorcontrib>Lee, Jeong Yong</creatorcontrib><creatorcontrib>Kim, Eo Jin</creatorcontrib><creatorcontrib>Ko, Eun Ju</creatorcontrib><creatorcontrib>Ryu, Chang Soo</creatorcontrib><creatorcontrib>Cho, Hye Jung</creatorcontrib><creatorcontrib>Jun, Hak Hoon</creatorcontrib><creatorcontrib>Kim, Jong Woo</creatorcontrib><creatorcontrib>Kim, Nam Keun</creatorcontrib><title>Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels</title><title>PloS one</title><addtitle>PLoS One</addtitle><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.</description><subject>Age</subject><subject>Analysis</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Body mass index</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cholesterol</subject><subject>Cholesterol, LDL</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Diabetes</subject><subject>Diagnosis</subject><subject>Disease</subject><subject>Disease susceptibility</subject><subject>Gene polymorphism</subject><subject>Genetic analysis</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic variance</subject><subject>Health aspects</subject><subject>High density 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Hoon</au><au>Kim, Jong Woo</au><au>Kim, Nam Keun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2023-06-29</date><risdate>2023</risdate><volume>18</volume><issue>6</issue><spage>e0287768</spage><pages>e0287768-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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 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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>37384668</pmid><doi>10.1371/journal.pone.0287768</doi><tpages>e0287768</tpages><orcidid>https://orcid.org/0000-0001-9475-6930</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Age Analysis Biology and Life Sciences Biomarkers Body mass index Cancer Cancer therapies Cholesterol Cholesterol, LDL Colorectal cancer Colorectal carcinoma Diabetes Diagnosis Disease Disease susceptibility Gene polymorphism Genetic analysis Genetic aspects Genetic diversity Genetic variance Health aspects High density lipoprotein Homeostasis Hypertension Lipids Low density lipoprotein Medical prognosis Medical screening Medicine and Health Sciences Metabolism Mortality Mucin Mucins Polymorphism Precision medicine Software Surgery Survival analysis Synergistic effect Tumors |
| title | Genetic variants of MUC4 are associated with susceptibility to and mortality of colorectal cancer and exhibit synergistic effects with LDL-C levels |
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