3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis
Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastas...
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2021-06-01
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author | Young-Joo Jeon Sung-Hwan Cho Eo-Jin Kim Chang-Soo Ryu Han-Sung Park Jong-Woo Kim Jeong-Yong Lee Hui-Jeong An Nam-Keun Kim |
author_facet | Young-Joo Jeon Sung-Hwan Cho Eo-Jin Kim Chang-Soo Ryu Han-Sung Park Jong-Woo Kim Jeong-Yong Lee Hui-Jeong An Nam-Keun Kim |
author_sort | Young-Joo Jeon |
collection | DOAJ |
description | Colorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastasis for many cancers, including CRC. Moreover, recent studies have reported that polymorphisms in specific microRNA (miRNA)-binding regions, which are located in the 3′-untranslated region (UTR) of miRNA-regulated genes, are present in a variety of cancers. Here, we investigated the association between two thymidylate synthase (<i>TYMS</i> or <i>TS)</i> 3′-UTR polymorphisms, 1100T>C [rs699517] and 1170A>G [rs2790], and CRC susceptibility and progression in Korean patients. A total of 450 CRC patients and 400 healthy controls were enrolled in this study, and genotyping at the TS locus was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) or TaqMan allelic discrimination assays. We found that TS 1170A>G genotypes, as well as the TS 1100T-1170G and 1100C-1170A haplotypes, are strongly associated with CRC. The TS 1100TC+CC type was associated with a poor survival (OS and RFS) rate. In addition, levels of the TS 1100C and TS 1170G allele were found to be significantly increased in CRC tissue. Our study provides the first evidence for 3′-UTR variants in TS genes as potential biomarkers of CRC prognosis and prevention. |
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spelling | doaj.art-fd0e769716e54f1694eea8f7a44051172023-11-21T23:29:23ZengMDPI AGJournal of Personalized Medicine2075-44262021-06-0111653710.3390/jpm110605373′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and PrognosisYoung-Joo Jeon0Sung-Hwan Cho1Eo-Jin Kim2Chang-Soo Ryu3Han-Sung Park4Jong-Woo Kim5Jeong-Yong Lee6Hui-Jeong An7Nam-Keun Kim8Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaDivision of Hematology/Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 06351, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaCHA Bundang Medical Center, Department of Surgery, CHA University, Seongnam 13496, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaDepartment of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, KoreaColorectal cancer (CRC) is the third most common type of cancer and the second leading cause of cancer-related mortality in Western countries. Polymorphisms in one-carbon metabolism and angiogenesis-related genes have been shown to play important roles in tumor development, progression, and metastasis for many cancers, including CRC. Moreover, recent studies have reported that polymorphisms in specific microRNA (miRNA)-binding regions, which are located in the 3′-untranslated region (UTR) of miRNA-regulated genes, are present in a variety of cancers. Here, we investigated the association between two thymidylate synthase (<i>TYMS</i> or <i>TS)</i> 3′-UTR polymorphisms, 1100T>C [rs699517] and 1170A>G [rs2790], and CRC susceptibility and progression in Korean patients. A total of 450 CRC patients and 400 healthy controls were enrolled in this study, and genotyping at the TS locus was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) or TaqMan allelic discrimination assays. We found that TS 1170A>G genotypes, as well as the TS 1100T-1170G and 1100C-1170A haplotypes, are strongly associated with CRC. The TS 1100TC+CC type was associated with a poor survival (OS and RFS) rate. In addition, levels of the TS 1100C and TS 1170G allele were found to be significantly increased in CRC tissue. Our study provides the first evidence for 3′-UTR variants in TS genes as potential biomarkers of CRC prognosis and prevention.https://www.mdpi.com/2075-4426/11/6/537thymidylate synthase3′-UTRmiRNA polymorphismcolorectal cancerprevalenceprognosis |
spellingShingle | Young-Joo Jeon Sung-Hwan Cho Eo-Jin Kim Chang-Soo Ryu Han-Sung Park Jong-Woo Kim Jeong-Yong Lee Hui-Jeong An Nam-Keun Kim 3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis Journal of Personalized Medicine thymidylate synthase 3′-UTR miRNA polymorphism colorectal cancer prevalence prognosis |
title | 3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis |
title_full | 3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis |
title_fullStr | 3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis |
title_full_unstemmed | 3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis |
title_short | 3′-UTR Polymorphisms in Thymidylate Synthase with Colorectal Cancer Prevalence and Prognosis |
title_sort | 3 utr polymorphisms in thymidylate synthase with colorectal cancer prevalence and prognosis |
topic | thymidylate synthase 3′-UTR miRNA polymorphism colorectal cancer prevalence prognosis |
url | https://www.mdpi.com/2075-4426/11/6/537 |
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