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...

Full description

Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Journal of Personalized Medicine
Subjects:
Online Access:https://www.mdpi.com/2075-4426/11/6/537
_version_ 1797530772162215936
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.
first_indexed 2024-03-10T10:33:46Z
format Article
id doaj.art-fd0e769716e54f1694eea8f7a4405117
institution Directory Open Access Journal
issn 2075-4426
language English
last_indexed 2024-03-10T10:33:46Z
publishDate 2021-06-01
publisher MDPI AG
record_format Article
series Journal of Personalized Medicine
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
work_keys_str_mv AT youngjoojeon 3utrpolymorphismsinthymidylatesynthasewithcolorectalcancerprevalenceandprognosis
AT sunghwancho 3utrpolymorphismsinthymidylatesynthasewithcolorectalcancerprevalenceandprognosis
AT eojinkim 3utrpolymorphismsinthymidylatesynthasewithcolorectalcancerprevalenceandprognosis
AT changsooryu 3utrpolymorphismsinthymidylatesynthasewithcolorectalcancerprevalenceandprognosis
AT hansungpark 3utrpolymorphismsinthymidylatesynthasewithcolorectalcancerprevalenceandprognosis
AT jongwookim 3utrpolymorphismsinthymidylatesynthasewithcolorectalcancerprevalenceandprognosis
AT jeongyonglee 3utrpolymorphismsinthymidylatesynthasewithcolorectalcancerprevalenceandprognosis
AT huijeongan 3utrpolymorphismsinthymidylatesynthasewithcolorectalcancerprevalenceandprognosis
AT namkeunkim 3utrpolymorphismsinthymidylatesynthasewithcolorectalcancerprevalenceandprognosis