Abstract
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 (TYMS or TS) 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.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide, with 1,849,518 new cases diagnosed per year and representing 10.2% of all new cancer cases
These single nucleotide polymorphisms (SNPs) are found at minor allele frequencies of >5% in the Asian population; it is not known whether they display any genetic associations with CRC or if there is variation in thymidylate synthase (TS) expression as a function of these 30 -untranslated region (UTR) polymorphisms
We found that CRC patients were significantly more likely to have HTN (p < 0.001), diabetes mellitus (DM) (p < 0.001), low high-density lipoprotein cholesterol (HDL-C) levels (p < 0.001), and decreased fatty acids (FA) levels (p = 0.043), relative to healthy controls
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide, with 1,849,518 new cases diagnosed per year and representing 10.2% of all new cancer cases. One previous study showed that CRC tumor tissue containing the triple repeat (3R) in the TS enhancer exhibits 4-fold higher TS mRNA levels than CRC tumor tissue from patients who carry the 2R variant (p < 0.004) [22] This polymorphism is of clinical significance, as greater TS enzyme activity is observed in cancer cells containing the triple repeat than for those with the double repeat [19,23]. We performed a database search and identified two single nucleotide polymorphisms (SNPs) in the TS 30 -UTR: TS 1100T>C (rs699517) and TS 1170A>G (rs2790) These SNPs are found at minor allele frequencies of >5% in the Asian population; it is not known whether they display any genetic associations with CRC or if there is variation in TS expression as a function of these 30 -UTR polymorphisms. In this study, we investigated whether these polymorphisms in the TS 30 -UTR correlate with CRC development and TS mRNA expression levels
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
