TYMS plays an important roles in folate metabolism and DNA repair. Previous clinical studies have shown that TYMS polymorphisms are associated with various of cancers, such as gastric cancer, lung cancer, hepatocellular carcinoma, and acute lymphoblastic leukemia. Additionally, TYMS polymorphisms may predict the chemosensitivity to 5-fluorouracil, doxorubicin, cyclophosphamide, pemetrexed and so on.[20, 21, 9] TYMS SNPs influence cancer susceptibility and chemosensitivity via effects on TYMS expression and its effects differ with respect to race.[23, 11] However, inconsistent results have been obtained regarding the association between the miRNA binding sites of TYMS SNPs and breast cancer and data from Asian populations are lacking.
Guan et al. found that rs2790 and rs1059394 have no effect in non-Hispanic white women. We found that rs2790 may increase the breast cancer risk and the C allele of rs1059394 is closely related to a more advanced clinical stage among Chinese Han people. Rs2790 is in linkage disequilibrium with a functional SNP (TSER, three or two repeats of a 28-bp sequence) in TYMS and modulates TYMS expression by its effects on the binding of hsa-miR-1248 to its target gene. However, little is known about the functionality of these two SNPs. More experimental studies are urgently needed to clarify the mechanism underlying the effects of TYMS polymorphisms.
Moreover, we used data from the GEO database to evaluate the difference of TYMS expression between tumor and para-carcinoma tissues among Chinese patients. And we found that tumor tissues had higher TYMS expression. The effect of TYMS expression level on the prognosis among Chinese breast cancer patients was showed that patients with higher expression levels of TYMS had a worse OS. D'Arcy et al. reported that African American women with breast cancer have higher expression levels of TYMS and a poorer prognosis than those of Caucasian women, which means there are racial differences in the TYMS expression. China is a multi-ethnic country, so it will be valuable to compare the difference between different nationalities.
We conducted a hospital-based study and all samples were obtained from the northwest region of China; therefore, the selection bias is unavoidable. Large-scale multicenter studies are needed to verify our results. TYMS expression and the prognosis analyses were conducted based on GEO database; we will further detect TYMS expression levels among different types of breast cancer and all patients will be follow up to obtain survival statistics. Furthermore, the influence of ethnic difference on TYMS expression will be a major focus of future research.
In conclusion, carriers of the GG genotype of rs2790 may have a higher risk of breast cancer and the C allele of rs1059394 may signify a poorer TNM stage. In addition, the tumor tissues had higher TYMS than para-carcinoma tissues in breast cancer and patients with higher TYMS levels may be related to a worse OS.