Association Between Genetic Polymorphisms In TYMS And Glioma Risk In Chinese Patients: A Case-Control Study

Li Yao; Linghui Zhou; Yujiao Deng; Yi Zheng; Pengtao Yang; Meng Wang; Shanshan Dong; Qian Hao; Peng Xu; Na Li; Ying Wu; Zhen Zhai; Lijuan Lyu; Zhijun Dai

doi:10.2147/OTT.S221204

Association Between Genetic Polymorphisms In TYMS And Glioma Risk In Chinese Patients: A Case-Control Study

Onco Targets Ther. 2019 Oct 7:12:8241-8247. doi: 10.2147/OTT.S221204. eCollection 2019.

Authors

Li Yao^#¹, Linghui Zhou^#^{2

3}, Yujiao Deng^#^{2

3}, Yi Zheng^{2

3}, Pengtao Yang², Meng Wang², Shanshan Dong⁴, Qian Hao^{2

3}, Peng Xu^{2

3}, Na Li^{2

3}, Ying Wu^{2

3}, Zhen Zhai^{2

3}, Lijuan Lyu^{2

3}, Zhijun Dai^{2

3}

Affiliations

¹ Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, People's Republic of China.
² Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, People's Republic of China.
³ Department of Breast Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, People's Republic of China.
⁴ School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, People's Republic of China.

^# Contributed equally.

Abstract

Background: Thymidylate synthase (TYMS) polymorphisms are reported to be related to susceptibility to some cancers. However, no study exists on TYMS polymorphisms and glioma risk. This study aimed to evaluate the relationship between two common TYMS gene variants (rs1059394 C>T, rs2847153 G>A) and glioma susceptibility.

Methods: This case-control study included 605 patients and 1300 cancer-free individuals. Genotyping was performed using Sequenom Mass-ARRAY. We determined odds ratios (ORs) and their 95% confidence intervals (CIs) to estimate the correlations.

Results: The analysis revealed that rs1059394 TT and CT+TT genotype had significantly low glioma risk (TT to CC: OR = 0.71, 95% CI = 0.52-0.97, P = 0.03; CT+TT to CC: OR = 0.74, 95% CI = 0.55-0.99, P = 0.04). However, no significant difference was found between rs2847153 and glioma risk in any genetic model (P﹥0.05). In high-grade gliomas, the GA and GA+AA genotypes of rs2847153 made the majority of genotypes, compared with GG genotype (GA to GG: OR = 2.01, 95% CI = 1.39-2.91, P < 0.001; GA+AA to GG: OR = 1.78, 95% CI =1.25-2.54, P < 0.001). Moreover, online expression quantitative trait locus (eQTL) analysis indicated that these two polymorphisms may alter TYMS gene expression in transformed fibroblast cells.

Conclusion: Our study provides evidence of the effect of TYMS rs1059394 on the susceptibility of glioma. In high-grade gliomas, compared with GG genotype, the GA and GA+AA genotypes of rs2847153 comprise a larger proportion.

Keywords: TYMS; case-control study; gene variant; glioma; susceptibility.

Grants and funding

National Natural Science Foundation of China; Grant/Award Number: 81471670. Key Research and Development Plan, Shaanxi Province, China; Grant/Award Number: 2017ZDXM-SF-066.