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J Cancer 2018; 9(8):1448-1454. doi:10.7150/jca.23566 This issue Cite

Research Paper

Genetic Variants Within MTORC1 Genes Predict Gastric Cancer Prognosis in Chinese Populations

Wenji Xue^{1,2 *}, Mengyun Wang^3*, Li Zhang¹, Jianchun Gu¹, Xueru Zhu¹, Yiwei Wang¹, Ruifen Wang⁴, Lifeng Wang⁴, Weiye Wang⁵, Xue-Feng Wang^6,7, Jia-Wei Mei^6,7, Leizhen Zheng^1✉, Mei-Ling Zhu^1✉

1. Department of Oncology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China
2. Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China
3. Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
4. Department of Pathology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China
5. MOE-Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
6. Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China
7. Institute of Biliary Tract Disease, Xinhua Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, 200092, China
^* These authors contributed equally to this paper.

✉ Corresponding authors: Mei-Ling Zhu, Department of Oncology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. Email: zhumeilingcom.cn; Leizhen Zheng, Department of Oncology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China. Email: zhengleizhencom.cn. More

Abstract

Objective: Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions in gastric cancer (GC). Previous studies demonstrated genetic variants within mTORC1 genes were associated with GC risk. However, no studies reported the associations between genetic variants within mTORC1 genes and GC prognosis. Herein, we firstly assessed the associations of genetic variants of mTORC1 genes with overall survival (OS) of GC in Chinese populations.

Methods: We genotyped eight single nucleotide polymorphisms (SNPs) in mTORC1 genes (i.e., rs2536 T>C and rs1883965 G>A for mTOR, rs3160 T>C and rs26865 A>G for MLST8, rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A for RPTOR) by the TaqMan method in 197 Chinese GC patients who had surgical resection in Xinhua Hospital. We conducted Kaplan-Meier survival plots and Cox hazards regression analysis to explore the associations of these SNPs with OS.

Results: The single-locus analysis indicated that RPTOR rs1062935 T>C was associated with an increased risk of poor GC prognosis (CC vs. TT/TC: adjusted Hazard ratio (HR) = 1.71, 95% confidence interval (CI) = 1.04-2.82). The combined analysis of all eight SNPs showed that patients with more than three risk genotypes significantly increased risk of death (adjusted HR = 2.44, 95% CI = 1.30-4.58), when compared to those with three or less risk genotypes.

Conclusions: Our findings indicated that genetic variants within mTORC1 genes may predict GC prognosis in Chinese populations. The results need to be validated in future studies with larger sample sizes.

Keywords: mTORC1, genetic variants, gastric cancer, clinical outcome

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