Associations of Genetic Polymorphisms of mTOR rs2295080 T/G and rs1883965 G/A with Susceptibility of Urinary System Cancers.

Zhichao Min,Yuanyuan Mi,Li Zuo,Hong Pan,Chao Lu,Lifeng Zhang,Hao Wu,Zhiwei Lv,Yujuan Zhang,Yangyang Sun,Ze Zhang,Bowen Tang,Silvia Angeletti

doi:10.1155/2022/1720851

Abstract

Background Genetic polymorphisms in mammalian target of rapamycin (mTOR) signaling axis can influence the susceptibility of cancer. The relationship between mTOR gene variants rs2295080 T/G and rs1883965 G/A and the risk of cancer remains inconsistent. The present study is aimed at comprehensively investigating the association between mTOR polymorphisms and susceptibility to cancer. Methods We conducted a comprehensive assessment using odds ratios (ORs), corresponding 95% confidence intervals (CIs), and in silico tools to evaluate the effect of mTOR variations. Immunohistochemical staining (IHS) and GSEA analysis were used to investigate the expression of mTOR in urinary system cancer. Results The pooled analysis involved 22 case-control studies including 14,747 cancer patients and 16,399 controls. The rs2295080 T/G polymorphism was associated with the risk of cancer (G-allele versus T-allele, OR = 0.89, 95%CI = 0.80–0.98, P = 0.023; GT versus TT, OR = 0.88, 95%CI = 0.81–0.96, P = 0.004; GG+GT versus TT, OR = 0.87, 95%CI = 0.78–0.96, P = 0.008), especially for cancers of the urinary system, breast, and blood. Variation rs1883965 G/A was associated with cancer susceptibility, especially for digestive cancer. IHS analysis showed that mTOR was upregulated in prostate and bladder cancer. GSEA revealed that the insulin signaling pathway, lysine degradation pathway, and mTOR signaling pathway were enriched in the high mTOR expression group. Conclusions The mTOR rs2295080 T/G polymorphism may be associated with susceptibility of urinary cancer. The expression of mTOR is positively correlated with tumor malignancy in prostate cancer.

Highlights

Malignant tumors are a major global public health problem [1]
gene set enrichment analysis (GSEA) revealed that the insulin signaling pathway (Figure 9(b)), lysine degradation pathway (Figure 9(c)), and mammalian target of rapamycin (mTOR) signaling pathway (Figure 9(d)) were enriched in the high mTOR expression group
The expression of mTOR was upregulated in bladder cancer (BLCA) and Prostate adenocarcinoma (PRAD) patients and was downregulated in kidney renal clear cell carcinoma (KIRC) samples

Summary

Introduction

Malignant tumors are a major global public health problem [1]. Over the past decades, cancer-related morbidity and mortality have increased. In Homo sapiens, missing phosphatase and tensin homologs of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signal transduction pathway on chromosome 10 are often activated in various carcinomas. They are involved in different cellular processes that include cell proliferation, angiogenesis, and Disease Markers. The present study is aimed at comprehensively investigating the association between mTOR polymorphisms and susceptibility to cancer. Immunohistochemical staining (IHS) and GSEA analysis were used to investigate the expression of mTOR in urinary system cancer. The mTOR rs2295080 T/G polymorphism may be associated with susceptibility of urinary cancer. The expression of mTOR is positively correlated with tumor malignancy in prostate cancer

Results

Discussion

Conclusion