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.
Introduction:The CXC chemokines are unique cytokines that play a vital role in the progression of many cancers. Association between chemokine (C-X-C motif) receptor 2 (IL8RB) C1208T mutation and cancer risk remains incomprehensive.Methods:We therefore utilized odds ratios and in silico analysis to explore the relationship of IL8RB polymorphism on risk to cancer. Furthermore, we adopted gene set enrichment analysis to investigate the IL8RB expression in prostate adenocarcinoma.Results:A total of 14 case-control studies combined with 5299 cases and 6899 controls were included in our analysis. We revealed that individuals carrying TT genotype had an 14% increased cancer risk compared with those with TC + colon cancer (CC) genotype (odds ratio [OR] = 1.14, 95% CI = 1.05–1.25, P = .003, I2 = 35.6). Stratification analysis by race showed that East Asians with TT + TC genotype may have a 25% decreased cancer risk compared with control. Stratification analysis by cancer type revealed that individuals with TT genotype were associated with elevated risk of urinary cancer than control. The expression of IL8RB was attenuated in prostate adenocarcinoma.Conclusions:IL8RB C1208T may be correlated with the risk of cancer, especially prostate adenocarcinoma.
Background Currently, novel treatment methods for chemotherapy-naïve castration-resistant prostate cancer (CRPC) patients have been applied in clinical practice. Since the optimum regimen remains inconclusive, this study compares the efficacy and safety of these treatments by network meta-analysis. Methods The PubMed and ClinicalTrials.gov database and review articles before January 30, 2020 were searched and date were extracted. A total of 29908 patients with CRPC from 23 randomized controlled trials were included. Relative hazard ratios (HR) had been used to assess the effects on overall survival (OS), progression-free survival (PFS) or radiographic PFS (rPFS), and adverse events (AEs). We then pooled the data and used Bayesian and frequentist random-effects model to identify the best treatment strategy. Results Compared with the placebo, both Bayesian and frequentist random-effects network meta-analyses found that only enzalutamide and abiraterone had a significant effect in OS. Similar results were observed in PFS/rPFS. Bicalutamide, tasquinimod and orteronel could also improve rPFS. Enzalutamide only could improve rPFS more effectively than abiraterone with no significant differences in OS/PFS/AEs. In any subgroups of patients with age <75, ≥75 or ECOG score = 0,1 or Gleason score ≤7, ≥8, enzalutamide could improve the OS significantly. Nevertheless, the significant benefit of abiraterone was only found in patients with age <75 and ECOG score = 0. Conclusions Our network analysis suggested that both enzalutamide and abiraterone are optimal treatment for chemotherapy-naïve CRPC patients with age <75 and ECOG score = 0 for great improvement on OS and PFS. In addition, enzalutamide is also an optimum therapy for chemotherapy-naïve CRPC patients with age ≥75 and ECOG score = 1.
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