Abstract
There is still no conclusion on the potential effect of the rs2295080 and rs2536 polymorphisms of mTOR (mammalian target of rapamycin) gene on different cancers. Herein, we performed a comprehensive assessment using pooled analysis, FPRP (false-positive report probability), TSA (trial sequential analysis), and eQTL (expression quantitative trait loci) analysis. Eighteen high-quality articles from China were enrolled. The pooled analysis of rs2295080 with 9502 cases and 10,965 controls showed a decreased risk of urinary system tumors and specific prostate cancers [TG vs. TT, TG+GG vs. TT and G vs. T; P<0.05, OR (odds ratio) <1]. FPRP and TSA data further confirmed these results. There was an increased risk of leukemia [G vs. T, GG vs. TT, and GG vs. TT+TG genotypes; P<0.05, OR>1]. The eQTL data showed a potential correlation between the rs2295080 and mTOR expression in whole blood samples. Nevertheless, FPRP and TSA data suggested that more evidence is required to confirm the potential role of rs2295080 in leukemia risk. The pooled analysis of rs2536 (6653 cases and 7025 controls) showed a significant association in the subgroup of “population-based” control source via the allele, heterozygote, dominant, and carrier comparisons (P<0.05, OR>1). In conclusion, the TG genotype of mTOR rs2295080 may be linked to reduced susceptibility to urinary system tumors or specific prostate cancers in Chinese patients. The currently data do not strongly support a role of rs2295080 in leukemia susceptibility. Large sample sizes are needed to confirm the potential role of rs2536 in more types of cancer.
Highlights
Received: 03 June 2019Revised: 03 June 2020Accepted: 08 June 2020Accepted Manuscript online: Version of Record published: Considering the involvement of genetic and environmental factors in tumorigenesis [1,2], it is very informative to discover cancer-associated SNPs [3]
11,204 subjects reported that the rs699947 polymorphism within the VEGF gene was associated with an increased risk of bladder cancer and renal cell carcinoma in Asians
= 0.027, odds ratio (OR) = 0.88 (0.79–0.99)] comparisons (Table 2). These results indicated that the TG genotype of mTOR rs2295080 is likely to be associated with a decreased susceptibility to urinary system tumors and specific prostate cancers in Chinese patients
Summary
Considering the involvement of genetic and environmental factors in tumorigenesis [1,2], it is very informative to discover cancer-associated SNPs (single-nucleotide polymorphisms) [3]. Three factors, including cancer type, genotyping method and control source, were considered for the subgroup analyses. Selection factors included overlapping or duplicated data; reviews, case reports, and trials; cellular or animal assays; conference abstracts; meta-analyses; and other diseases, genes or SNPs. The genotype frequency distribution in controls was required to follow HardyñWeinberg equilibrium (HWE). The genotype frequency data of the mTOR gene rs2295080 and rs2536 polymorphisms in both cancer cases and negative controls needed to be extractable from the studies. We extracted the information independently and utilized a table to summarize the following features: first author name, year of publication, genotypic/allelic frequency, cancer type, source of control, genotyping method, and sample size. An overall meta-analysis and subsequent subgroup analyses according to three factors (control source, genotyping method, and cancer type) were conducted. TSA viewer software (Copenhagen Trial Unit, Copenhagen) was employed to generate a TSA plot with the required information size (RIS) line and TSA monitoring boundaries with a type I error limit of 5% and a statistical power of 80%
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