Lu Xiaoling, Liu Meitong, Liao Yuxiao, Huang Chao, Chai Longlong, Jin Yuchen, Xiong Qiantao, Chen Bifeng
Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China.
Department of Biological Science and Technology, School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China; Department of Laboratory, Maternal and Child Health Hospital of Hubei Province, Wuhan, China.
Pathol Res Pract. 2022 Jan;229:153696. doi: 10.1016/j.prp.2021.153696. Epub 2021 Nov 23.
mTOR, mLST8 and RAPTOR are the core components of mTORC1, which has been found to be closely related to tumorigenesis. Currently, multiple single nucleotide polymorphisms (SNPs) in mTOR gene (rs2295080, rs17036508 and rs1034528), mLST8 gene (rs3160 and rs26865) and RPTOR gene (rs1062935, rs3751932, rs3751834, rs12602885) have been extensively studied for their associations with cancer risk. However, the results remained inconclusive and conflicting. Therefore, we here performed a meta-analysis of all available studies to investigate the association between these SNPs and cancer risk.
Up to April 2021, 25 related publications were retrieved and included in this meta-analysis. The odds ratios (ORs) and 95% confidence intervals (CIs) calculated by fixed or random effects models were applied to assess the strength of association. Trial Sequential Analysis (TSA) was conducted to weaken the random error and enhance the reliability of evidence.
After Bonferroni correction, it was revealed that rs3160, rs26865, rs1062935, rs3751932, rs3751834 and rs10602885 were not associated with cancer risk. However, rs17036508 and rs1034528 showed significant association with total cancer risk. A significant association was also found between rs2295080 and total cancer risk, and stratified analysis by cancer type suggested that rs2295080 was specifically associated with acute lymphoblastic leukemia risk, prostate cancer risk, and breast cancer risk.
The present meta-analysis suggested that the rs2295080, rs17036508 and rs1034528 polymorphisms in mTOR gene may be the susceptive factors for cancer development, while the target genetic polymorphisms in mLST8 gene or RPTOR gene may not be associated with cancer risk. However, these findings remain to be confirmed or further reinforced in large and well-designed studies in different ethnic populations.
mTOR、mLST8和RAPTOR是mTORC1的核心组成部分，已发现其与肿瘤发生密切相关。目前，mTOR基因（rs2295080、rs17036508和rs1034528）、mLST8基因（rs3160和rs26865）和RPTOR基因（rs1062935、rs3751932、rs3751834、rs12602885）中的多个单核苷酸多态性（SNP）与癌症风险的关联已得到广泛研究。然而，结果仍无定论且相互矛盾。因此，我们在此对所有可用研究进行荟萃分析，以探讨这些SNP与癌症风险之间的关联。
截至2021年4月，检索到25篇相关出版物并纳入本荟萃分析。采用固定或随机效应模型计算的比值比（OR）和95%置信区间（CI）来评估关联强度。进行了序贯试验分析（TSA）以减少随机误差并提高证据的可靠性。
经过Bonferroni校正后，发现rs3160、rs26865、rs1062935、rs3751932、rs3751834和rs10602885与癌症风险无关。然而，rs17036508和rs1034528与总体癌症风险显示出显著关联。rs2295080与总体癌症风险之间也发现了显著关联，按癌症类型进行的分层分析表明，rs2295080与急性淋巴细胞白血病风险、前列腺癌风险和乳腺癌风险特别相关。
本荟萃分析表明，mTOR基因中的rs2295080、rs17036508和rs1034528多态性可能是癌症发生的易感因素，而mLST8基因或RPTOR基因中的目标基因多态性可能与癌症风险无关。然而，这些发现仍有待在不同种族人群中进行的大型且设计良好的研究中得到证实或进一步加强。
