Polymorphisms in the mTOR gene and risk of sporadic prostate cancer in an Eastern Chinese population.
Polymorphisms in the mTOR gene and risk of sporadic prostate cancer in an Eastern Chinese population.
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DOI：
10.1371/journal.pone.0071968
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wei Q
中科院分区：
文献类型：
--
作者：
Li Q;Gu C;Zhu Y;Wang M;Yang Y;Wang J;Jin L;Zhu ML;Shi TY;He J;Zhou X;Ye DW;Wei Q
mTOR 基因通过控制 mRNA 翻译、核糖体生物发生、自噬和代谢来调节细胞生长。 mTOR 表达异常增加与癌症发生相关，其功能性单核苷酸多态性 (SNP) 可能调节 mTOR 的表达，从而增加癌症风险。在一项针对 1004 例前列腺癌 (PCa) 病例和 1051 例无癌对照的医院病例对照研究中，我们对 mTOR 的 6 个潜在功能性 SNP（rs2536 T>C、rs1883965 G>A、rs1034528 G>C、rs17036508 T>C、rs3806317 A>G 和 rs2295080 T>G）并通过逻辑回归分析评估它们与 PCa 风险的关联。在单基因座分析中，我们发现与 mTOR rs2536 CT/CC 和 rs1034528 CG/CC 基因型相关的 PCa 风险显着增加 [调整后 OR = 1.42 (1.13–1.78)，P = 0.003 和 1.29 (1.07–1.55)， P = 0.007)，分别]，与常见的纯合基因型相比， 而与野生型 TT 基因型相比，mTOR rs2295080 GT/GG 基因型与 PCa 风险降低相关[调整后 OR = 0.76 (0.64–0.92)，P = 0.003]。在对六个 SNP 的综合分析中，我们发现，与携带少于两种不良基因型的个体相比，携带两种或两种以上不良基因型的个体患 PCa 的风险增加 [调整后 OR = 1.24 (1.04–1.47)，P = 0.016]。在多维降维分析中，体重指数（BMI）是所有七个因素中CVC最高（100%）和预测误差最低（42.7%）的最佳单因素模型。包含 BMI、rs17036508 和 rs2536 之间交互作用的模型是最佳三因素模型，其 CVC 最高（100%），预测误差最低，为 41.9%。这些发现表明，mTOR SNP 可能会增加中国东部男性患 PCa 的风险，但效果较弱，需要通过更大规模的人群研究进一步验证。
The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Abnormally increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and thus contribute to cancer risk. In a hospital-based case-control study of 1004 prostate cancer (PCa) cases and 1051 cancer-free controls, we genotyped six potentially functional SNPs of mTOR (rs2536 T>C, rs1883965 G>A, rs1034528 G>C, rs17036508 T>C, rs3806317 A>G, and rs2295080 T>G) and assessed their associations with risk of PCa by using logistic regression analysis. In the single-locus analysis, we found a significantly increased risk of PCa associated with mTOR rs2536 CT/CC and rs1034528 CG/CC genotypes [adjusted OR = 1.42 (1.13–1.78), P = 0.003 and 1.29 (1.07–1.55), P = 0.007), respectively], compared with their common homozygous genotypes, whereas mTOR rs2295080 GT/GG genotypes were associated with a decreased risk of PCa [adjusted OR = 0.76 (0.64–0.92), P = 0.003], compared with wild-type TT genotypes. In the combined analysis of the six SNPs, we found that individuals carrying two or more adverse genotypes had an increased risk of PCa [adjusted OR = 1.24 (1.04–1.47), P = 0.016], compared with individuals carrying less than two adverse genotypes. In the multiple dimension reduction analysis, body mass index (BMI) was the best one-factor model with the highest CVC (100%) and the lowest prediction error (42.7%) among all seven factors. The model including an interaction among BMI, rs17036508, and rs2536 was the best three-factor model with the highest CVC (100%) and the lowest prediction error of 41.9%. These findings suggested that mTOR SNPs may contribute to the risk of PCa in Eastern Chinese men, but the effect was weak and needs further validation by larger population-based studies.
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