mTOR 基因多态性与华东地区散发性前列腺癌风险的关系。
Polymorphisms in the mTOR gene and risk of sporadic prostate cancer in an Eastern Chinese population.
机构信息
Cancer Institute, Fudan University Shanghai Cancer Institute, Shanghai, China.
出版信息
PLoS One. 2013 Aug 5;8(8):e71968. doi: 10.1371/journal.pone.0071968. Print 2013.
BACKGROUND
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.
METHODOLOGY/PRINCIPAL FINDINGS: 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.
CONCLUSIONS/SIGNIFICANCES: 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.
背景
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 的异常高表达与致癌作用有关，其功能单核苷酸多态性（SNP）可能调节 mTOR 的表达，从而影响癌症风险。
方法/主要发现：在一项基于医院的 1004 例前列腺癌（PCa）病例和 1051 例无癌症对照的病例对照研究中，我们对 mTOR（rs2536 T>C、rs1883965 G>A、rs1034528 G>C、rs17036508 T>C、rs3806317 A>G 和 rs2295080 T>G）的六个潜在功能 SNP 进行了基因分型，并使用逻辑回归分析评估了它们与 PCa 风险的关联。
结论/意义：在单基因座分析中，我们发现 mTOR rs2536 CT/CC 和 rs1034528 CG/CC 基因型与 PCa 风险显著增加相关[校正 OR=1.42（1.13-1.78），P=0.003 和 1.29（1.07-1.55），P=0.007]，与常见的纯合基因型相比，而 mTOR rs2295080 GT/GG 基因型与 PCa 风险降低相关[校正 OR=0.76（0.64-0.92），P=0.003]，与野生型 TT 基因型相比。在对六个 SNP 的综合分析中，我们发现携带两个或更多不利基因型的个体患 PCa 的风险增加[校正 OR=1.24（1.04-1.47），P=0.016]，与携带不到两个不利基因型的个体相比。在多维降维分析中，体重指数（BMI）是所有七个因素中最佳的单因素模型，具有最高的 CVC（100%）和最低的预测误差（42.7%）。包括 BMI、rs17036508 和 rs2536 之间相互作用的模型是最佳的三因素模型，具有最高的 CVC（100%）和最低的预测误差 41.9%。这些发现表明 mTOR SNP 可能导致东亚男性患 PCa 的风险增加，但作用较弱，需要更大的基于人群的研究进一步验证。
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