Abstract
BackgroundThe 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 FindingsIn 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/SignificancesIn 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.
Highlights
Prostate cancer (PCa) is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males according to the latest report released by the International Agency for Research on Cancer (IARC) in 2008 [1]
Ethnic specific single institutional case-control study, we investigated the associations between six potentially functional single nucleotide polymorphisms (SNPs) of the mTOR gene and PCa risk, and we found that the rs2536 C, rs1034528 C, and rs2295080 G variant genotypes were associated with PCa risk, and the effects were more evident in subgroups of age#69, body mass index (BMI)#24 kg/m2, and eversmokers
To the best of our knowledge, this is the first post-genome-wide association studies (GWASs) study that focused on the associations of these six potentially functional mTOR SNPs with PCa risk
Summary
Prostate cancer (PCa) is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males according to the latest report released by the International Agency for Research on Cancer (IARC) in 2008 [1]. Accumulated evidence from genome-wide association studies (GWASs) suggests that more than 40 single nucleotide polymorphisms (SNPs) are associated with human PCa risk, some of which were confirmed in Chinese male populations. As a key downstream effector of PI3K/AKT/mTOR pathway, the mTOR has been confirmed to be a central regulator of vital cellular processes, such as cell growth, proliferation, metabolism, migration, and apoptosis, based on the in vivo and in vitro investigations [9,10,11,12]. The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism. Increased expression of mTOR was associated with carcinogenesis, and its functional single nucleotide polymorphisms (SNPs) may regulate the expression of mTOR and contribute to cancer risk
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