Gene polymorphisms in the PI3K/AKT/mTOR signaling pathway contribute to prostate cancer susceptibility in Chinese men

Ting Liu,Abulajiang Gulinaer,Wenli Cui,Xiaoli Shi,Feng Wang,Qiaoxin Li,Hengqing An

doi:10.18632/oncotarget.18064

Ting Liu, Abulajiang Gulinaer + Show 5 more

Open Access

https://doi.org/10.18632/oncotarget.18064

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Abstract

In this hospital-based case-control study of 413 prostate cancer (PCa) cases and 807 cancer-free controls, we investigated the role of functional single nucleotide polymorphisms (SNPs) of pivotal genes in the PI3K/AKT/mTOR pathway. We genotyped 17 SNPs in mTOR, Raptor, AKT1, AKT2, PTEN, and K-ras and found that 4 were associated with PCa susceptibility. Among the variants, the homozygote variant CC genotype of mTOR rs17036508 C>T were associated with higher PCa risk than the wild TT genotypes (adjusted OR = 3.73 (95% CI = 1.75-7.94), P = 0.001). The GT genotype of mTOR rs2295080 G>T was more protective than the TT genotypes (adjusted OR=0.54 (95% CI=0.32-0.91), P=0.020). The distributions of Raptor rs1468033 A>G genotypes differed between cases and controls, especially in subgroups defined by age, BMI, smoking status, and ethnicity. The CT/CC genotypes of AKT2 rs7250897 C>T were associated with an increased risk of PCa, particularly in subgroups of age >71 and BMI >24 kg/m2. These findings suggest that SNPs in the PI3K/AKT/mTOR pathway may contribute to the risk of PCa in Chinese men.

Highlights

Prostate cancer (PCa) is the leading malignancy in developed nations and ranks second in cancer deaths worldwide [1, 2]
In this hospital-based case-control study of 413 prostate cancer (PCa) cases and 807 cancer-free controls, we investigated the role of functional single nucleotide polymorphisms (SNPs) of pivotal genes in the PI3K/AKT/mTOR pathway
Among the 17 SNPs analyzed, three variants of two genes were associated with PCa risk, and another variant was associated with PCa risk by stratification analysis (Table 2)

Summary

Introduction

Prostate cancer (PCa) is the leading malignancy in developed nations and ranks second in cancer deaths worldwide [1, 2]. Environmental and genetic factors are associated with PCa carcinogenesis, the actual causes are unknown. Published genome-wide association studies (GWAS) identified 40 single nucleotide polymorphisms (SNPs) that were associated with human PCa risk [6]. Lu et al demonstrated that SNPs associated with PCa risk were enriched in the androgen receptor (AR)-binding sites [7, 8]. These findings led to further functional studies to better understand PCa susceptibility

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