Gene polymorphisms in the PI3K/AKT/mTOR signaling pathway contribute to prostate cancer susceptibility in Chinese men
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Ting Liu1,*, Abulajiang Gulinaer1,*, Xiaoli Shi1, Feng Wang2, Hengqing An2, Wenli Cui1 and Qiaoxin Li1
1Department of Pathology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, China
2Department of Urology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, China
*These authors have contributed equally to this work and should be considered co-first authors
Qiaoxin Li, email: [email protected]
Keywords: case-control study, prostate cancer, genetic susceptibility, PI3K/AKT/mTOR pathway, polymorphism
Abbreviations: SNPs: single nucleotide polymorphisms; PCa: prostate cancer; OR: odds ratio; CI: confidence interval
Received: February 24, 2017 Accepted: April 15, 2017 Published: May 22, 2017
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.
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