Abstract
BackgroudGenetic variations in a PTEN/AKT/mTOR signaling axis may influence cellular functions including cell growth, proliferation and apoptosis, and then increase the individual’s risk of cancer. Accordingly, we explore the association between single nucleotide polymorphisms (SNPs) of these genes and prostate cancer (PCa) in our Chinese population.MethodsSubjects were recruited from 666 PCa patients and 708 cancer-free controls, and eight SNPs in the PTEN/AKT/mTOR axis were determined by the TaqMan assay. Odds ratios (OR) and 95% confidence intervals (95% CI) were evaluated by logistic regression.ResultsWe observed significant associations between PCa risk and mTOR rs2295080 [P = 0.027, OR = 0.85, 95%CI = 0.74–0.98], and AKT2 rs7254617 (P = 0.003, OR = 1.35, 95%CI = 1.11–1.64). When estimated these two SNPs together, the combined genotypes with 2–4 risk alleles (rs2295080 T and rs7254617 A alleles) were associated with an increased risk of PCa compared with 0–1 risk alleles, which was more pronounced among subgroups of age >71 years, smokers, drinkers and no family history of cancer. Results of stratified analyses by cliniopathological parameters revealed that the frequencies of the combined genotypes with 2–4 risk alleles in advanced stage were significantly higher than in localized stage(P = 0.022), but there was no significant association in Gleason score and PSA level.ConclusionOur results indicate, for the first time that the two variants in AKT2 and mTOR, particularly the joint genotypes with 2–4 risk alleles may influence PCa susceptibility and progression in Chinese, and the association appeared to be more strong in the subgroup of smokers and drinkers.
Highlights
Prostate cancer(PCa) accounts for one-fourth of all tumors diagnosed in men in the United States, with an estimated 217,730 new cases and 32,050 deaths in 2010 [1]
A significantly higher proportion of the cases were of smoking, drinking and positive for family history compared with controls (P = 0.013, P = 0.023, P,0.001, respectively)
We dichotomized the combined risk alleles into two groups by the number of risk alleles and used the combined genotypes with 0–1 risk alleles as the reference, we found that genotypes with 2–4 risk alleles were in accordance with a statistically significantly increased susceptibility to prostate cancer (PCa)(OR = 1.41, 95%confidence intervals (CIs) = 1.12–1.79, P = 0.004)
Summary
Prostate cancer(PCa) accounts for one-fourth of all tumors diagnosed in men in the United States, with an estimated 217,730 new cases and 32,050 deaths in 2010 [1]. The occurrence of PCa has steadily increased in recent years in China [2]. Major risk factors for PCa are age, ethnic origin, lifestyle, environmental factors and genetic variants [3]. Many people are exposed to these risk factors, only a small portion of the exposed individuals develop PCa, indicating that genetic variation partly contribute to the development and progression of PCa [4]. It is of great clinical significance to identify more molecular markers for detection and diagnosis of PCa. it is of great clinical significance to identify more molecular markers for detection and diagnosis of PCa Among these molecular markers, the associations between gene polymorphisms and predisposition to PCa have been extensively investigated in recent years [5,6,7]
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