Polymorphisms in the mTOR Gene and Risk of Sporadic Prostate Cancer in an Eastern Chinese Population

Li, Qiao‐Xin; Gu, Chengyuan; Zhu, Yao; Wang, Mengyun; Yang, Yajun; Wang, Jiucun; Jin, Li; Zhu, Mei Ling; Shi, Ting; He, Jing; Zhou, Xiaoyan; Ye, Ding Wei; Wei, Qingyi

doi:10.1371/journal.pone.0071968

Cited by 29 publications

(53 citation statements)

References 38 publications

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“…Single SNP are well known to have relatively weak predictive power in cellular signaling pathways, while this is greatly enhanced when multiple SNPS are combined (Li et al 2013a). When we combined two risk SNPs of mLST8:rs26865 and mLST8:rs3160, the cumulative effect of the risk genotype was "dose dependent," that is, as the number of observed risk genotypes increased, the risk of brain metastases also increased significantly.…”

Section: Discussionmentioning

confidence: 99%

Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

Huang

Weng

et al. 2019

J Cancer Res Clin Oncol

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Purpose The mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a vital role in cancer development and progression. This study aimed to investigate the relationship between genotype variants in mTORC1 pathway and the risk of brain metastasis (BM) in patients with non-small cell lung cancer (NSCLC). Methods We extracted genomic DNA from blood samples of 501 NSCLC patients and genotyped eight single-nucleotide polymorphisms (SNPs) in three core genes [mammalian target of rapamycin (mTOR), mammalian lethal with sec-13 protein 8 (mLST8) and regulatory-associated protein of mTOR (RPTOR)] of the mTORC1 pathway. The associations between these SNPs and the risk of BM development were assessed. Results The AG/GG genotype of mLST8:rs26865 and TC/CC genotype of mLST8:rs3160 were associated with an increased risk of BM [hazard ratios (HR) 2.938, 95% confidence interval (CI) 1.664-5.189, p < 0.001 and HR = 2.490, 95% CI = 1.543-4.016, p < 0.001, respectively]. These risk polymorphisms had a cumulative effect on BM risk, with two risk genotypes exhibiting the highest increased risk (p < 0.001). Furthermore, these risk SNPs were associated with the lymph node metastasis (N2/3), body mass index (BMI) (≥ 25 kg/m 2), high level of squamous cell carcinoma (SCC) antigen and Ki-67 proliferation index. Moreover, patients with AG/GG genotype of mLST8:rs26865 had significantly lower median overall survival than those with AA genotype (12.1 months versus 21.6 months, p = 0.04). Conclusions Our results indicate that polymorphisms in mTORC1 pathway were significantly associated with increased risk of BM and may be valuable biomarkers to identify NSCLC patients with a high risk of BM. Keywords mTORC1 • Genetic polymorphisms • Brain metastasis • Risk • Biomarker Yiquan Xu and Yina Huang have contributed equally to the article and share the first authorship.

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Section: Discussionmentioning

confidence: 99%

Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

Huang

Weng

et al. 2019

J Cancer Res Clin Oncol

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“…We used a two‐stage approach with a discovery study followed by a replication study in the same study population to show the internal consistency in estimating cancer risk. The discovery study (Discovery set) consisted of 1,002 NSCLC patients recruited between February 2009 and February 2011 in Fudan University Shanghai Cancer Center (FUSCC), and 1,025 population‐based cancer‐free controls from the Taizhou longitudinal study (TZL) conducted at the same time period, as described previously . The replication study (Replication set) included an additional 1,333 consecutive NSCLC patients recruited between March 2011 and July 2013 from FUSCC and an additional 1,339 cancer‐free controls enrolled from TZL.…”

Section: Methodsmentioning

confidence: 99%

Genetic variants of JNK and p38α pathways and risk of non‐small cell lung cancer in an Eastern Chinese population

Jia

Zhu

Zhou

et al. 2016

Intl Journal of Cancer

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The JNK and p38α pathways play an important role in carcinogenesis. Therefore, we hypothesize that single nucleotide polymorphisms (SNPs) of genes involved in these pathways are associated with risk of lung cancer. We first selected and genotyped 11 independent SNPs of the JNK and p38α pathway-related genes in a discovery set of 1,002 non-small cell lung cancer (NSCLC) cases and 1,025 cancer-free controls of Eastern Chinese. Then, we validated those significant SNPs in a replication set of 1,333 NSCLC cases and 1,339 cancer-free controls of Eastern Chinese. Multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses were used to identify interactions between significant SNPs and other covariates. In both discovery and replication as well as their pooled analysis, carriers of GADD45G rs8252T variant genotypes had a significantly lower risk of NSCLC (adjusted OR = 0.81 and 0.79, 95% CI = 0.72-0.92 and 0.64-0.99 and p = 0.001 and 0.040 for dominant and recessive genetic models, respectively) and carriers of MAP2K7 rs3679T variant genotypes had an increased risk of NSCLC (adjusted OR = 1.19 and 1.29, 95% CI = 1.05-1.34 and 1.09-1.54 and p = 0.005 and 0.004 for dominant and recessive genetic models, respectively). Furthermore, rs8252 variant CT/TT carriers showed significantly higher levels of GADD45G mRNA expression than CC carriers in the target tissues. We observed some evidence of interactions between rs8252 genotypes and sex in NSCLC risk. These results indicate that GADD45G rs8252 and MAP2K7 rs3679 SNPs may be susceptibility biomarkers for NSCLC in Eastern Chinese populations.

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“…As previously described, exclusion criteria also included those cases who suffered from malignancies other than PCa, with a family history of PCa and those had radiotherapy or chemotherapy before recruitment. 15 In the present study, PCa were divided into two categories of highly aggressive and less aggressive as defined by the prostate-specific antigen (PSA) levels, pathological staging, and Gleason score. Tumors with PSA serum level >20 ng ml −1 , Gleason score of 7 (4 + 3), pathological stages T3 or higher were defined as highly aggressive disease, and the remainder were defined as less aggressive disease.…”

Section: Methodsmentioning

confidence: 99%

Genetic variations of the ADIPOQgene and risk of prostate cancer in Chinese Han men

Zhu

et al. 2014

Asian J Androl

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Adiponectin secreted by adipose tissue has been implicated in prostate carcinogenesis. Genetic variations in ADIPOQ are thought to influence the activity of adiponectin, thus relating to cancer occurrence. In this hospital-based case-control study of 917 prostate cancer (PCa) cases and 1036 cancer-free controls, we evaluated the association of single nucleotide polymorphisms in ADIPOQ with risk of PCa and adiponectin levels in Chinese Han men. Variants of ADIPOQ were genotyped by Taqman polymerase chain reaction method. The plasma adiponectin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in a subset of cases and controls. We found that the ADIPOQ rs3774262 variant AA genotype was associated with both decreased PCa risk [adjusted odds ratio (OR): 0.66, 95% confidence interval (CI) =0.48–0.92] and increased plasma adiponectin levels (P = 0.036 and 0.043), with significant difference by tumor grade, clinical stage, and aggressiveness. A significant interaction between ADIPOQ rs3774262 and body mass index was observed in modifying the risk of PCa (P = 6.7 × 10−3). ADIPOQ rs266729 and rs182052 were not related to PCa risk or plasma adiponectin levels. Our data support that ADIPOQ rs3774262 may affect PCa risk in combination with plasma adiponectin levels in Chinese Han men. It may contribute to the molecular basis for the association between obesity and PCa.

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Polymorphisms in the mTOR Gene and Risk of Sporadic Prostate Cancer in an Eastern Chinese Population

Cited by 29 publications

References 38 publications

Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

Effects of single-nucleotide polymorphisms in the mTORC1 pathway on the risk of brain metastasis in patients with non-small cell lung cancer

Genetic variants of JNK and p38α pathways and risk of non‐small cell lung cancer in an Eastern Chinese population

Genetic variations of the ADIPOQgene and risk of prostate cancer in Chinese Han men

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