External Replication of Urinary Bladder Cancer Prognostic Polymorphisms in the UK Biobank

Lipunova, N. A.; Wesselius, Anke; Cheng, Kar Keung; Schooten, Frederik J. van; Cazier, Jean‐Baptiste; Bryan, Richard T.

doi:10.3389/fonc.2019.01082

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…Also, the rs2042329 T allele was related to significantly higher expression levels of CWC27 among tumor tissues in low- or high-grade non-muscle-invasive tumors, rather than in the adjacent normal tissues and invasive tumors. A replication study in the UK population [ 33 ] also showed that rs2042329 was linked to an increased risk of urinary BCa recurrence.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population

Guo

2022

BioMed Research International

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Bladder cancer (BCa) is an increasingly severe clinical and public health issue. Therefore, we aim to investigate BCa susceptibility loci in the Chinese population. In this study, 487 BCa patients and 563 controls were recruited from the First Affiliated Hospital of China Medical University from July 2015 to September 2020. A total of ten single-nucleotide polymorphisms (SNPs) in solute carrier family 15 member 1 (SLC15A1), CWC27 spliceosome associated cyclophilin (CWC27), or UDP glucuronosyltransferase family 1 member A3 (UGT1A3) genes were genotyped. The associations between the candidate SNPs and BCa were analyzed using genotype and haplotype analysis. The results demonstrated that Rs4646227 of SLC15A1 has a significant association with BCa. The patients with CG (OR =2.513, p < 0.05 ) and GG (OR =2.859, p < 0.05 ) genotypes had an increasing risk of BCa compared with the CC genotype. For the CWC27 gene, genotypic frequency analysis revealed that the GT or TT genotype of rs2042329 and the CT or TT genotype of rs1870437 were more frequent in BCa patients than those in the control group, indicating that these genotypes were associated with a higher risk of BCa (all p < 0.05 ). Haplotypes of SLC15A1, UGT1A3, and CWC27 genes found that the C-C-C haplotype of SLC15A1 was associated with a lower risk of BCa while the C-G-C haplotype was associated with a higher risk. For the UGT1A3 gene, a moderate protective effect was observed with the most frequent T-T-C haplotype, and for the CWC27 gene, most of the haplotypes showed no association with BCa, except the G-G-C-T haplotype (order of SNPs: rs2042329-rs7735338-rs1870437-rs2278351, OR =0.81, p =0.038). In sum, this study indicated that rs2042329 and rs1870437 in the CWC27 gene and rs4646227 in the SLC15A1 gene are independent indicators for BCa risk in Chinese people. Further large-scale studies are required to validate these findings. Also, this study provided the theoretical basis for developing new therapeutic drug targeting of BCa.

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Section: Discussionmentioning

confidence: 99%

Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population

Guo

2022

BioMed Research International

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“…FKBP1A has also been reported to play a role in promoting tumor progression. Zhang et al (2019) found that FKBP1A affected the proliferation and migration of prostate cancer cells ( Lipunova et al, 2019 ). Romano et al (2008) found that knockdown of FKBP1A can activate the TGF-β signaling pathway in chronic lymphocytic leukemia cells ( Zhang et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

The Construction of a Prognostic Model Based on a Peptidyl Prolyl Cis–Trans Isomerase Gene Signature in Hepatocellular Carcinoma

Shi

Zhong

et al. 2021

Front. Genet.

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Objective: The aim of the present study was to construct a prognostic model based on the peptidyl prolyl cis–trans isomerase gene signature and explore the prognostic value of this model in patients with hepatocellular carcinoma.Methods: The transcriptome and clinical data of hepatocellular carcinoma patients were downloaded from The Cancer Genome Atlas and the International Cancer Genome Consortium database as the training set and validation set, respectively. Peptidyl prolyl cis–trans isomerase gene sets were obtained from the Molecular Signatures Database. The differential expression of peptidyl prolyl cis–trans isomerase genes was analyzed by R software. A prognostic model based on the peptidyl prolyl cis–trans isomerase signature was established by Cox, Lasso, and stepwise regression methods. Kaplan–Meier survival analysis was used to evaluate the prognostic value of the model and validate it with an independent external data. Finally, nomogram and calibration curves were developed in combination with clinical staging and risk score.Results: Differential gene expression analysis of hepatocellular carcinoma and adjacent tissues showed that there were 16 upregulated genes. A prognostic model of hepatocellular carcinoma was constructed based on three gene signatures by Cox, Lasso, and stepwise regression analysis. The Kaplan–Meier curve showed that hepatocellular carcinoma patients in high-risk score group had a worse prognosis (p < 0.05). The receiver operating characteristic curve revealed that the area under curve values of predicting the survival rate at 1, 2, 3, 4, and 5 years were 0.725, 0.680, 0.644, 0.630, and 0.639, respectively. In addition, the evaluation results of the model by the validation set were basically consistent with those of the training set. A nomogram incorporating clinical stage and risk score was established, and the calibration curve matched well with the diagonal.Conclusion: A prognostic model based on 3 peptidyl prolyl cis–trans isomerase gene signatures is expected to provide reference for prognostic risk stratification in patients with hepatocellular carcinoma.

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“…New strategies for disease prevention have comprised the exploration of gene-environment interactions and the attenuation of genetic risk via health-promoting factors (21)(22)(23). Previous studies have investigated the interaction between the genetic factors of AD and environmental variables, such as diet, alcohol, smoking, and pollutants (24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Education counteracts the genetic risk of Alzheimer’s disease without an interaction effect

Li,

Zhang,

Zhang

et al. 2023

Front. Public Health

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BackgroundAlzheimer’s disease (AD) is a major cause of disability and mortality in older adults. This study aimed to investigate the association of AD with education and genetic factors.MethodsWe conducted a prospective cohort study using data from the UK Biobank. Genetic risk was assessed using a polygenic risk score for AD. The educational level was categorized as either low, intermediate, or high. AD was defined using the International Classification of Diseases and Related Health Problems, 10th revision. Logistic regression models were used to investigate the independent and combined effects of genetic factors and educational levels on the risk of AD.ResultsWe included 318,535 participants in this study (age: 56.53 ± 8.09 years; male: 44.81%). Compared with a low genetic risk, a high genetic risk was associated with a significantly greater risk of AD (OR = 7.09, 95% CI: 6.09–8.26). A high educational level was associated with a 30% lower risk of AD compared with a low educational level (OR = 0.70, 95% CI: 0.60–0.81). Combining genetic risk and education categories, individuals with a low genetic risk and high educational level had a more than 90% (OR = 0.09, 95% CI: 0.05–0.16) lower risk of AD compared to those with a high genetic risk and low educational level. There was no significant interaction between genetic risk and educational level regarding AD risk (p for interaction = 0.359).ConclusionEducation counteracts the genetic risk of AD, without an interaction effect. Increasing education to reduce the incidence of AD is of same importance across individuals with different genetic risk.

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External Replication of Urinary Bladder Cancer Prognostic Polymorphisms in the UK Biobank

Cited by 4 publications

References 24 publications

Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population

Susceptibility Loci in SLC15A1, UGT1A3, and CWC27 Genes Associated with Bladder Cancer in the Northeast Chinese Population

The Construction of a Prognostic Model Based on a Peptidyl Prolyl Cis–Trans Isomerase Gene Signature in Hepatocellular Carcinoma

Education counteracts the genetic risk of Alzheimer’s disease without an interaction effect

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