The single nucleotide variant rs2868371 associates with the risk of mortality in non-small cell lung cancer patients: A multicenter prospective validation

Enguix-Riego, María del Valle; Cacicedo, Jon; León, B.D. Delgado; Gomez, Juan Povedano; Rivera, Daniel; Pérez, Manuel; Praena-Fernández, Juan Manuel; Carmona, Gerardo Sanchez; Campo, Eleonor Rivin del; Gordillo, María Dolores Gordillo; Guerra, José Luis López

doi:10.1016/j.radonc.2019.03.025

Cited by 8 publications

(6 citation statements)

References 40 publications

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“…The prognostic impact of polymorphisms of various cancer‐related genes has been reported in NSCLC patients treated with RT 18–20 . However, the impact of GLUT1 polymorphisms on the prognosis of patients with stage III NSCLC treated with RT has not been reported, even though metabolic reprogramming is a common phenomenon in NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of genetic variants in GLUT1 in stage III non‐small cell lung cancer treated with radiotherapy

et al. 2021

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Background To examine the impact of polymorphisms of glucose transporter 1 (GLUT1) gene on the prognosis of patients with stage III non‐small cell lung cancer (NSCLC) who received radiotherapy. Methods Five single nucleotide polymorphisms (SNPs) (rs4658C>G, rs1385129G>A, rs3820589A>T, rs3806401A>C and rs3806400C>T) in GLUT1 gene were evaluated in 90 patients with pathologically confirmed stage III NSCLC. A total of 21 patients were treated with radiotherapy alone, 25 with sequential chemoradiotherapy, and 44 with concurrent chemoradiotherapy. The association of the genetic variations of five SNPs with overall survival (OS) and progression‐free survival (PFS) was analyzed. Results Two SNPs (rs1385129 and rs3806401) were significant risk factors for OS. Three SNPs (rs1385129, rs3820589 and rs3806401) were in linkage disequilibrium. In Cox proportional hazard models, GAA haplotype was a good prognostic factor for OS (hazard ratio [HR] = 0.57, 95% confidence interval [CI]: 0.39–0.81, p = 0.002) and PFS (HR = 0.68, 95% CI: 0.47–0.99, p = 0.043), compared to variant haplotypes. The GAA/GAA diplotype was observed in 46.7% of patients; these patients showed significantly better OS (HR = 0.38, 95% CI: 0.22–0.65, p < 0.001) and PFS (HR = 0.51, 95% CI: 0.31–0.85, p = 0.009) compared to those with other diplotypes. Conclusions These results suggest that polymorphisms of GLUT1 gene could be used as a prognostic marker for patients with stage III NSCLC treated with radiotherapy.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of genetic variants in GLUT1 in stage III non‐small cell lung cancer treated with radiotherapy

et al. 2021

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“…Recently, it has been reported that GR binds to TEAD4 promoter and promotes TEAD4 transcription during adipogenesis 42 . Enguix‐Riego et al 43 found that HSPB1 rs2868371 A > G promotes HSPB1 transcriptional level by promoting GR bind to the HSPB1 promoter region. Similarly, we obtained that the alteration from A to G at rs7783388 may modulate the binding affinity of GR to MAGI2‐AS3 promoter region.…”

Section: Discussionmentioning

confidence: 99%

MAGI2‐AS3 rs7783388 polymorphism contributes to colorectal cancer risk through altering the binding affinity of the transcription factor GR to the MAGI2‐AS3 promoter

Yang

et al. 2020

Clinical Laboratory Analysis

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Background It has been indicated that the single nuclear polymorphisms (SNPs) in the long noncoding RNA (lncRNA) have association with colorectal cancer (CRC) susceptibility. Methods We enrolled 1078 cases with CRC and 1175 age‐ and gender‐matched cancer‐free controls to explore whether the polymorphisms in MAGI2‐AS3 have associations with CRC risk. qRT‐PCR, expression quantitative trait loci (eQTL) analyses, dual‐luciferase reporter assay, chromatin immunoprecipitation (ChIP), flow cytometry, and transwell assays were performed to explore the specific mechanisms in which MAGI2‐AS3 rs7783388 variation influenced the tumorigenesis of CRC. Results Subjects carrying rs7783388 GG genotype presented a higher risk of CRC compared with the AG/AA genotypes. Mechanistically, we found that the functional genetic variant of rs7783388 A > G decreased binding affinity of transcription factor glucocorticoid receptor (GR) to the MAGI2‐AS3 promoter, resulting in decreased transcriptional activity that subsequently downregulated MAGI2‐AS3 expression. Furthermore, functional experiments elucidated that MAGI2‐AS3 overexpression suppressed CRC cell proliferation, migration, and invasion capacities, arrested cell cycle at G0/G1 phase, and promoted cell apoptosis. Conclusion Taken together, our study demonstrated that the potential function of MAGI2‐AS3 as a tumor suppressor for CRC, and the MAGI2‐AS3 rs7783388 polymorphism is associated with the increased susceptibility to CRC by altering the binding ability of GR to the MAGI2‐AS3 promoter.

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“…The difference in individual response and survival in NSCLC patients suggests that genetic factors may play a role in treatment response and cancer progression 4 . Genetic variants have proven to be important predictors of cancer development, of which single‐nucleotide polymorphisms (SNPs), the major forms of genetic variations, have been most widely studied 5–7 . Genome‐wide association studies (GWASs), complemented by pathway‐based studies, have identified a series of genetic variants associated with lung cancer risk and survival 8–10 .…”

Section: Introductionmentioning

confidence: 99%

“…4 Genetic variants have proven to be important predictors of cancer development, of which singlenucleotide polymorphisms (SNPs), the major forms of genetic variations, have been most widely studied. [5][6][7] Genome-wide association studies (GWASs), complemented by pathway-based studies, have identified a series of genetic variants associated with lung cancer risk and survival. [8][9][10] Cancer immune evasion is one of the hallmarks of carcinogenesis, and immune pathways such as the PD-1/PDL1 pathway have been reported to affect lung cancer development by suppressing T-cell function and driving immune escape.…”

Section: Introductionmentioning

confidence: 99%

Potentially functional genetic variants of VAV2 and PSMA4 in the immune‐activation pathway and non‐small cell lung cancer survival

Bai

Zheng

Cheng

et al. 2022

The Journal of Gene Medicine

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Background: Lung cancer has the highest mortality among cancers, represented by a low 5-year survival rate. The function of the immune system has a profound influence on the development and progression of lung cancer. Thus genetic variants of the immune-related genes may serve as potential predictors of non-small cell lung cancer (NSCLC) survival. Methods:In the present study, we conducted a two-stage survival analysis in 1,531 NSCLC patients and assessed the associations between genetic variants in the immune-activation gene set and the overall survival (OS) of NSCLC patients. The validated variants were further subjected to functional annotation and in vitro experiments.Results: We identified 25 SNPs spanning six loci associated with NSCLC OS after multiple-testing corrections in all datasets, in which two variants, PSMA4 rs12901682 A > C and VAV2 rs12002767 C > T, were shown to potentially affect lung cancer OS by cis-regulating the expression of the corresponding genes [(HR (95% CI) = 0.76 (0.65-0.89) and 1.36 (1.12-1.65), p = 4.29 Â 10 À4 and 0.002, respectively]. Conclusion:Our findings provide new insights into the role of genetic variants in the immune-activation pathway genes in lung cancer progression.

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The single nucleotide variant rs2868371 associates with the risk of mortality in non-small cell lung cancer patients: A multicenter prospective validation

Cited by 8 publications

References 40 publications

Prognostic significance of genetic variants in GLUT1 in stage III non‐small cell lung cancer treated with radiotherapy

Prognostic significance of genetic variants in GLUT1 in stage III non‐small cell lung cancer treated with radiotherapy

MAGI2‐AS3 rs7783388 polymorphism contributes to colorectal cancer risk through altering the binding affinity of the transcription factor GR to the MAGI2‐AS3 promoter

Potentially functional genetic variants of VAV2 and PSMA4 in the immune‐activation pathway and non‐small cell lung cancer survival

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