Cargando…

Do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review

BACKGROUND: Currently, several studies have demonstrated that PRKAA1 polymorphisms conduce to the development of cancer. PRKAA1 gene encodes the AMP-activated protein kinase summit-α1, and plays an important role in cell metabolism. Thus, we performed a systematic review and meta-analysis of all enr...

Descripción completa

Detalles Bibliográficos
Autores principales: Meng, Jialin, Fan, Xinyao, Zhang, Meng, Hao, Zongyao, Liang, Chaozhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194619/
https://www.ncbi.nlm.nih.gov/pubmed/30340465
http://dx.doi.org/10.1186/s12881-018-0704-8
_version_ 1783364261598199808
author Meng, Jialin
Fan, Xinyao
Zhang, Meng
Hao, Zongyao
Liang, Chaozhao
author_facet Meng, Jialin
Fan, Xinyao
Zhang, Meng
Hao, Zongyao
Liang, Chaozhao
author_sort Meng, Jialin
collection PubMed
description BACKGROUND: Currently, several studies have demonstrated that PRKAA1 polymorphisms conduce to the development of cancer. PRKAA1 gene encodes the AMP-activated protein kinase summit-α1, and plays an important role in cell metabolism. Thus, we performed a systematic review and meta-analysis of all enrolled eligible case-control studies to obtain a precise correlation between PRKAA1 polymorphism and cancer susceptibility. METHODS: Extensive retrieve was performed in Web of Science, Google Scholar, PubMed, EMbase, CNKI and Wanfang databases up to August 26, 2018. Odds ratios (ORs) and 95% CIs were performed to evaluate the overall strength of the associations in five models, as well as in subgroup analyses, stratified by ethnicity, cancer type or source of control. Q-test, Egger’s test and Begg’s funnel plot were applied to evaluate the heterogeneity and publication bias. In-silico analysis was performed to demonstrate the relationship of PRKAA1 expression correlated with cancer tissues and survival time. RESULTS: Twenty-two case-control studies from 14 publications were enrolled, with 17,068 cases and 20,871 controls for rs13361707, and 2514 cases and 3193 controls for rs10074991. Overall, we identified that the PRKAA1 rs13361707 polymorphism is not significantly associated with cancer susceptibility under all five genetic models. For rs10074991, we revealed a significant decrease risk in allelic comparison model (B vs. A: OR = 0.774, 95% CI = 0.642–0.931, P(Adjust) = 3.376*10(− 2)), heterozygote comparison model (BA vs. AA: OR = 0.779 95%CI = 0.691–0.877, P(Adjust) = 9.86*10(− 10);), and dominant genetic model (BB + BA vs. AA: OR = 0.697 95%CI = 0.533–0.912, P(Adjust) = 4.211*10(− 2);). Evidence from TCGA database and GTEx projects indicated that the expression of PRKAA1 in gastric cancer tissue is higher, compared to normal stomach tissue, as well as it in breast cancer and esophageal squamous cell carcinoma. However, the Kaplan-Meier estimate showed that there is no significant difference of OS and RFS between the low and high PRKAA1 TPM groups in gastric cancer, breast cancer, and esophageal carcinoma. CONCLUSIONS: To sum up, PRKAA1 rs13361707 polymorphism is not participant with the increased risk of cancer, while the A allele of PRKAA1 rs10074991 revealed a significant decrease risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0704-8) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6194619
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-61946192018-10-25 Do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review Meng, Jialin Fan, Xinyao Zhang, Meng Hao, Zongyao Liang, Chaozhao BMC Med Genet Research Article BACKGROUND: Currently, several studies have demonstrated that PRKAA1 polymorphisms conduce to the development of cancer. PRKAA1 gene encodes the AMP-activated protein kinase summit-α1, and plays an important role in cell metabolism. Thus, we performed a systematic review and meta-analysis of all enrolled eligible case-control studies to obtain a precise correlation between PRKAA1 polymorphism and cancer susceptibility. METHODS: Extensive retrieve was performed in Web of Science, Google Scholar, PubMed, EMbase, CNKI and Wanfang databases up to August 26, 2018. Odds ratios (ORs) and 95% CIs were performed to evaluate the overall strength of the associations in five models, as well as in subgroup analyses, stratified by ethnicity, cancer type or source of control. Q-test, Egger’s test and Begg’s funnel plot were applied to evaluate the heterogeneity and publication bias. In-silico analysis was performed to demonstrate the relationship of PRKAA1 expression correlated with cancer tissues and survival time. RESULTS: Twenty-two case-control studies from 14 publications were enrolled, with 17,068 cases and 20,871 controls for rs13361707, and 2514 cases and 3193 controls for rs10074991. Overall, we identified that the PRKAA1 rs13361707 polymorphism is not significantly associated with cancer susceptibility under all five genetic models. For rs10074991, we revealed a significant decrease risk in allelic comparison model (B vs. A: OR = 0.774, 95% CI = 0.642–0.931, P(Adjust) = 3.376*10(− 2)), heterozygote comparison model (BA vs. AA: OR = 0.779 95%CI = 0.691–0.877, P(Adjust) = 9.86*10(− 10);), and dominant genetic model (BB + BA vs. AA: OR = 0.697 95%CI = 0.533–0.912, P(Adjust) = 4.211*10(− 2);). Evidence from TCGA database and GTEx projects indicated that the expression of PRKAA1 in gastric cancer tissue is higher, compared to normal stomach tissue, as well as it in breast cancer and esophageal squamous cell carcinoma. However, the Kaplan-Meier estimate showed that there is no significant difference of OS and RFS between the low and high PRKAA1 TPM groups in gastric cancer, breast cancer, and esophageal carcinoma. CONCLUSIONS: To sum up, PRKAA1 rs13361707 polymorphism is not participant with the increased risk of cancer, while the A allele of PRKAA1 rs10074991 revealed a significant decrease risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12881-018-0704-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-19 /pmc/articles/PMC6194619/ /pubmed/30340465 http://dx.doi.org/10.1186/s12881-018-0704-8 Text en © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Meng, Jialin
Fan, Xinyao
Zhang, Meng
Hao, Zongyao
Liang, Chaozhao
Do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review
title Do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review
title_full Do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review
title_fullStr Do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review
title_full_unstemmed Do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review
title_short Do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review
title_sort do polymorphisms in protein kinase catalytic subunit alpha-1 gene associated with cancer susceptibility? a meta-analysis and systematic review
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194619/
https://www.ncbi.nlm.nih.gov/pubmed/30340465
http://dx.doi.org/10.1186/s12881-018-0704-8
work_keys_str_mv AT mengjialin dopolymorphismsinproteinkinasecatalyticsubunitalpha1geneassociatedwithcancersusceptibilityametaanalysisandsystematicreview
AT fanxinyao dopolymorphismsinproteinkinasecatalyticsubunitalpha1geneassociatedwithcancersusceptibilityametaanalysisandsystematicreview
AT zhangmeng dopolymorphismsinproteinkinasecatalyticsubunitalpha1geneassociatedwithcancersusceptibilityametaanalysisandsystematicreview
AT haozongyao dopolymorphismsinproteinkinasecatalyticsubunitalpha1geneassociatedwithcancersusceptibilityametaanalysisandsystematicreview
AT liangchaozhao dopolymorphismsinproteinkinasecatalyticsubunitalpha1geneassociatedwithcancersusceptibilityametaanalysisandsystematicreview