PRKAα1基因多态性与东亚人群胃癌易感性研究的meta分析

doi:10.3969/j.issn.1004-616x.2018.02.008

摘要/Abstract

摘要： 目的：综合评价PRKAα1基因5个单核苷酸多态性位点rs13361707C > T、rs10074991G > A、rs154268T > C、rs3805486T > C、rs6882903C > A多态性与东亚人群胃癌易感性的关系。方法：检索PubMed、中国知网、万方、维普等数据库收集关于PRKAα1基因多态性与胃癌易感性研究的文献。利用STATA 12.0软件计算比值比（OR）和95%可信区间（95% CI），进行敏感性分析和发表偏倚的检测。结果：rs13361707C > T位点纳入9项研究，该位点多态性与东亚人群胃癌的易感性无统计学相关性。亚组分析显示，显性模型的合并OR=0.687，95% CI （0.614~0.769），P=0.000；隐性模型的合并OR=0.662，95% CI （0.594~0.737），P=0.000；加性模型的合并OR=0.553，95% CI （0.484~0.632），P=0.000；共显性模型的合并OR=0.766，95% CI （0.682~0.859），P=0.000；该结果提示在4种模型下韩国人群患胃癌风险降低。rs10074991G > A位点纳入3项研究，meta分析结果显示，显性模型的合并OR=0.590，95% CI （0.490~0.700），P=0.000；隐性模型的合并OR=0.637，95% CI （0.535~0.759），P=0.000；加性模型的合并OR=0.478，95% CI （0.385~0.593），P=0.000；共显性模型的合并OR=0.651，95% CI （0.541~0.784），P=0.000；该结果提示在4种模型下东亚人群患胃癌风险降低。亚组分析结果显示，在4种模型下韩国人群患胃癌风险降低。除隐性模型外，在其余3种模型下中国人群患胃癌风险降低。rs154268T > C、rs3805486T > C、rs6882903C > A这3个位点分别纳入2项研究，除隐性模型外，rs154268T > C位点在3种模型下韩国人群患胃癌风险增加，rs3805486T > C位点在4种模型下韩国人群患胃癌风险降低，rs6882903C > A位点在显性和加性模型下韩国人群患胃癌风险增加。Begg’s检测未发现发表偏倚（P > 0.05），敏感性分析说明上述结果具有稳定性。结论：PRKAα1基因rs10074991G > A、rs154268T > C、rs3805486T > C、rs6882903C > A位点多态性与胃癌的易感性有关。

关键词: 胃癌, PRKAα1, 单核苷酸多态性, meta分析

Abstract: OBJECTIVE: To investigate the correlation of five single nucleotide polymorphisms in the PRKAα1 gene(rs13361707C > T,rs10074991G > A,rs154268T > C,rs3805486T > C and rs6882903C > A) with gastric cancer risk in an East Asian population. METHODS: Publications of correlation between PRKAα1 gene polymorphisms and gastric cancer were searched from PubMed,China National Knowledge Infrastructure (CNKI),Chinese Wan Fang database and Database of Chinese Scientific and Technical Periodicals (VIP). The odds ratios (OR) and 95% confidence intervals (95% CI),and sensitivity and publication bias were analyzed by STATA 12.0 software. RESULTS: The rs13361707C > T polymorphism analysis was mentioned in 9 studies. There was no significant association between rs13361707C > T polymorphism and gastric cancer risk in East Asian populations. The result of subgroup-analysis demonstrates:dominant model,OR=0.687,95% CI(0.614-0.769),P=0.000;recessive model,OR=0.662,95% CI(0.594-0.737),P=0.000; Addictive Model,OR=0.553,95% CI(0.484-0.632),P=0.000;codominant model,OR=0.766,95% CI(0.682-0.859), P=0.000;The subgroup analysis showed that this locus was associated with the decreased risk of gastric cancer in a Korean population under the four models. The rs10074991G > A polymorphism analysis was performed in 3 studies. The result of meta-analysis demonstrates:Dominant model,OR=0.590,95% CI(0.490-0.700),P=0.000;recessive model,OR=0.637,95% CI(0.535-0.759),P=0.000;addictive model,OR=0.478,95% CI(0.385-0.593),P=0.000; codominant model,OR=0.651,95% CI(0.541-0.784),P=0.000. The results show that this locus was associated with the decreased risk of gastric cancer in East Asian populations under the four genetic models. The subgroup analysis show that this locus was associated with the decreased risk of gastric cancer in Korean populations under the four genetic models. In addition to the recessive model,this locus was associated with the decreased risk of gastric cancer in Chinese populations under other three models. Three SNPs of rs154268T > C,rs3805486T > C,rs6882903C > A analysis were performed in 2 published studies. In addition to the recessive model,the rs154268T > C polymorphism was associated with the increased risk of gastric cancer in Korean populations under other three models. rs3805486T > C polymorphism was associated with the decreased risk of gastric cancer in Korean populations under the four genetic models. The rs6882903C > A polymorphism was associated with the increased risk of gastric cancer in Korean populations under the dominance and additive models. Begg's test found no publication bias (P > 0.05),sensitivity analysis showed that the above results were stable. CONCLUSION: The rs10074991G > A,rs154268T > C,rs3805486T > C and rs6882903C > A polymorphisms in PRKAα1 gene were significantly correlated with increased gastric cancer risk.

Key words: gastric cancer, PRKAα1, single nucleotide polymorphis, meta-analysis

中图分类号:

R730.2

杨美娟, 张东, 樊文静, 张敏, 尤崇革. PRKAα1基因多态性与东亚人群胃癌易感性研究的meta分析[J]. 癌变·畸变·突变, 2018, 30(2): 120-125,154.

YANG Meijuan, ZHANG Dong, FAN Wenjing, ZHANG Min, YOU Chongge. Correlation of PRKAα1 gene polymorphisms with gastric cancer risk in an East Asian population: A meta-analysis[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(2): 120-125,154.

参考文献

[1] FERLAY J,SOERJOMATARAM I,DIKSHIT R,et al. Cancer incidence and mortality worldwide:sources,methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer,2015,136(5):359-386.
[2] 吴迪. PSCA、PLCE1、PRKAα1基因多态性及幽门螺旋杆菌感染与胃癌易感性的关系[D]. 兰州:兰州大学,2014.
[3] GLEASON C E,LU D,WITTERS L A,et al. The role of AMPK and mTOR in nutrient sensing in pancreatic beta-cells[J]. J Biol Chem,2007,2(82):10341-10351.
[4] HOU L,LI Y,SONG H,et al. Protective macroautophagy is involved in vitamin E succinate effects on human gastric carcinoma cell line SGC-7901 by Inhibiting mTOR axis phosphorylation[J]. PLoS One,2015,10:0132829.
[5] LI S,ZHOU T,LI C,et al. High metastaticgastric and breast cancer cells consume oleic acid in an AMPK dependent manner[J]. PLoS One,2014,9:97330.
[6] KIM Y H,LIANG H,LIU X,et al. AMPKalpha modulation in cancer progression:multilayer integrative analysis of the whole transcriptome in Asian gastric cancer[J]. Cancer Res,2012,72:2512-2521.
[7] OBBA S,HIZIR Z,BOYER L,et al. The PRKAα1/AMPKalpha1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is apotential target in CMML[J]. Autophagy,2015,11:1114-1129.
[8] CAI M,DAI S,CHEN W,et al. Environmental factors,seven GWAS-identified susceptibility loci,and risk of gastric cancer and its precursors in a Chinese population[J]. Cancer Med, 2017,6(3):708-720.
[9] 张永菊,张春艳,于新娟,等. PRKAα1和UNC5CL基因多态性与胃癌易感性的关系[J]. 中国临床医生杂志,2016,10:21-25.
[10] EOM S Y,HONG S M,YIM D H,et al. Additive interactions between PRKAA1 polymorphisms and Helicobacter pylori CagA infection associated with gastric cancer risk in Koreans[J]. Cancer Med,2016,5(11):3326-3335.
[11] DONG Y,CHEN J,CHEN Z,et al. Evaluating the association of eight polymorphisms with cancer susceptibility in a Han Chinese population[J]. PLoS One,2015,10(7):0132797.
[12] LI M,HUANG L,QIU H,et al. Helicobacter pylori infection synergizes with three inflammation-related genetic variants in the GWASs to increase risk of gastric cancer in a Chinese population[J]. PLoS One,2013,8(9):74976.
[13] SONG H R,KIM H N,KWEON S S,et al. Genetic variations in the PRKAα1 and ZBTB20 genes and gastric cancer susceptibility in a Korean population[J]. Mol Carcinog,2013,52(1):155-160.
[14] SHI Y,HU Z,WU C,et al. A genome-wide association study identifies new susceptibility loci for non-cardia gastric cancer at 3q13.31 and 5p13.1[J]. Nat Genet,2011,43:1215-1218.
[15] MATTHEW F C,FRANCIS R,MELISSA S H,et al. Structural basis for AMPK activation:natural and synthetic ligands regulate kinase activity from opposite poles by different molecular mechanisms[J]. Structure,2014,22(8):1161-1172.
[16] 王晓斌,刘国仰. 有关内含子功能研究的新进展[J]. 中华医学遗传学杂志,2000,17(3):211-212.
[17] MOUNT S,HENIKOFF S. Gene organization:nested genes take flight[J]. Curr Biol,1993,3(6):372-374.
[18] TIAN C,CHEN Z,MA X,et al. Comparison of genetic variants in cancer-related genes between Chinese Hui and Han populations[J]. PLoS One,2015,10(12):0145170.