整联蛋白α亚基1基因单核苷酸多态性与非贲门胃癌发病风险的关联性分析
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摘要
目的:探讨整联蛋白α亚基1 (ITGA1)基因单核苷酸多态性(SNP)与非贲门胃癌发病的关联性,阐明ITGA1基因多态性在非贲门胃癌发病中的作用。方法:采用病例-对照研究设计,在内蒙古自治区包头市汉族人群中选取288例非贲门胃癌患者为病例组,社区体检281人为对照组。采用TaqMan方法对2组研究对象ITGA1基因rs1862610、rs2432143和rs2447867位点的SNP进行基因分型,采用Haploview 4.0软件构建单体型,并采用非条件性Logistic回归计算比值比(OR)及其95%可信区间(95%CI),以评估各等位基因和基因型频数分布及单体型与非贲门胃癌发病风险的关联性。结果:2组研究对象ITGA1基因rs1862610、rs2432143和rs2447867位点的SNP与非贲门胃癌发病风险无关联(P>0.05);rs1862610和rs2432143位点的SNP存在强连锁不平衡(D’=1),构成单体型块,与携带单体型CT者比较,携带单体型CC者非贲门胃癌的发病风险升高(CC vs CT:OR=1.42,95%CI:1.02～1.99)。结论:在内蒙古自治区包头市汉族人群中ITGA1基因多态性可能在非贲门胃癌的发病中起一定作用,携带SNP rs1862610-rs2432143CC单体型者非贲门胃癌的发病风险升高。
Objective:To investigate the associations between single nucleotide polymorphisms(SNP)of integrinα-subunit 1(ITGA1)gene and the risk of non-cardia gastric cancer,and to elucidate the roles of ITGA1 gene polymorphisms in the risk of non-cardia gastric cancer.Methods:The case-control study design was used.A total of 288 patients with non-cardia gastric cancer were selected as case group,and 281 community physical examinees were selected as control group in Han population in Boatou City in Inner Mongolia Autonomous Region.The SNP of rs1862610,rs2432143,and rs2447867 sites of subjects in two groups were genotyped by using TaqMan method,and the haplotype was constructed by Haploview software 4.0.The odds ratio(OR)and 95% confidence intervals(95%CI)were measured by conditional Logistic regression analysis to evaluate the correlations between the frequencies of allele,genotype,and haplotypes and the susceptibility to non-cardia gastric cancer.Results:The SNP of rs1862610,rs2432143,and rs2447867 sites in ITGA1 gene were not associated with the risk of non-cardia gastric cancer(P>0.05).The SNP of rs1862610 and rs2432143 sites were in strong linkage disequilibrium(D'=1)and formed a block.Compared with those who carried haplotype CT,those who carried haplotype CC had an increasing risk of non-cardiac gastric cancer(CC vs CT:OR=1.42,95% CI:1.02-1.99).Conclusion:The ITGA1 gene polymorphisms may play a role in the risk of non-cardia gastric cancer in Han population in Baotou in Inner Mongolia Autonomous Region.The risk of non-cardia gastric cancer in the person who carries the SNP rs1862610-rs2432143 CC haplotype is increased.
Objective:To investigate the associations between single nucleotide polymorphisms(SNP)of integrinα-subunit 1(ITGA1)gene and the risk of non-cardia gastric cancer,and to elucidate the roles of ITGA1 gene polymorphisms in the risk of non-cardia gastric cancer.Methods:The case-control study design was used.A total of 288 patients with non-cardia gastric cancer were selected as case group,and 281 community physical examinees were selected as control group in Han population in Boatou City in Inner Mongolia Autonomous Region.The SNP of rs1862610,rs2432143,and rs2447867 sites of subjects in two groups were genotyped by using TaqMan method,and the haplotype was constructed by Haploview software 4.0.The odds ratio(OR)and 95% confidence intervals(95%CI)were measured by conditional Logistic regression analysis to evaluate the correlations between the frequencies of allele,genotype,and haplotypes and the susceptibility to non-cardia gastric cancer.Results:The SNP of rs1862610,rs2432143,and rs2447867 sites in ITGA1 gene were not associated with the risk of non-cardia gastric cancer(P>0.05).The SNP of rs1862610 and rs2432143 sites were in strong linkage disequilibrium(D'=1)and formed a block.Compared with those who carried haplotype CT,those who carried haplotype CC had an increasing risk of non-cardiac gastric cancer(CC vs CT:OR=1.42,95% CI:1.02-1.99).Conclusion:The ITGA1 gene polymorphisms may play a role in the risk of non-cardia gastric cancer in Han population in Baotou in Inner Mongolia Autonomous Region.The risk of non-cardia gastric cancer in the person who carries the SNP rs1862610-rs2432143 CC haplotype is increased.
引文
[1]SERVETAS S L,BRIDGE D R,MERRELL D S.Molecular mechanisms of gastric cancer initiation and progression by Helicobacter pylori[J].Curr Opin Infect Dis,2016,29(3):304-310.
[2]王琦,程慧,王柏春,等.应用基因组扫描对胃癌19号染色体进行杂合性缺失分析[J].中华医学遗传学杂志,2001,18(5):402-403.
[3]潘晓东,赵天龙飞,刘鹏霞,等.IL-17基因rs763780位点的多态性与胃癌易感性的Meta分析[J].中国肿瘤生物治疗杂志,2018,25(11):1148-1153.
[4]王倩,张小珍,王姣,等.中国人群ERCC5基因多态性与胃癌易感相关性研究的荟萃分析[J].临床检验杂志,2016,34(11):69-875.
[5]VICENTE-MANZANARES M,SANCHEZ-MADRID F.Targeting the integrin interactome in human disease[J].Curr Opin Cell Biol,2018,55:17-23.
[6]YIM D H,ZHANG Y W,EOM S Y,et al.ITGA1polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population[J].World JGastroenterol,2013,19(35):5870-5876.
[7]ZHANG B,HAO G Y,GAO F,et al.Lack of association of common polymorphisms in MUC1 gene with H.pylori infection and non-cardia gastric cancer risk in a Chinese population[J].Asian Pac J Cancer Prev,2013,14(12):7355-7358.
[8]ZHOU C J,ZHANG L W,GAO F,et al.Association analysis of common genetic variations in MUC5AC gene with the risk of non-cardia gastric cancer in a Chinese population[J].Asian Pac J Cancer Prev,2014,15(10):4207-4210.
[9]高芳,鲁林,秦金东,等.COX-2基因多态性与非贲门胃癌的发病风险关联[J].肿瘤防治研究,2015,42(5):470-473.
[10]MEI H,TU H.Vitamin C and Helicobacter pylori infection:Current knowledge and future prospects[J].Front Physiol,2018,9:1103.
[11]KWOK T,ZABLER D,URMAN S,et al.Helicobacter exploits integrin for typeⅣsecretion and kinase activation[J].Nature,2007,449(7164):862-866.
[12]BARCZYK M,CARRACEDO S,GULLBERG D.Integrins[J].Cell Tissue Res,2010,339(1):269-280.
[13]BEAUSEJOUR M,NOEL D,THIBODEAU S,et al.Integrin/Fak/Src-mediated regulation of cell survival and anoikis in human intestinalepithelial crypt cells:selective engagement and roles of PI3-K isoform complexes[J].Apoptosis,2012,17(6):566-578.
[14]FOUBERT P,VARNER J A.Integrins in tumor angiogenesis and lymphangiogenesis[J].Methods Mol Biol,2012,757:471-486.
[15]FUKUDA K,SAIKAWA Y,YAGI H,et al.Role of integrinα1 subunits in gastric cancer patients with peritoneal dissemination[J].Mol Med Rep,2012,5(2):336-340.
[16]YASOSHIMA T,DENNO R,Kawaguchi S,et al.Establishment and characterization of human gastric carcinoma lines with high metastatic potential in the liver:changes in integrin expression associated with the ability to metastasize in the liver of nude mice[J].Jpn J Cancer Res,1996,87(2):153-160.
[17]WARY K K,MARIOTTI A,ZURZOLO C,et al.A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth[J].Cell,1998,94(5):625-634.
[18]RYU B K,LEE M G,KIM N H,et al.Bidirectional alteration of Cav-1 expression is associated with mitogenic conversion of its function in gastric tumor progression[J].BMC Cancer,2017,17(1):766.
[19]YU G Z,CHEN Y,WANG J J.Over-expression of Grb2/HER2signaling in Chinese gastric cancer:their relationship with clinicopathological parameters and prognostic significance[J].J Cancer Res Clin Oncol,2009,135(10):1331-1339.
[20]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(12):1215-1218.
[2]王琦,程慧,王柏春,等.应用基因组扫描对胃癌19号染色体进行杂合性缺失分析[J].中华医学遗传学杂志,2001,18(5):402-403.
[3]潘晓东,赵天龙飞,刘鹏霞,等.IL-17基因rs763780位点的多态性与胃癌易感性的Meta分析[J].中国肿瘤生物治疗杂志,2018,25(11):1148-1153.
[4]王倩,张小珍,王姣,等.中国人群ERCC5基因多态性与胃癌易感相关性研究的荟萃分析[J].临床检验杂志,2016,34(11):69-875.
[5]VICENTE-MANZANARES M,SANCHEZ-MADRID F.Targeting the integrin interactome in human disease[J].Curr Opin Cell Biol,2018,55:17-23.
[6]YIM D H,ZHANG Y W,EOM S Y,et al.ITGA1polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population[J].World JGastroenterol,2013,19(35):5870-5876.
[7]ZHANG B,HAO G Y,GAO F,et al.Lack of association of common polymorphisms in MUC1 gene with H.pylori infection and non-cardia gastric cancer risk in a Chinese population[J].Asian Pac J Cancer Prev,2013,14(12):7355-7358.
[8]ZHOU C J,ZHANG L W,GAO F,et al.Association analysis of common genetic variations in MUC5AC gene with the risk of non-cardia gastric cancer in a Chinese population[J].Asian Pac J Cancer Prev,2014,15(10):4207-4210.
[9]高芳,鲁林,秦金东,等.COX-2基因多态性与非贲门胃癌的发病风险关联[J].肿瘤防治研究,2015,42(5):470-473.
[10]MEI H,TU H.Vitamin C and Helicobacter pylori infection:Current knowledge and future prospects[J].Front Physiol,2018,9:1103.
[11]KWOK T,ZABLER D,URMAN S,et al.Helicobacter exploits integrin for typeⅣsecretion and kinase activation[J].Nature,2007,449(7164):862-866.
[12]BARCZYK M,CARRACEDO S,GULLBERG D.Integrins[J].Cell Tissue Res,2010,339(1):269-280.
[13]BEAUSEJOUR M,NOEL D,THIBODEAU S,et al.Integrin/Fak/Src-mediated regulation of cell survival and anoikis in human intestinalepithelial crypt cells:selective engagement and roles of PI3-K isoform complexes[J].Apoptosis,2012,17(6):566-578.
[14]FOUBERT P,VARNER J A.Integrins in tumor angiogenesis and lymphangiogenesis[J].Methods Mol Biol,2012,757:471-486.
[15]FUKUDA K,SAIKAWA Y,YAGI H,et al.Role of integrinα1 subunits in gastric cancer patients with peritoneal dissemination[J].Mol Med Rep,2012,5(2):336-340.
[16]YASOSHIMA T,DENNO R,Kawaguchi S,et al.Establishment and characterization of human gastric carcinoma lines with high metastatic potential in the liver:changes in integrin expression associated with the ability to metastasize in the liver of nude mice[J].Jpn J Cancer Res,1996,87(2):153-160.
[17]WARY K K,MARIOTTI A,ZURZOLO C,et al.A requirement for caveolin-1 and associated kinase Fyn in integrin signaling and anchorage-dependent cell growth[J].Cell,1998,94(5):625-634.
[18]RYU B K,LEE M G,KIM N H,et al.Bidirectional alteration of Cav-1 expression is associated with mitogenic conversion of its function in gastric tumor progression[J].BMC Cancer,2017,17(1):766.
[19]YU G Z,CHEN Y,WANG J J.Over-expression of Grb2/HER2signaling in Chinese gastric cancer:their relationship with clinicopathological parameters and prognostic significance[J].J Cancer Res Clin Oncol,2009,135(10):1331-1339.
[20]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(12):1215-1218.